Clinical practice guidelines: Type 1 diabetes in children and adolescents

Transcription

Clinical practice guidelines:
Type 1 diabetes in children
and adolescents
Prepared by the Australasian Paediatric Endocrine Group for the
Department of Health and Ageing
APPROVED BY THE NHMRC ON 9 MARCH 2005
©
Commonwealth of Australia 2005
ISBN Online: 0 642 82630 7
Electronic publications
This work is copyright. You may download, display, print and reproduce this material in
unaltered form only (retaining this notice) for your personal, non-commercial use or use
within your organisation. Apart from any use as permitted under the Copyright Act 1968, all
other rights are reserved. Requests for further authorisation should be directed to the
Commonwealth Copyright Administration, Attorney-General’s Department, Robert Garran
Offices, National Circuit, Canberra ACT 2600 or posted at http://www.ag.gov.au/cca
These guidelines were approved by the National Health and Medical Research Council
(NHMRC) at its 156th Session on 9 March 2005, under Section 14A of the National Health
and Medical Research Council Act 1992. Approval for the guidelines by NHMRC is granted
for a period not exceeding five years, at which date the approval expires. The NHMRC
expects that all guidelines will be reviewed no less than once every five years. Readers
should check with the Department of Health and Ageing for any reviews or updates of these
guidelines.
Disclaimer
This document is a general guide to appropriate practice, to be followed subject to the
clinician’s judgement and the patient’s preference in each individual case.
The guidelines are designed to provide information to assist decision-making and are based
on the best evidence available at the time of compilation.
These guidelines can be downloaded from the National Health and Medical Research Council
website: www.nhmrc.gov.au/publications.
i
Table of Contents
Table of Contents .............................................................................................................. i
Tables ............................................................................................................................... x
Figures .............................................................................................................................. x
Introduction ....................................................................................................................... 1
Background....................................................................................................................... 1
Rationale for the Guidelines .............................................................................................. 1
Scope of the Guidelines..................................................................................................... 1
Areas beyond the remit of the guidelines........................................................................ 1
Target Audience................................................................................................................ 2
Guidelines Development Process ...................................................................................... 2
Guidelines writing committee ........................................................................................ 2
Review of existing guidelines ......................................................................................... 2
Formulation of Clinical Questions..................................................................................... 2
Locating the Evidence ....................................................................................................... 2
Levels of Evidence and Critical Appraisal ......................................................................... 3
Economic Considerations.................................................................................................. 6
Guidelines Review Date .................................................................................................... 6
Structure of the Guidelines ................................................................................................ 6
Overview of the Guidelines ............................................................................................... 6
Consultation and Peer-review Process ............................................................................... 7
Dissemination ................................................................................................................... 7
Legal Considerations......................................................................................................... 7
Reference List ................................................................................................................... 7
List of Abbreviations ....................................................................................................... 8
Acknowledgements .......................................................................................................... 9
Executive Summary of Recommendations and Principles ..................................... 10
1. Definition, Epidemiology and Classification............................................................... 10
2. Phases of Diabetes...................................................................................................... 10
3. Medical Management ................................................................................................. 11
4. Insulin Preparations and Storage................................................................................. 11
5. Insulin Regimens and Delivery................................................................................... 12
6. Glycaemic Control ..................................................................................................... 13
7. Nutrition..................................................................................................................... 13
8. Physical Activity ........................................................................................................ 14
9. Diabetic Ketoacidosis................................................................................................. 14
10. Surgery and Fasting.................................................................................................. 15
11. Sick Day Management.............................................................................................. 15
12. Hypoglycaemia ........................................................................................................ 16
13. Psychosocial Aspects................................................................................................ 17
14. Diabetes Complications ............................................................................................ 17
15. Other Complications and Associated Conditions ...................................................... 18
16. Foot Care.................................................................................................................. 18
17. Dental Health ........................................................................................................... 18
18. Adolescent Health Issues .......................................................................................... 18
19. School ...................................................................................................................... 19
20. Diabetes Camps for Children and Adolescents.......................................................... 20
21. Travelling and Holidays ........................................................................................... 20
Table of Contents
Australian Clinical Practice Guidelines: Type 1 Diabetes in Children and Adolescents
ii
22. Complementary and Alternative Medicine................................................................ 20
Reference List ................................................................................................................. 21
Chapter 1: Definition, Epidemiology and Classification......................................... 10
Definition........................................................................................................................ 26
Epidemiology.................................................................................................................. 26
Classification .................................................................................................................. 28
Clinical Staging of Diabetes ............................................................................................ 28
Aetiologic Classification of Diabetes............................................................................... 29
Diagnostic Criteria for Diabetes in Childhood and Adolescence ...................................... 31
Oral Glucose Tolerance Test (OGTT) ............................................................................. 32
Interpretation of OGTT ................................................................................................... 32
Intravenous Glucose Tolerance Test (IVGTT)................................................................. 33
Metabolic Syndrome ....................................................................................................... 33
Type 2 Diabetes .............................................................................................................. 34
Screening for Type 2 Diabetes......................................................................................... 35
Other Types of Diabetes.................................................................................................. 35
Maturity Onset Diabetes of the Young (MODY) ............................................................. 35
DIDMOAD Syndrome (Wolfram Syndrome) .................................................................. 36
Mitochondrial Diabetes ................................................................................................... 36
Neonatal Diabetes ........................................................................................................... 36
Cystic Fibrosis and Diabetes ........................................................................................... 37
Drug Induced Diabetes.................................................................................................... 37
Stress Hyperglycaemia .................................................................................................... 37
The Evidence .................................................................................................................. 38
Recommendations and Principles .................................................................................... 38
Reference List ................................................................................................................. 39
Chapter 2: Phases of Diabetes ...................................................................................... 41
Preclinical Diabetes......................................................................................................... 41
Risks of progression to diabetes................................................................................... 41
Presentation of Type 1 Diabetes ...................................................................................... 42
Non-emergency presentations...................................................................................... 42
Emergency presentations............................................................................................. 42
Diagnostic difficulties leading to late diagnosis........................................................... 43
Differentiating between type 1 and type 2 diabetes at diagnosis................................... 43
Partial Remission or Honeymoon Phase .......................................................................... 43
Chronic Phase of Lifelong Dependence on Insulin .......................................................... 43
Transplantation........................................................................................................... 44
The Evidence .................................................................................................................. 44
Reference List ................................................................................................................. 45
Chapter 3: Medical Management................................................................................. 46
Aims of Diabetes Management........................................................................................ 46
Hospital versus Ambulatory Stabilisation ........................................................................ 46
Foundations of Diabetes Management............................................................................. 47
Diabetes Education.......................................................................................................... 47
Insulin Replacement Therapy .......................................................................................... 48
Immunisation .................................................................................................................. 48
Outreach Services ........................................................................................................... 49
Transition to Adult Services ............................................................................................ 49
Cost Issues ...................................................................................................................... 49
Table of Contents
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The Evidence .................................................................................................................. 49
Reference List ................................................................................................................. 51
Chapter 4: Insulin Preparations and Storage ............................................................. 53
Insulin Action ................................................................................................................. 53
Types of Insulin .............................................................................................................. 53
Rapid-acting insulin .................................................................................................... 54
Short-acting insulin ..................................................................................................... 55
Intermediate-acting insulin.......................................................................................... 55
Long-acting insulins .................................................................................................... 55
Basal insulin analogues............................................................................................... 55
Premixed insulin preparations..................................................................................... 56
Local Reactions to Insulin ............................................................................................... 56
Mixing Insulins ............................................................................................................... 56
Insulin Concentrations..................................................................................................... 57
Storage Conditions .......................................................................................................... 57
Adjunct Therapy with Oral Antidiabetic Drugs ............................................................... 57
Cost Issues ...................................................................................................................... 59
The Evidence .................................................................................................................. 59
Reference List ................................................................................................................. 60
Chapter 5: Insulin Regimens and Delivery ................................................................ 62
Insulin Regimens............................................................................................................. 62
Use of Short-Acting Insulin............................................................................................. 63
Use of Intermediate and Long-Acting Insulins................................................................. 64
Regimens using Pre-mixed Insulins................................................................................. 64
Number of Injections per Day ......................................................................................... 64
Total Daily Insulin Dosage and Distribution.................................................................... 65
Insulin Administration..................................................................................................... 65
Insulin absorption ....................................................................................................... 65
Insulin Delivery Devices ................................................................................................. 67
Insulin syringes and pens ............................................................................................ 67
Automatic injection devices ......................................................................................... 68
Jet injection devices..................................................................................................... 68
Indwelling cannulas .................................................................................................... 68
Insulin pumps (CSII) ................................................................................................... 68
Practical Aspects of Insulin Administration..................................................................... 68
Insulin Adjustment .......................................................................................................... 69
Adjusting usual doses of insulin based on blood glucose patterns over several days or
longer.......................................................................................................................... 69
Pro-active day to day adjustments to insulin based on activity and food intake............ 70
Adjustments to correct the current BG level when it is outside the desired range ......... 70
Insulin pump adjustments ............................................................................................ 70
Cost Issues ...................................................................................................................... 71
The Evidence .................................................................................................................. 71
Reference List ................................................................................................................. 72
Chapter 6: Glycaemic Control ..................................................................................... 75
Intensive Diabetes Management ...................................................................................... 75
Risks and Side Effects of Intensive Diabetes Management .............................................. 75
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Indicators of Poor Glycaemic Control ............................................................................. 75
Glycaemic Goals ............................................................................................................. 76
Parameters of Glycaemic Control .................................................................................... 77
Blood Glucose Monitoring .............................................................................................. 77
Timing of blood glucose testing ................................................................................... 77
Techniques for blood glucose testing ........................................................................... 78
Devices for blood glucose testing ................................................................................ 78
Record keeping and review of records ......................................................................... 79
HbA1C ............................................................................................................................. 80
Fructosamine................................................................................................................... 81
Urine Testing for Glucose ............................................................................................... 81
Testing for Ketones ......................................................................................................... 81
Blood ketones .............................................................................................................. 81
Urine ketones .............................................................................................................. 82
The Evidence .................................................................................................................. 82
Reference List ................................................................................................................. 84
Chapter 7: Nutrition ....................................................................................................... 86
Nutrition Therapy............................................................................................................ 86
Nutritional Assessment.................................................................................................... 86
Nutrition Review............................................................................................................. 86
Dietary Recommendations .............................................................................................. 87
Energy Intake.................................................................................................................. 87
Dietary Carbohydrate ...................................................................................................... 88
Glycaemic Index (GI)...................................................................................................... 88
Sugars ............................................................................................................................. 89
Artificially sweetened products.................................................................................... 89
Fibre ............................................................................................................................... 90
Dietary Fat Intake............................................................................................................ 90
Protein ............................................................................................................................ 91
Variations in Advised Meal Patterns and Insulin Regimens ............................................. 91
Age-group Specific Advice ............................................................................................. 92
Infants ......................................................................................................................... 92
Toddlers ...................................................................................................................... 92
Primary school-aged children ..................................................................................... 92
Adolescents ................................................................................................................. 92
The Evidence .................................................................................................................. 93
Reference List ................................................................................................................. 96
Chapter 8: Physical Activity ......................................................................................... 98
Need for Physical Activity and General Recommendations ............................................. 98
Short-Term Effects.......................................................................................................... 98
Long-term Effects ........................................................................................................... 99
The Evidence .................................................................................................................. 99
Recommendations and Principles .................................................................................. 100
Reference List ............................................................................................................... 100
Chapter 9: Diabetic Ketoacidosis .............................................................................. 101
Definition and Aetiology............................................................................................... 101
Epidemiology................................................................................................................ 102
Management ................................................................................................................. 103
Table of Contents
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Steps in the Assessment and Management of Diabetic Ketoacidosis .............................. 103
Investigation ................................................................................................................. 105
Monitoring .................................................................................................................... 106
Rehydration................................................................................................................... 106
Sodium Replacement..................................................................................................... 107
Potassium Replacement................................................................................................. 107
Bicarbonate Replacement .............................................................................................. 108
Insulin........................................................................................................................... 108
Management of Cerebral Oedema ................................................................................. 109
Management of the Recovery Phase .............................................................................. 110
Oral fluids ................................................................................................................. 110
Covering snacks and meals on intravenous insulin infusion....................................... 110
Transition from intravenous to subcutaneous insulin ................................................. 110
The Evidence ................................................................................................................ 111
Reference List ............................................................................................................... 114
Chapter 10: Surgery and Fasting ............................................................................... 117
Emergency Surgery....................................................................................................... 117
Elective Surgery............................................................................................................ 117
Scheduling of Surgery ................................................................................................... 117
Maintaining Metabolic Control ..................................................................................... 117
Intravenous Fluids......................................................................................................... 118
Management of Short or Minor Procedures Involving Sedation or Anaesthesia ............. 118
Patients on twice or three times daily insulin regimens.............................................. 118
Patients on basal-bolus insulin regimens................................................................... 119
Patients on insulin pumps.......................................................................................... 119
Major Surgery or Surgery where Oral Intake is not Possible for a Prolonged Period...... 120
Insulin Infusion Rates.................................................................................................... 120
The Evidence ................................................................................................................ 120
Reference List ............................................................................................................... 121
Chapter 11: Sick Day Management .......................................................................... 122
Diabetes and Infectious Illnesses ................................................................................... 122
Impact of Illnesses on Diabetes ..................................................................................... 122
Infections Causing Little Effect on Blood Glucose Levels ............................................. 122
Infections Causing Low Blood Glucose levels............................................................... 123
Infections Causing High Blood Glucose Levels............................................................. 123
General Principles of Sick Day Management................................................................. 123
Insulin Regimens in Infections associated with Hyperglycaemia and Ketosis ................ 125
Management at home ................................................................................................ 125
Management in hospital ............................................................................................ 126
Insulin Regimens in Infections Associated with Persistent Hypoglycaemia ................... 127
Management at home ................................................................................................ 127
Management in hospital ............................................................................................ 127
Glucagon....................................................................................................................... 127
Minidose Glucagon ....................................................................................................... 127
Insulin Pump Sick Day Management............................................................................. 128
The Evidence ................................................................................................................ 129
Reference List ............................................................................................................... 130
Table of Contents
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Chapter 12: Hypoglycaemia ....................................................................................... 131
Definition...................................................................................................................... 131
Symptoms and Signs ..................................................................................................... 131
Grading ......................................................................................................................... 133
Frequency ..................................................................................................................... 133
Nocturnal Hypoglycaemia............................................................................................. 133
Consequences................................................................................................................ 134
Counter-Regulatory Responses to Hypoglycaemia and Hypoglycaemia Unawareness ... 134
Prevention..................................................................................................................... 135
Confirmation................................................................................................................. 135
Treatment...................................................................................................................... 135
Mild to moderate hypoglycaemia............................................................................... 135
Severe hypoglycaemia ............................................................................................... 136
Follow-Up of Treatment of Hypoglycaemia .................................................................. 136
Hypoglycaemia and Physical Activity ........................................................................... 137
Somogyi Phenomenon................................................................................................... 137
Hypoglycaemia in School.............................................................................................. 137
Foods for Management of Hypoglycaemia .................................................................... 138
The Evidence ................................................................................................................ 138
Reference List ............................................................................................................... 139
Chapter 13: Psychosocial Aspects ............................................................................. 142
Impact on Child............................................................................................................. 142
Impact on Family .......................................................................................................... 142
Psychosocial Factors and Metabolic Control ................................................................. 143
Adherence to Therapy ................................................................................................... 144
Risk Factors .................................................................................................................. 145
Treatments and Interventions ........................................................................................ 145
The Evidence ................................................................................................................ 146
Reference List ............................................................................................................... 147
Chapter 14: Diabetes Complications......................................................................... 150
Discussing Complications ............................................................................................. 150
Diabetic Retinopathy..................................................................................................... 150
Prevalence and association studies of retinopathy..................................................... 151
Screening for retinopathy .......................................................................................... 152
Interventions to prevent or delay progression of diabetic retinopathy ........................ 153
Cataracts ....................................................................................................................... 153
Refractive Errors ........................................................................................................... 153
Diabetic Nephropathy ................................................................................................... 154
Screening for nephropathy ........................................................................................ 154
Interventions to prevent or delay progression of diabetic nephropathy ...................... 155
Diabetic Neuropathy ..................................................................................................... 156
Screening for neuropathy .......................................................................................... 156
Interventions to prevent or delay diabetic neuropathy ............................................... 157
Macrovascular Disease.................................................................................................. 157
Hypertension................................................................................................................. 157
Blood pressure assessment in children and adolescents............................................. 157
Method for BP measurement ..................................................................................... 157
Paediatric reference values ....................................................................................... 158
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Ambulatory blood pressure monitoring...................................................................... 159
Paediatric reference values ....................................................................................... 159
Summary of blood pressure measurement methods .................................................... 159
Age of screening for hypertension.............................................................................. 160
Definition of hypertension ......................................................................................... 160
Management of hypertension..................................................................................... 160
Dyslipidaemia ............................................................................................................... 162
Interventions for dyslipidaemia ................................................................................. 162
Hypercoagulablity ......................................................................................................... 163
Cost Issues .................................................................................................................... 163
The Evidence ................................................................................................................ 163
Reference List ............................................................................................................... 165
Chapter 15: Other Complications and Associated Conditions ............................. 169
Lipodystrophy (Lipoatrophy and Lipohypertrophy)....................................................... 169
Necrobiosis Lipoidica Diabeticorum ............................................................................. 169
Limited Joint Mobility .................................................................................................. 169
Osteopenia .................................................................................................................... 169
Impaired Growth and Development............................................................................... 170
Associated Autoimmune Conditions.............................................................................. 170
Hypothyroidism ......................................................................................................... 170
Hyperthyroidism........................................................................................................ 170
Coeliac disease ......................................................................................................... 171
Vitiligo ...................................................................................................................... 172
Oedema..................................................................................................................... 172
Primary adrenal insufficiency (Addison's disease)..................................................... 172
The Evidence ................................................................................................................ 172
Reference List ............................................................................................................... 173
Chapter 16: Foot Care.................................................................................................. 176
Deformity...................................................................................................................... 176
Plantar Callus................................................................................................................ 177
High Plantar Pressure .................................................................................................... 177
Soft Tissue Changes ...................................................................................................... 177
Limited Joint Mobility .................................................................................................. 178
The Evidence ................................................................................................................ 178
Reference List ............................................................................................................... 179
Chapter 17: Dental Health .......................................................................................... 180
Dental Caries ................................................................................................................ 180
Periodontal Disease....................................................................................................... 180
Prevention and Treatment of Dental Caries and Gingivitis............................................. 181
The Evidence ................................................................................................................ 182
Reference List ............................................................................................................... 182
Chapter 18: Adolescent Health .................................................................................. 184
Introduction................................................................................................................... 184
An Approach to the Assessment of Adolescents ............................................................ 184
Transition to Adult Care................................................................................................ 184
Table of Contents
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Career Options .............................................................................................................. 186
Driving.......................................................................................................................... 186
Risk Taking Behaviour.................................................................................................. 187
Smoking .................................................................................................................... 187
Alcohol...................................................................................................................... 188
Drugs ........................................................................................................................ 189
Sexuality ....................................................................................................................... 189
Impotence.................................................................................................................. 189
Contraceptives .......................................................................................................... 190
Oral contraceptive pill (OCP) ................................................................................... 190
Intrauterine devices (IUDs) ....................................................................................... 190
Barrier methods (condom, diaphragm)...................................................................... 190
Progestogen depot/implant ........................................................................................ 190
Diabetes and Pregnancy ................................................................................................ 191
Eating Disorders............................................................................................................ 191
The Evidence ................................................................................................................ 192
Reference List ............................................................................................................... 193
Chapter 19: School ....................................................................................................... 196
General Considerations in the Development of the Care Plan ........................................ 197
Issues to be Considered in the Individual Care Plan....................................................... 197
Detentions..................................................................................................................... 199
Travel to and from School by Bus ................................................................................. 199
Emergencies at School .................................................................................................. 199
School Examinations..................................................................................................... 199
High School Examinations ............................................................................................ 199
School Camps ............................................................................................................... 200
Short-term Effects of Fluctuations in Glycaemia on Cognitive Function........................ 200
Long-term Effects of Fluctuations in Glycaemia on Cognitive Function ........................ 200
The Evidence ................................................................................................................ 201
Reference List ............................................................................................................... 202
Chapter 20: Diabetes Camps ...................................................................................... 203
Background................................................................................................................... 203
The Need for Diabetes Camps in Australia .................................................................... 203
Benefits......................................................................................................................... 203
Goals............................................................................................................................. 204
Other Benefits ............................................................................................................... 204
Prerequisites.................................................................................................................. 204
Medical Management.................................................................................................... 205
Conclusion .................................................................................................................... 205
Information on diabetes camps ...................................................................................... 205
Reference List ............................................................................................................... 206
Chapter 21: Travelling and Holidays ........................................................................ 207
Preparation.................................................................................................................... 207
Supplies ........................................................................................................................ 207
Management of Diabetes on Long Flights ..................................................................... 208
The Evidence ................................................................................................................ 208
Table of Contents
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Reference List ............................................................................................................... 209
Chapter 22: Complementary and Alternative Medicine ........................................ 210
Complementary and Alternative Medicine use in Diabetes ............................................ 210
Clinicians and Complementary and Alternative Medicine ............................................. 210
Management of a Patient using Complementary and Alternative Medicine.................... 211
The Evidence ................................................................................................................ 212
Reference List ............................................................................................................... 213
Resources ....................................................................................................................... 214
Diabetes Australia (DA) ................................................................................................ 214
Contact Details for Diabetes Australia States & Territories............................................ 214
Juvenile Diabetes Research Foundation (JDRF) ............................................................ 214
Health Care Card........................................................................................................... 214
Carer Allowance (CA)................................................................................................... 215
International Diabetes Federation (IDF) School Information Pack ................................. 215
Other Resources ............................................................................................................ 215
Appendix 1: Guidelines Writing Committee Members and Contributors.......... 216
Writing committee members ......................................................................................... 216
Contributors .................................................................................................................. 217
Appendix 2: Evidence Tables .................................................................................... 219
Chapter 1: Definition, Epidemiology and Classification ................................................ 219
Chapter 2: Phases of Diabetes ....................................................................................... 220
Chapter 3: Medical Management................................................................................... 222
Chapter 4: Insulin Preparations and Storage .................................................................. 226
Chapter 5: Insulin Regimens and delivery ..................................................................... 230
Chapter 6: Glycaemic Control ....................................................................................... 235
Chapter 7: Nutrition ...................................................................................................... 241
Chapter 8: Physical Activity.......................................................................................... 247
Chapter 9: Diabetic Ketoacidosis................................................................................... 248
Chapter 10: Surgery and Fasting.................................................................................... 263
Chapter 11: Sick Day Management ............................................................................... 264
Chapter 12: Hypoglycaemia .......................................................................................... 265
Chapter 13: Psychosocial Aspects ................................................................................. 272
Chapter 14: Diabetes Complications.............................................................................. 280
Chapter 15: Other Complications and Associated Conditions ........................................ 283
Chapter 16: Foot Care ................................................................................................... 285
Chapter 17: Dental Health ............................................................................................. 287
Chapter 18: Adolescent Health Issues............................................................................ 289
Chapter 19: School........................................................................................................ 299
Chapter 20: Diabetes Camps ......................................................................................... 302
Chapter 21: Travelling and Holidays ............................................................................. 302
Chapter 22: Complementary and Alternative Medicine ................................................. 303
Table of Contents
x
Tables
Table I: NHMRC Levels of Evidence.................................................................................... 5
Table II: Recommendation Codes ......................................................................................... 6
Table 1.1: Aetiological Classification of Disorders of Glycaemia........................................ 29
Table 1.2: Other Specific Types of Diabetes........................................................................ 30
Table 1.3: WHO Criteria Values for Diagnosis of Diabetes Mellitus and Other Categories of
Hyperglycaemia .......................................................................................................... 31
Table 4.1: Insulins Currently in Use in Australia ................................................................. 54
Table 5.1: Mean Cutis/Subcutis Thickness .......................................................................... 66
Table 7.1: The Dietary Guidelines for Children and Adolescents in Australia...................... 87
Table 7.2: The Glycaemic Index of Some Foods (Glucose = 100) ....................................... 89
Table 7.3: Summary of the Australian Dietary Guidelines for Dietary Fat Intake during
Childhood ................................................................................................................... 90
Table 10.1: Maintenance Fluid Volume for Different Age Groups .................................... 118
Table 11.1: Emergency Kit For Sick Day Management at Home....................................... 124
Table 11.2: Indicators for Patient to be Transferred to Hospital ......................................... 125
Table 11.3: Sick Day Foods and Fluids ............................................................................. 125
Table 11.4: How to Calculate the Amount of Extra Insulin on Sick Day............................ 126
Table 11.5: Recommended Dose for Mini-dose Glucagon................................................. 127
Table 11.6: Management of Sick Days with Insulin Pump................................................. 128
Table 12.1: Symptoms of Hypoglycaemia in Diabetic Children and Recommendations for its
Treatment.................................................................................................................. 132
Table 14.1: Blood Pressure Ranges for Height Centiles..................................................... 161
Figures
Figure 1.1: Annual Incidence Rates for Type 1 Diabetes (0-14 years age group) Comparing
Different Countries in the World ................................................................................. 27
Figure 4.1: Schematic Action Profiles of Insulin Preparations ............................................. 58
Figure 5.1: Recommended Injection Sites ........................................................................... 66
Figure 7.1: Body Mass Index-for-age Percentiles: Girls, 2-20 Years.................................... 94
Figure 7.2: Body Mass Index-for-age Percentiles: Boys, 2-20 Years ................................... 95
Figure 12.1: Glucagon Kit for Treatment of Hypoglycaemia ............................................. 136
Table of Contents
1
Introduction
Background
The development of the Australian Clinical Practice Guidelines for the Management of Type
1 Diabetes in Children and Adolescents arose out of a recommendation by the National
Diabetes Strategy Group to update the APEG Handbook on Childhood and Adolescent
Diabetes published in 1996. In updating the guidelines, the decision was made to take an
evidence-based approach in order to improve the usefulness of the guidelines for practising
clinicians. The project was funded by the Australian Government Department of Health and
Ageing and carried out by the Australasian Paediatric Endocrine Group in collaboration with
Diabetes Australia and the Juvenile Diabetes Research Foundation. Consumer input was
obtained from the latter two organisations and by nationwide public consultation.
The guidelines development process was coordinated by a national multidisciplinary
writing committee, which met to determine the scope of the work and resolved that the new
guidelines would be aimed at the practising health care professional involved in all aspects of
the care of children and adolescents with type 1 diabetes. It was considered important that the
guidelines were to retain the user-friendly format of the APEG handbook. The guidelines
were developed in accordance with the NHMRC handbook series on preparing clinical
practice guidelines.(1-7)
Rationale for the Guidelines
Type 1 diabetes is the one of the most common chronic diseases of childhood and
adolescence. It affects approximately 10,000 children and adolescents in Australia and its
incidence is rising 2-4% per year. The disease impacts heavily on their lifestyle and that of
their families. Lifelong insulin replacement and monitoring of blood glucose levels are
needed. Children and adolescents with type 1 diabetes are liable to acute, subacute and
chronic complications of diabetes. The development and progression of the chronic
microvascular complications of diabetes are influenced by diabetes control. The transition
process from paediatric to adult services has been highlighted as an area of need. People with
type 1 diabetes are also at greater risk of developing cardiovascular disease. These risks can
be decreased by control of high blood pressure and lipid disorders. Regular review of
diabetes control and of the risk factors for the development of microvascular and
macrovascular complications of diabetes need to form part of the long-term management of
type 1 diabetes. The economic burden of diabetes is high for the individual, the family, the
health care sector and society as a whole. In addition there is a high personal and family
burden in growing up and living with type 1 diabetes.
Scope of the Guidelines
The guidelines address the diagnosis and all relevant aspects relating to the clinical
management of type 1 diabetes in children of all ages, including adolescents up to the point
of transition to adult care.
Areas beyond the remit of the guidelines
The guidelines do not address:
• The management of type 1 diabetes in adults.
• The management of gestational diabetes.
• The management of type 2 diabetes.
Introduction
2
Target Audience
The guidelines are aimed at all health care professionals involved in the care of children and
adolescents with type 1 diabetes.
Guidelines Development Process
Guidelines writing committee
A multidisciplinary writing committee was convened consisting of clinicians, diabetes
educators, consumers, parents, and experts in guideline development. The members of the
Writing Committee and other contributors are listed in Appendix 1.
Review of existing guidelines
Other guidelines, position papers and technical reports regarding the management of type 1
diabetes in children and adolescents were sought from the World Health Organization
(WHO), International Diabetes Federation (IDF), American Diabetes Association (ADA),
National Health and Medical Research Council (NHMRC), Australian Paediatric Endocrine
Group (APEG) and International Society for Pediatric and Adolescent Diabetes (ISPAD). In
addition, the Writing Group was privileged to have access to the UK National Health
Services (NHS) National Institute of Clinical Excellence (NICE) guideline on type 1
diabetes: Diagnosis and Management of type 1 diabetes in children and young people to be
released in 2004, and the findings of the Consensus Statement on Diabetic Ketoacidosis by
the Lawson Wilkins Pediatric Endocrine Society (USA) and the European Society for
Pediatric Endocrinology (ESPE), produced in September, 2003.
The above sources were considered for their usefulness in updating the 1996 APEG
Handbook. The NICE guidelines and the Consensus Statement on Diabetic Ketoacidosis
(DKA), in particular, were found to be evidence-based documents which could be adapted to
inform the update of the 1996 APEG guidelines.
Formulation of Clinical Questions
The writing committee formulated clinical questions which needed to be addressed by the
updated guidelines. Questions were formulated to cover areas of controversy or of particular
concern within the Australian health care context. These questions are listed in Appendix 2.
Locating the Evidence
The relevant literature was systematically searched with the aim of identifying the clinical,
epidemiological, psychosocial, research and diagnostic data relevant to type 1 diabetes in
children and adolescents. Electronic databases (Medline, Embase, the Cochrane Database of
Systematic Reviews and Central Register of Controlled Trials, and, where relevant to the
topic, PsychINFO and CINAHL) were searched from inception to August 31, 2003. Search
strategies were devised to address the clinical questions and incorporated key words, MeSH
terms (Medical Index Subject Headings) and free text terms. All searches were restricted to
English language and Human studies. The only animal study cited was a classic study on CSF
pH changes in diabetic ketoacidosis in dogs which was published in the Journal of Pediatrics
in 1980 (Bureau MA, Begin R, Berthiaume Y, Shapcott D, Khoury K, Gagnon N: Cerebral
hypoxia from bicarbonate infusion in diabetic acidosis. Journal of Pediatrics 96:968-973,
1980). Studies available only as abstracts were excluded from the main analysis. No age limit
was used in the searches (ie all paediatric and adult literature was considered). In considering
Introduction
3
the search yield, the primary focus was on childhood studies. However, the adult literature
was included when considered relevant to childhood and adolescent practice. As it was
anticipated that for many important areas of type 1 diabetes management and care there
would be a paucity of high quality evidence, studies of all types were included. Additional
references were identified from the reference lists of relevant articles and by a ‘call for
information’ from colleagues and experts involved in the writing process of the guidelines.
Evidence tables are listed in Appendix 2.
Four additional references were added to the evidence tables as a result of the public
consultation (Evidence Tables: Chapter 3, Srinivasan et al. 2004; Chapter 4, Sarnblad et al.
2003; Chapter 5, Diglas et al. 1999; Chapter 12, Schoenle et al. 2002). Additional references,
provided by expert reviewers during the public consultation phase, not included in the
evidence tables, but relevant to the background information of the document, were included
after consideration by the writing committee (even if published after the 30th August 2003).
Levels of Evidence and Critical Appraisal
These guidelines searched for evidence for the following issues in detail:
Chapter 1: Definition, Epidemiology and Classification
Prevalence/incidence of type 1 diabetes in children in Australia/worldwide.
• Chapter 2: Phases of Diabetes
Intervention trials to delay or prevent the onset of type 1 diabetes.
• Chapter 3: Medical Management
Benefits of ambulatory care versus hospital in-patient care of patient with newly
diagnosed type 1 diabetes.
Differences in glycaemic control between urban and rural children and adolescents
with type 1 diabetes in the Australian health care system.
The effect of educational interventions on metabolic and psychological outcomes in
children and adolescents with type 1 diabetes.
• Chapter 4: Insulin Preparations and Storage
Benefits of animal insulin over human insulin use in children and adolescents with
type 1 diabetes.
Treatment of children with type 1 diabetes with insulin glargine.
Metformin as an adjunct therapy to insulin in the treatment of children and
• Chapter 5: Insulin Regimens and delivery
Relationship of number of daily insulin injections with glycaemic control.
The length of needle for the injection for insulin therapy in the treatment of children
with type 1 diabetes.
Children and adolescents with type 1 diabetes and management with insulin pump
therapy.
• Chapter 6: Glycaemic Control
Benefits of near patient testing of HbA1c at outpatient visits.
Benefits of improved glycaemic control on development of microvascular and
macrovascular complications.
• Chapter 7: Nutrition
Low glycaemic index diets in the management of type 1 diabetes in children and
adolescents.
Adjusting insulin dose for carbohydrate quantity in the management of type 1 diabetes
in children and adolescents.
•
Introduction
4
•
•
•
•
•
•
•
•
•
•
•
Effect of moderate use of sugars on glycaemic control in children and adolescents
with type 1 diabetes.
Chapter 8: Physical Activity
Longterm effects of physical activity in children and adolescents with type 1 diabetes.
Chapter 9: Diabetic Ketoacidosis
Aetiology, epidemiology, risk factors, cerebral oedema and management of diabetic
ketoacidosis.
Chapter 10: Surgery and Fasting
Management of surgery and fasting in children and adolescents with diabetes.
Chapter 11: Sick Day Management
Insulin adjustment during “sick days” /intercurrent illnesses in children and
Management of severe hypoglycaemia with intravenous glucose or
intramuscular/intravenous glucagon.
Chapter 12: Hypoglycaemia
Effect of intensive diabetes management on the incidence of hypoglycaemia.
Management of severe hypoglycaemia with intravenous glucose or
intramuscular/intravenous glucagon.
Effects of hypoglycaemia on cognitive function in children and adolescents with type
1 diabetes.
Chapter 13: Psychosocial Aspects
The incidence and risk factors for non-adherence with treatment regimens in children
and adolescents with type 1 diabetes.
The effect of psychosocial interventions on metabolic and psychological outcomes in
Chapter 14: Diabetes Complications
Effect of intensive diabetes management on microvascular and macrovascular
complications in adolescents.
How frequently should children and adolescents with type 1 diabetes be screened for
microvascular (retinopathy, nephropathy, neuropathy) complications?
macrovascular complications?
Chapter 15: Other Complications and Associated Conditions
thyroid disease?
How frequently should children and adolescents with Type 1 diabetes be screened for
coeliac disease?
Effect of a gluten free diet (GFD) in asymptomatic patients with type 1 diabetes found
to have coeliac disease on routine screening.
Chapter 16: Foot Care
The effect of type 1 diabetes on joint mobility in the feet of young people.
The management of high plantar pressure and callus in adolescents with type 1
diabetes.
foot complications?
Chapter 17: Dental Health
How frequently should children and adolescents with type 1 diabetes have a dental
review?
The effect of type 1 diabetes on dental health in children and adolescents.
Chapter 18: Adolescent Health
Introduction
5
•
•
•
•
Glycaemic control in adolescents compared with adults.
Current transition processes and outcomes for adolescents with type 1 diabetes
moving to the adult care system
The effect of type 1 diabetes on driving performance.
Eating disorders in type 1 diabetes.
Chapter 19: School
Effects of type 1 diabetes on cognitive function in children and adolescents.
Chapter 20: Diabetes Camps
Benefits on glycaemic control of diabetes camps in children with type 1 diabetes.
Chapter 21: Travelling and Holidays
Insulin regimens during travel when crossing time zones.
Chapter 22: Complementary and Alternative Medicine
Do complementary and alternative medicine therapies cure or improve diabetes in
children?
Identified studies were assigned a level of evidence according to the NHMRC Hierarchy of
Evidence (NHMRC, 2001) (Table I) and are included in the Evidence tables. Those studies
which were used to formulate recommendations (and thus provided the evidence-base for
those recommendations) were critically appraised for their methodological quality. Other
recommendations and principles of clinical practice in the guidelines have been based on
Technical Reports or when no level I-IV information existed, on Consensus Statements based
on expert opinion. Apart from outlining recommendations and principles of clinical practice
the guidelines provide a wealth of highly referenced information for practicing clinicians and
health care professionals.
Study quality was assessed on a number of parameters such as the quality of the study
methodology reporting, methods of randomisation and allocation concealment (for
Randomised Control Trials (RCT’s)), blinding of patients or outcomes assessors, attempts
made to minimise bias, sample sizes and the ability of the study to measure ‘true effect’. The
applicability of results outside the study sample was also examined as were the
appropriateness of the statistical methods used to describe and evaluate the study data.
As the NHMRC levels of evidence are designed for application specifically to intervention
studies, the population-based studies, cohort studies and case-control studies which were
identified by the literature search are allocated a relatively low level of evidence. The highest
level of evidence that can be allocated to these studies based upon NHMRC criteria is Level
IV. This does not reflect the high level and quality of many of the population-based studies
referenced in the guidelines and used to base recommendation upon.
Table I: NHMRC Levels of Evidence
I
II
III-1
Level I
Level II
Level III-1
III-2
Level III-2
III-3
Level III-3
IV
Level IV
Evidence from a systemic review of all relevant RCT’s
Evidence from at least one properly-designed RCT
Evidence from well-designed pseudo-randomised controlled
trials (alternate allocation or some other method).
Evidence from comparative studies with concurrent controls and
allocation, non-randomised (cohort studies), case-control
studies, or interrupted time series with a control group
Evidence from comparative studies with historical control, two
or more single-arm studies, or interrupted time series without a
parallel control group
Evidence from case series, either post-test or pre-test and posttest
Introduction
6
Economic Considerations
A broad literature search was designed to find all economic studies relating to children and
adolescents with type 1 diabetes. All studies addressing resource utilisation as well as studies
comparing the costs of different alternatives (economic evaluations) were considered if they
were generalisable to the Australian health care system. These were incorporated into the
relevant chapters within the guidelines. It was agreed that a new economic evaluation would
only be relevant if guidelines recommendations had major resource implications or
represented a change in policy.
Guidelines Review Date
The recommendations in the guidelines incorporate the most recent published evidence,
position papers, technical reports and consensus statements as of August 31, 2003. In view of
the anticipated advances in diabetes research and management it is recommended that the
guidelines should be reviewed after five years in 2008.
Structure of the Guidelines
In writing the guidelines, the writing committee aimed to retain the user-friendly format of
the original 1996 APEG guidelines. For this reason it was decided to incorporate the
available evidence and recommendations for care within the context of the overall discussion
of the topic. At the end of each chapter the important evidence is summarised according to
levels of evidence, and recommendations arising from the available evidence are made (with
the corresponding level of evidence indicated using the NHMRC roman numeral system).
Where no studies could be located recommendations were made based on state, national and
international consensus statements, WHO technical reports, NICE technology appraisals and
other relevant technical reports. Where this occurs it is clearly indicated in the text by the use
of identifying codes as listed in Table II below:
Table II: Recommendation Codes
C
Consensus
T
WHO technical reports
Consensus statement endorsed by professional organisations
Consensus statement from Government Health Departments
Technical reports produced by expert panels convened by WHO
Evidence tables summarising the studies which constituted the evidence-base for the
recommendations can be found in Appendix 2.
Overview of the Guidelines
The guidelines are comprehensively referenced and incorporate up-to-date evidence-based
and expert consensus management recommendations. The initial chapters contain the most
recent information on diagnosis, classification and epidemiology of type 1 diabetes, the
phases of diabetes, the options for the initial management of diabetes, the currently available
insulin preparations and regimens, and, the methods of monitoring metabolic control. A
detailed description is provided of the international consensus management guidelines of
diabetic ketoacidosis as well as the management of the child with diabetes undergoing minor
and major surgery. The guidelines offer practical advice on the problems of hypoglycaemia,
sick day management, travelling and holidays. The psychosocial issues of diabetes are
detailed as well as school and adolescent health issues. Comprehensive guidance is provided
Introduction
7
on the screening for and the management of the chronic complications of diabetes. Other
complications including thyroid disease, coeliac disease are also addressed as well as foot
care and dental health. The challenges of transition from paediatric to adult care are reviewed
and guidance how best to manage this difficult stage is offered.
Consultation and Peer-review Process
The consultation and peer-review process included a nationally advertised call for public
comment, invitations for critical review by members of the Australasian Paediatric Endocrine
Group, International Society for Pediatric and Adolescent Diabetes, International Diabetes
Federation Consultative Section on Childhood and Adolescent Diabetes, Diabetes Australia,
Australian Diabetes Society, Royal Australasian College of Physicians, Royal Australian
College of General Practitioners, Dietitians Association of Australia, Australian Diabetes
Educators Association and the Juvenile Diabetes Research Foundation. The comment were
collated, de-identified, formally considered and addressed by the Guideline Writing Group.
Dissemination
The full text of the guidelines will be freely available as a pdf file on the NHMRC and APEG
websites.
Legal Considerations
The following statement applies to the guidelines: ‘Every attempt has been made to locate the
most recent evidence. Judgement is necessary when applying evidence in a clinical setting. It
is important to note that weak evidence does not necessarily mean that a practice is
unadvisable, but may reflect the insufficiency of evidence or the limitations of scientific
investigation. The guidelines are intended to act as a guide to practice. The ultimate decision
of what to do rests with the practitioner and the consumer and depends on individual
circumstances and belief (NHMRC 1999)’.
Reference List
1.
2.
3.
4.
5.
6.
7.
National Health and Medical Research Council: How to review the evidence: systematic identification and review of the scientific
literature. AusInfo, 1999
National Health and Medical Research Council: A guide to the development, implementation and evaluation of clinical practice
guidelines. AusInfo, 1999
National Health and Medical Research Council: How to present the evidence for consumers: preparation of consumer publications.
AusInfo, 1999
National Health and Medical Research Council: How to put the evidence into practice: implementation and dissemination strategies.
AusInfo, 2000
National Health and Medical Research Council: How to use the evidence: assessment and application of scientific evidence. AusInfo,
2000
National Health and Medical Research Council: How to compare the costs and benefits: evaluation of the economic evidence. AusInfo,
2001
National Health and Medical Research Council: Using socioeconomic evidence in clinical practice guidelines. AusInfo, 2002
Introduction
8
List of Abbreviations
ADA
APEG
APS
BMI
BP
CBGM
CSII
DCCT
DIDMOAD
DKA
DPT
EDIC
EMA
ENDIT
HDL
HLA
HNF
ICA
IDDM
IDF
IFG
IGT
IVGTT
JDRF
LDL
MODY
MRDM
NATA
NICE
NIDDM
OCP
OGTT
SDS
WHO
American Diabetes Association
Australasian Paediatric Endocrine Group
Autoimmune Polyglandular Syndrome
Body Mass Index
Blood pressure
Continuous Blood Glucose Monitoring
Continuous Subcutaneous Insulin Infusion
Diabetes Control and Complications Trial
Diabetes Insipidus Diabetes Mellitus Optic Atrophy Deafness
Diabetic Ketoacidosis
Diabetes Prevention Trial
Epidemiology of Diabetes Interventions and Complications
Antiendomysial Antibodies
European Nicotinamide Diabetes Intervention Trial
High Density Lipoprotein
Human Leucocyte Antigen
Hepatic Nuclear Factor
Islet Cell Antigen
Insulin Dependent Diabetes Mellitus
International Diabetes Federation
Impaired Fasting Glycaemia
Impaired Glucose Tolerance
Intravenous Glucose Tolerance Test
Juvenile Diabetes Research Foundation
Low Density Lipoprotein
Maturity Onset Diabetes in the Young
Malnutrition Related Diabetes Mellitus
National Association of Testing Authorities
National Institute for Clinical Excellence
Non-insulin Dependent Diabetes Mellitus
Oral Contraceptive Pill
Oral Glucose Tolerance Test
tandard Deviation Score
World Health Organization
Glossary
Acanthosis nigricans
Genu valgum
Genu varum
Hypocapnia
Hypo(hyper)kalaemia
dark wart-like patches on neck and in skin folds
knock knee
bow-leg
low blood CO2 level
Low(high) blood potassium
List of Abbreviations
9
Acknowledgements
The Writing Group wishes to acknowledge the outstanding contributions made by Dr Ann
Maguire, APEG Fellow, to the development of the guidelines and the referencing and
evidence basing the guidelines. The expert secretarial assistance of Ms Jane Haynes is most
gratefully acknowledged. The Writing Group also wishes to acknowledge the critical review
and advice provided by the ASERNIPS GAR experts (Ms Philippa Middleton and Dr
Rebecca Tooher).
Acknowledgements
10
Executive Summary of Recommendations and Principles
1. Definition, Epidemiology and Classification
• The diagnosis of diabetes in children and adolescents should be based on the World
Health Organization criteria (1999).1(T)
• Worldwide the incidence of type 1 diabetes in childhood varies greatly (0.1 - 37.4 per
100,000), with the Australian incidence being 17.8 and increasing by 3.2% per year
since 1990.2-5(IV)
• Diabetes can be diagnosed if the characteristic symptoms and signs are present and the
fasting venous plasma glucose concentration is greater than or equal to 7.0 mmol/L,
and/or the random venous plasma glucose concentration taken at least 2 hours after
eating is greater than or equal to 11.1 mmol/L.1(T)
• The possibility of type 2 diabetes should be considered in children and adolescents with
diabetes who are obese, have a strong family history of type 2 diabetes, come from an
ethnic background at high risk for diabetes, produce little or no ketonuria and show
evidence of insulin resistance (acanthosis nigricans or polycystic ovary
syndrome).1;6(T,C)
• The possibility of other types of diabetes should be considered in children and
adolescents with diabetes who have any of the following: an autosomal dominant
family history of diabetes, have associated conditions such as deafness, optic atrophy or
syndromic features, have marked insulin resistance or require little or no insulin outside
the partial remission phase or have been exposed to drugs known to be toxic to beta
cells or cause insulin resistance.1;7(T,C)
• An oral glucose tolerance test (OGTT) is rarely indicated in making the diagnosis of
type 1 diabetes in childhood and adolescence.1;7(T,C)
• The OGTT may be used in the evaluation of possible glucose intolerance in a child or
adolescent suspected of having the metabolic syndrome eg an obese adolescent with
acanthosis nigricans, a girl with the polycystic ovary syndrome, an obese child with a
family history of type 2 diabetes or an obese child from a high risk ethnic background
for type 2 diabetes.6;8(C,T,)
• Targeted screening for type 2 diabetes (fasting plasma glucose or 2 hour post-prandial
glucose) is recommended at the point of medical contact if high risk factors are present
(obesity, strong family history of type 2 diabetes, high risk ethnic group, acanthosis
nigricans, polycystic ovary syndrome) and every 2 years thereafter.8;9(T,C)
2. Phases of Diabetes
• Health care professionals should be aware that there are no interventions shown to
delay or prevent the onset of type 1 diabetes.10;11(II)
• Neither screening of any population nor intervention in the preclinical phase should
occur outside the context of defined clinical studies.12(C)
• Type 1 diabetes is characterised by a preclinical, clinical, partial remission and chronic
phase.7(C)
• The clinical presentation of diabetes can vary from non-emergency presentations (eg
polydipsia, polyuria, weight loss, enuresis) to severe dehydration, shock and diabetic
ketoacidosis.1;7(T,C)
• Parents and children with type 1 diabetes should be informed that the partial remission
phase of diabetes is transient and does not indicate remission of diabetes.7(C)
11
3. Medical Management
• Every child and adolescent with type 1 diabetes, including those from rural and remote
areas, should have access to optimal medical management.7;13;170(C)
• Health care professionals who look after children must make advocacy for the child one
of their key responsibilities.13(C)
• Older children and adolescents who develop diabetes but are not dehydrated or acidotic
may be considered for management out of hospital if expert diabetes support teams are
available.14-21(I)
• Relative contraindications to ambulatory initiation of insulin therapy include very
young age (under 2 years), ketoacidosis, dehydration (moderate or severe), geographic
isolation, no telephone at home, language or other communication difficulties, profound
grief reaction and significant psychological or psychiatric problems within the
family.7;13(C)
• Children and adolescents with type 1 diabetes should have access to care by a
multidisciplinary team trained in childhood diabetes.7;22-24(C)
• The older child and the family should be recognised as being part of the management
team.(C)
• Diabetes education should be part of the management of type 1 diabetes in children and
adolescents. Educational interventions have beneficial effects on diabetes management
outcomes.25(I)
• Education should be adapted to each individual’s age, maturity, stage of diabetes,
lifestyle and culture.7(C)
• After the initial period of diagnosis and education (when frequent contact may be
required), the child should be regularly reviewed throughout the year. This should be no
less than 3-4 times per year), including one major annual review (paying particular
attention to growth, blood pressure, puberty, associated conditions, nutrition and
complications) with the multidisciplinary team.7;23;24(C)
• Children and adolescents with type 1 diabetes should be immunised according to the
Australian Standard Immunisation Schedule166 unless a contra-indication is present.
Diabetes is not a contra-indication to immunisation.(C)
• In rural and geographically remote areas within the Australian health care system,
children with diabetes may be successfully cared for by a local paediatrician/physician
with training and experience in paediatric diabetes, access to resources, support and
advice from a tertiary centre diabetes team.26;27(IV)
4. Insulin Preparations and Storage
• Health care professionals, parents and children and adolescents with type 1 diabetes
should be informed that insulin is essential for survival. There is no alternative to
treatment with insulin.1(T)
• Children and adolescents with type 1 diabetes should be treated with human insulin as
animal insulin has no advantage over human insulin in terms of metabolic control or
hypoglycaemia.28(I)
• A wide variety of human, analogue and bovine insulins are available in Australia for
use in children and adolescents with type 1 diabetes.13(C)
• Rapid-acting insulin should be injected at the time of a meal and short-acting insulin
should be injected 15-20 minutes before a meal.29;30(C)
• Rapid-acting insulin can be administered post-prandially in prepubertal children with
type 1 diabetes with unpredictable eating habits (eg infants, toddlers and preschool
children).29(C)
12
•
•
•
•
•
•
Insulin glargine is a long-acting basal insulin analogue which has recently been
introduced as a treatment option.31(I)
To avoid confusion and prescribing errors, the use of the terms ‘clear’ to describe rapidacting or short-acting insulin and ‘cloudy’ to describe intermediate- or long-acting
insulin, should be discouraged as the long-acting analogues, glargine and detemir, are
clear solutions.(C)
The action profile of the various insulin preparations is subject to inter- and intraindividual variation. The action profile is also affected by storage conditions and the
manufacturer’s storage instruction should be followed.29(C)
All children should have rapid/short-acting insulin available for sick-day
management.7;29(C)
Families need to ensure that a small supply of spare insulin is always available so that
supply is uninterrupted.7(C)
As there is limited and inconsistent evidence on the use and efficacy of metformin as an
adjunct therapy in type 1 diabetes, it should only be considered as an adjunct for
difficult to control patients with evidence of insulin resistance. Patients should be
warned of and closely monitored for hypoglycaemia during the stabilisation period and
the efficacy monitored.32-34(II)
5. Insulin Regimens and Delivery
35• There is a variable effect of the number of daily injections on metabolic control.
37
•
•
•
•
•
•
•
•
•
(II,IV)
Intensive management (including multiple daily injections or pump therapy, education,
intensive monitoring and psychosocial support) of type 1 diabetes in adolescents
improves metabolic control and reduces the risk of microvascular complications.38;39(II)
Many insulin regimens are used in the treatment of type 1 diabetes in children and
adolescents. Any insulin regimen has to be considered in the wider context of a total
diabetes management package, which must include dietary management, exercise and
physical activity, blood glucose monitoring, initial and ongoing education, regular
medical follow-up and psychological care.7;40(C)
Insulin doses should be tailored for each patient’s individual circumstances and
requirements, taking into account age, weight, stage of puberty, duration of diabetes,
food intake and distribution, exercise patterns, daily routines, results of monitoring and
intercurrent illness.7;13(C)
It is recommended that insulin be injected in the abdomen, buttock or non-exercising
thighs. The upper arm is generally not recommended because of the thin layer of
subcutaneous tissue at this site and the increased risk of intramuscular injection.13;40(C)
There is a significant risk of accidental intramuscular injections (and hence more rapid
absorption) especially in lean individuals. This can be minimised by using a two finger
pinch technique, an injection angle of 45 degrees and 8 mm needles.41(II)
5 or 6 mm needles may be appropriate in lean children or those using pens.29;40(C)
Insulin pumps should be considered as a treatment option.42-44(I)
Insulin pump therapy should be initiated and supervised by a specialised multidisciplinary team trained in pump therapy in children and adolescents with
diabetes.42(C)
Insulin syringes and pen needles need to be disposed of in a safe and hygienic way.
Needles should not be recapped to avoid the risk of needle-stick injury. Approved
sharps containers should be provided and disposed of according to local authority
regulations.40(C)
13
•
Health care professionals should educate and encourage children and their families to
acquire skills in insulin adjustment.40(C)
6. Glycaemic Control
• Diabetes Control should be optimised as much as possible as improved glycaemic
control reduces the risk of development and progression of microvascular and
macrovascular complications in adolescents and adults.38;39;45-48(II)
• Frequent daily blood glucose monitoring as part of a package of care has been shown to
be associated with improved glycaemic control.49(T)
• The frequency of blood glucose monitoring should be adapted to the insulin regimen,
the age of the child and the stability of the diabetes.29(C)
• The use of memory-glucose meters without daily reviewing of glucose levels is not
recommended as patterns of glycaemic changes may not be appreciated by the child or
adolescent and the family, and appropriate changes in insulin dosage may not be
made.40(C)
• HbA1c is the only measure of glycaemic control that has been shown to be associated
with long-term complications of diabetes and best reflects glycaemic levels over the
preceding 2-3 months.49(T)
• The American Diabetes Association recommends measuring the HbA1c at least twice
per year in patients who are meeting treatment goals, and more frequently (quarterly) in
those whose treatment has changed or who are not meeting glycaemic goals.50(C)
• HbA1c results should be available at the time of the clinic visit as this may influence the
outcome of the consultation.51(III-1)
7;29
• In older children and adolescents the target HbA1c should be <7.5%. (T,C)
• Increased efforts to improve glycaemic control are recommended as fewer than 25% of
children and adolescents in NSW had HbA1c levels <7.5%.26;36(IV)
• In younger children, the HbA1c target may be set a little higher because of the dangers
of hypoglycaemia to the developing brain.29(IV)
• HbA1c values need to be interpreted in the context of blood glucose readings and
clinical parameters (eg a child with a low HbA1c may be experiencing asymptomatic
hypoglycaemia).40(C)
• Children whose HbA1c is rising or is persistently elevated should have all aspects of
their diabetes management reassessed.29(C)
• Ketones should be tested for when the blood glucose is above 15 mmol/L and the child
or adolescent is unwell.7(C)
• Ketones should be tested for in the presence of abdominal pains, rapid breathing,
flushed cheeks, high temperature, vomiting, diarrhoea or inappropriate drowsiness even
when the blood glucose is <15 mmol/L.40(C)
7. Nutrition
• Nutrition is a fundamental component in the management of type 1 diabetes in
childhood and adolescence.52;53(C)
• Nutritional management of children and adolescents with type 1 diabetes should be
initiated by an accredited practising dietitian trained in paediatric diabetes.13(C)
• Nutritional reviews should occur 2-4 weeks post-diagnosis and ongoing at least once
per year by a paediatric dietitian experienced in diabetes management.13(C)
• Children and adolescents with diabetes should be encouraged to follow the NHMRC
Dietary Guidelines for Children and Adolescents in Australia which recommend
that:54(C)
Carbohydrate should provide 50-55% of total energy intake.
14
Dietary fat intake should provide between 25 and 40% of total energy intake
depending on the child’s age.
Saturated fat intake should be limited to <10% of total energy intake.
Dietary protein intake should provide 15-20% of total energy intake.
Children and adolescents with diabetes should be educated and encouraged to adjust
their insulin dose depending upon carbohydrate quantity.55;56(II)
Day to day consistency in carbohydrate intake is important for those receiving fixed
doses of insulin.(C)
Dietary advice should include information about low glycaemic index food as this can
help to improve glycaemic control.57;167-169(I)
Moderate use of sucrose in the diabetes diet should be allowed as it does not
significantly influence glycaemic control in type 1 diabetes.58-62(II)
•
•
•
•
8. Physical Activity
• Physical activity should be considered part of diabetes management. Children and
adolescents with type 1 diabetes should be encouraged to participate in a variety of
sport and physical activity and not be limited in their choice of activity.13(C)
• Regular physical activity in children and adolescents with type 1 diabetes should be
encouraged as it can improve aerobic capacity and muscle strength; however the
reported effect of physical activity on glycaemic control (measured by HbA1c) varies.6365
•
•
•
•
•
•
•
(II)
Activities should be approached with caution if they are solo in nature, take place in
water or mid-air, or limit the individual’s ability to recognise and self-treat
hypoglycaemia and a ‘buddy’ is recommended.13(C)
Blood glucose levels need to be measured before, during and after physical
activity.29(C)
Physical activity may necessitate extra carbohydrate intake and insulin reduction.
Experience and blood glucose monitoring help determine the most appropriate
strategies as the requirements vary for each individual.29(C)
All children and adolescents participating in sport should have access to assistance
from a person aware of the management of hypoglycaemia.(C)
A general recommendation is that 15 gm of easily consumed and quickly absorbed
carbohydrate or an extra serving should be taken for every 30 minutes of moderate to
intensive sport or physical activity.(C)
Extra carbohydrate should be consumed if blood glucose level is <7 mmol/L.29;40(C)
Strenuous physical activity should be avoided if blood glucose levels are >15 mmol/L
especially if ketones are present.40(C)
9. Diabetic Ketoacidosis
• The guidelines for the management of diabetic ketoacidosis should take into account
the conclusions of a consensus statement resulting from a workshop that took place in
the United Kingdom in June 2003 involving the European Society for Paediatric
Endocrinology (ESPE), the Lawson Wilkins Pediatric Endocrine Society (LWPES) and
other societies including the Australasian Paediatric Endocrine group (APEG).66(C)
• The most common precipitating factors in the development of diabetic ketoacidosis
include infection, often as a result of inadequate insulin therapy during intercurrent
illness and insulin omission.67-72(IV)
• Diabetic ketoacidosis is the most common cause of death in newly diagnosed type 1
diabetes.68-70;73 (IV)
15
•
The greatest risk of mortality from diabetic ketoacidosis is from cerebral oedema.6870;74;75
(IV)
•
•
•
•
•
•
•
•
Although poorly understood, the risk factors for cerebral oedema in diabetic
ketoacidosis include presentation with new onset type 1 diabetes,75-77 younger age,76-78
elevated serum urea nitrogen and/or severity of dehydration at presentation, severity of
acidosis,74;79 greater hypocapnia at presentation (after adjusting for degree of acidosis),
an attenuated rise in serum sodium during treatment for diabetic ketoacidosis;74;80-82
bicarbonate treatment to correct acidosis has also been associated with cerebral
oedema.74;83(III,IV)
Immediate assessment for diabetic ketoacidosis should consist of clinical history,
assessment and biochemical confirmation (see algorithm in Chapter 9).7(C)
‘Low dose’ intravenous insulin is recommended for the treatment of moderate to severe
diabetic ketoacidosis.66(C)
A specialist/consultant paediatrician with training and expertise in the management of
diabetic ketoacidosis should direct management.66(C)
The child should be cared for in a unit that has experienced nursing staff trained in
monitoring and management of diabetic ketoacidosis, clear written guidelines for
managing diabetic ketoacidosis and access to laboratories that can provide frequent and
accurate measurement of biochemical variables.66(C)
Children with ketosis and hyperglycaemia, but who are not vomiting, may be managed
at home or in an ambulatory care setting (such as an emergency ward).84;85(IV)
Children with signs of severe diabetic ketoacidosis or those who may be at increased
risk for cerebral oedema should be considered for immediate treatment in an intensive
care unit (paediatric if possible) or a children’s ward specialising in diabetes care.(C)
The management of cerebral oedema in diabetic ketoacidosis is a medical emergency
and treatment (fluid restriction, mannitol, neurological assessment) should be initiated
in an intensive care facility as soon as the condition is suspected.77;86(IV)
10. Surgery and Fasting
• Surgery on children with diabetes should only be undertaken in hospitals with
dedicated paediatric facilities for the care of children with diabetes and expert staff
(medical, anaesthetic, surgical and nursing).7;13(C)
• When fasting before an anaesthetic an intravenous glucose infusion should be
commenced to prevent hypoglycaemia.7;13(C)
• Children with type 1 diabetes requiring a surgical procedure should receive insulin,
even if fasting, to avoid ketoacidosis. There may be increased insulin requirements
peri-operatively due to physiological stress and increased counter-regulatory
hormones.87(III-3)
• In children and adolescents with type 1 diabetes the optimal method of maintaining
metabolic control during major surgery or prolonged post-operative fasting is by an
insulin infusion.87(III-3)
11. Sick Day Management
• Families should be informed that intercurrent illnesses can cause high or low blood
glucose levels.7;13;40(C)
• All families should receive education about the management of sick days and have a
sick day kit at home containing rapid-acting or short-acting insulin, glucose test strips,
meters, lancets/finger pricking devices, urine test strips for glucose and ketone
estimation or blood ketone meter and strips, doctor’s/hospital’s phone number, sweet
cordial/fruit juice/lemonade or other soft drinks, low joule (diet drinks) or water,
16
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•
•
•
•
•
•
•
•
glucagon, diabetes manual or emergency guidelines, sick day foods, thermometer,
paracetamol or ibuprofen (sugar-free syrup or tablets).7;13;40(C)
Insulin should never be omitted even if unable to eat.7;13;40(C)
Blood glucose and ketones should be monitored frequently.7;13;40(C)
Any underlying illness should be treated promptly.7;13;40(C)
Extra oral fluids should be encouraged especially if the blood glucose is high or ketones
are present.7;13;40(C)
Additional boluses of short/rapid-acting insulin equal to 10-20 per cent of the total
insulin daily dosage should be given every 2-4 hours if the blood glucose is high and
ketones are present.7;13;40(C)
Patients/carers should seek assistance immediately if, after extra insulin boluses, the
blood glucose remains high, ketones persist, or nausea, vomiting or abdominal pain
develop.7;13;40(C)
Severe hypoglycaemia should be treated with intravenous dextrose (in the hospital
setting).88;89(II)
If venous access is difficult or outside the hospital setting, intramuscular glucagon
should be used to treat severe hypoglycaemia.7;13;40(C)
Under the supervision of a doctor or diabetes educator, small doses of subcutaneous
glucagon may be used to prevent or treat mild hypoglycaemia in an ambulatory
setting.90(IV)
12. Hypoglycaemia
26;36;38;45;91
• Hypoglycaemia is the most frequent acute complication of type 1 diabetes.
(II)
• Hypoglycaemia is the major factor limiting intensified regimens aiming for nearnormoglycaemia.26;36;38;45;91(II)
• Severe hypoglycaemia should be avoided in children, especially in those less than 5 yrs
old.92-98(II, III, IV)
• Blood glucose values should be maintained above 4.0 mmol/L in children and
adolescents with diabetes.7;13;40(C)
• Children and adolescents with diabetes should wear some form of identification or
warning of their diabetes.7;13;40(C)
• All children and adolescents with diabetes should carry glucose tablets or readily
absorbed carbohydrate (preferably in waterproof sealed wrap) on their person and have
glucagon available at home (and in boarding schools where there is a nurse on
staff).7;13;40(C)
• Hypoglycaemia in children is largely preventable; however there is a significant
proportion of severe hypoglycaemic episodes in which no obvious cause can be
determined.13;40(C)
• School teachers and carers at schools should be informed of the symptoms and
appropriate treatment of hypoglycaemia and should have access to advice when
necessary.7;13;40(C)
• In the hospital setting severe hypoglycaemia should be treated with intravenous
dextrose as this is the most rapid way of treating severe hypoglycaemia.88;89(II)
• The recommended dose of intravenous dextrose is 2-5ml/kg of 10% dextrose. 50%
dextrose should not be used because of dangers of tissue necrosis associated with
extravasation.(C)
• Intramuscular or subcutaneous glucagon is an effective way of treating severe
hypoglycaemia in a home-care setting or if intravenous dextrose is not possible.88;89(II)
17
13. Psychosocial Aspects
• Type 1 diabetes in childhood imposes a number of psychological stresses on both the
child and the family.7;13;29;40(C)
• Non-adherence to the diabetes regimen is common in children and adolescents with
type 1 diabetes.72;99-111(IV)
• Non-adherence with treatment regimens is common especially during teenage
years,72;104-106 when an underlying psychiatric disorder is present,99;102;109 when the
parents or child have a low level of education,101;111 when self-care autonomy is
promoted or impeded at an inappropriate time,112 and when there is low level of
cohesion within the family.111(IV)
• Health care professionals should be aware that adolescents may omit or reduce insulin
doses in order to produce glycosuria as a method of weight control.113-115(IV)
• Psychological interventions have been shown to improve HbA1c and psychosocial
outcomes.25;116-118(I)
14. Diabetes Complications
• Type 1 diabetes confers the risk of long-term diabetes microvascular
complications.38;45;48;119(II)
• Families with a child or adolescent with diabetes should be made aware of the potential
long-term complications of diabetes as part of their diabetes education. Adolescents
should be made aware at a rate appropriate to their maturity.7;13(C)
• Families with a child or adolescent with diabetes should be made aware that long-term
good metabolic control reduces the risk of development and progress of
complications.38;45(II)
• Families with a child or adolescent with diabetes should be made aware that other
modifiable risk factors for diabetic microvascular complications include higher blood
pressure, smoking and dyslipidaemia.38;45(II)
• Screening for retinopathy should be performed annually in adolescents after 2 years of
diabetes and after 5 years of diabetes in those who are prepubertal.7;13(C)
• Assessment for retinopathy should be by an observer with special expertise in diabetic
eye disease. If stereoscopic fundal photography is used then biennial assessment may
be appropriate for those with minimal background retinopathy, diabetes duration of less
than 10 years and if the HbA1c is not significantly elevated. If moderately severe
retinopathy is present then more frequent review is necessary.13;120(C)
• Clinical examination of the eyes for cataracts should be performed soon after diagnosis,
especially if there has been slow or prolonged onset of diabetes.7;13(C)
• Screening for microalbuminuria should be performed annually in adolescents after 2
years of diabetes and after 5 years of diabetes in those who are prepubertal. Assessment
should be either by timed overnight urine collections or a spot urinary
albumin/creatinine ratio. If microalbuminuria is found then screening should be more
frequent, and other renal investigations undertaken and specific focus should be placed
on blood pressure measurements.7;13(C)
• In the presence of poor diabetes control, clinical evaluation of peripheral nerve function
should occur annually and should as a minimum include:13(C)
History (especially of numbness, pain, paraesthesia).
Assessment of vibration sensation (by tuning fork or biothesiometer).
Assessment of ankle reflexes.
Assessment of sensation.
• Type 1 diabetes frequently results in accelerated atherosclerosis. Good glycaemic
control can decrease this risk.48;119(II)
18
•
Blood pressure measurements should be recorded at diagnosis and, if normal, annually.
Hypertension should be considered to be present if repeated blood pressure levels are
>95th centile for age, gender and height specific normative data.13(C)
• Screening for lipid disorders should begin within 6-12 months of diagnosis of diabetes,
and if normal should be performed every 5 years in prepubertal children and every
second year in pubertal children).22;121(C)
15. Other Complications and Associated Conditions
• Monitoring of growth and development and the use of growth charts is a very important
part of ongoing care of children and adolescents with type 1 diabetes.7;13(C)
• Screening of thyroid function by Thyroid Stimulating Hormone (TSH) every 2 years is
recommended in asymptomatic individuals without a goitre or in the absence of thyroid
autoantibodies. More frequent assessment is indicated otherwise.7(C)
• Screening for coeliac disease should be carried out around the time of diagnosis and
every 2-3 years thereafter. More frequent assessment is indicated if the clinical situation
suggests the possibility of coeliac disease.7;13;29(C)
• Although the benefits of a gluten-free diet have not been proven in those with type 1
diabetes detected to have coeliac disease on routine screening,122;123 these children
should be referred to a paediatric gastroenterologist and on confirmation of the
diagnosis receive support from a paediatric dietitian with experience in gluten-free
diets.13;40(C)
16. Foot Care
• Health care professionals should be aware that the structural and functional
abnormalities known to predispose adults with diabetes to plantar ulceration are already
present in young people with diabetes.124-126(IV)
• Young people presenting with plantar callus, or detected to have high plantar pressures
or limited joint mobility need to be monitored closely for foot complications.13(C)
• Orthosis, cushioning or both in combination may be used to treat high peak plantar
pressure.127(IV)
17. Dental Health
• Children and adolescents with type 1 diabetes should be informed that dental decay is
increased when glycaemic control is poor.128(IV)
• Health care professionals should be aware that diabetes is a risk factor for periodontal
disease especially when metabolic control is poor or when diabetes duration is long.129132
(IV)
•
Children and adolescents with type 1 diabetes should be informed that tooth decay and
gingivitis can be prevented and/or reversed by brushing and flossing teeth at least twice
a day to remove plaque from the surfaces of the teeth and gingivae.13(C)
• The mouth should be examined regularly (twice a year) for the presence of gingivitis or
periodontitis.13(C)
18. Adolescent Health Issues
• Health care professionals should be aware that glycaemic control is more difficult in
adolescents with type 1 diabetes.38;45(II)
• Adolescents with diabetes have specific health needs relating to physical, emotional,
psychological and socio-cultural stages of adolescence.7;133(C)
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•
•
•
•
•
•
The major risks faced by adolescents with diabetes include deterioration of glycaemic
control, risk-taking behaviour, hypoglycaemia, recurrent diabetic ketoacidosis and
accelerated microvascular complications.7(C)
The transition from a paediatric to an adult service for the adolescent with diabetes is
often difficult.134-140
Ideally the transfer to an adult service should be comprehensive and should
involve:138(IV)
A preparation phase which is planned well in advance by a special transition service
and the adolescent and family.
A formal transition phase to an adult clinic, with appropriate referral and clear
directions for the patient and family (eg in case of emergencies).
An evaluation phase.
Adolescents should be taught to do a blood glucose estimation immediately before
driving a car and to have rapidly absorbed carbohydrate (eg glucose tablets) readily
accessible and to take these at the first indication of hypoglycaemia.141;142(C)
Smoking should be actively discouraged in diabetes.143(C)
Adolescents with diabetes need to be warned about the dangers of alcohol as part of
their diabetes education.13;29(C)
Issues surrounding sexuality should be approached with confidentiality and
empathy.7(C)
Assessment of sexual activity and the need for contraception should be a routine part of
adolescent diabetes care.7;13(C)
Health care professionals should be aware that the incidence of eating disorders is
increased in males and females with type 1 diabetes144-146 and that adolescent females
with type 1 diabetes and anorexia nervosa have a significantly increased mortality rate
compared to patients with type 1 diabetes alone.147(IV)
Health care professionals should be aware that intentional reduction or omission of
insulin to achieve weight loss is common (so-called insulin purging).113;114(IV)
Health care professionals should be aware that increased levels of retinopathy have
been found in patients with type 1 diabetes and sub-clinical and clinical eating
disorders.115;145;148(IV)
Treatment of eating disorders should include medical, nutritional and psychological
therapy by an experienced multidisciplinary team.149;150(C)
19. School
• Parents/care-givers and teachers should be aware that discrimination or stigmatisation
is unacceptable.7(C)
• Parents/care-givers and teachers should be aware that diabetes should not be the cause
of non-participation in any school activity.7;13(C)
• Parents/care-givers should meet with the relevant school personnel as soon as
practicable to discuss the issues involved in the care of their child at school.7(C)
151
• An individual care plan should be developed and reviewed regularly. (C)
• Parents/care-givers and teachers should be aware how to recognise and treat
hypoglycaemia.7;13(C)
• An emergency supply of rapidly absorbed carbohydrate should be readily available in
the classroom or wherever the school activity is undertaken.7;13(C)
• During or following hypoglycaemia or suspected hypoglycaemia, a child must not be
expected to walk to a ‘medical room’ nor left unaccompanied.7;13(C)
• Parents/care-givers and teachers should be aware that cognitive function and mood may
be affected for some hours after hypoglycaemia.152;153(IV)
20
•
Parents/care-givers and teachers should be aware that decreased cognitive function may
occur when hyperglycaemia is present.154(II)
• Parents/care-givers and teachers should be aware that risk factors for cognitive
dysfunction include a history of hypoglycaemic seizures,92;96;97 early age of onset and
longer duration of diabetes.94;95;96;98;155;156(IV)
• Parents/care-givers, teachers and students should be aware that students with diabetes
sitting for the higher examinations may apply for special provisions.13(C)
20. Diabetes Camps for Children and Adolescents
• Diabetes camps should be an integral component of overall care and support for
diabetic children and adolescents in Australia.13;40(C)
7
• Diabetes camps must provide a safe environment for both campers and camp staff. (C)
• Camps should be organised using an agreed set of standards and protocols. Standards
and protocols should specify leader to camper ratios, levels of medical and paramedical
support, dietary routines, injection routines, hierarchy and responsibility of camp
organisers, leader and camper application processes, emergency and evacuation
protocols and indemnity arrangements.157(C)
• A standardised medical information form should be completed for each camper (by
his/her family and the managing physician) prior to attending diabetes camp.157(C)
21. Travelling and Holidays
• The detailed management of diabetes during visits to distant locations or foreign
countries should be discussed with the diabetes educator or the physician well before
the departure date.13;40(C)
• The detailed management of diabetes on long flights crossing many time zones should
be discussed with the diabetes educator or the physician well before the departure
date.13;40(C)
• The family should be advised to arrange enough insulin, syringes, pen needles,
glucometer, blood and urine test strips for the duration of the anticipated stay plus an
extra supply.13;40(C)
• The family should be advised to have insulin, glucagon and testing equipment readily
available in hand luggage, and to have essential supplies divided between two bags to
avoid complete loss in case one bag is lost.13;40(C)
• The child or adolescent with diabetes should be advised to have his/her own food
supply and not rely on airline meal times.13;40(C)
• The family should be advised that no major change to the insulin regimen is required
for north-south travel.40(C)
• The family should be advised that extra insulin may be required for westward travel as
the day will be much longer and extra meals will require extra doses of insulin.158(IV)
• The family should be advised that less insulin may be required during eastward travel
as the day is cut short and the time between injections decreases therefore requiring a
lower insulin dose.158(IV)
• Switching to a simplified regimen of pre-meal injections of short-acting insulin during
long haul flights should be considered as an option.159(IV)
22. Complementary and Alternative Medicine
• Complementary and alternative medicine may include medicinal (herbal remedies,
dietary supplements, vitamins and minerals, naturopathic and homeopathic remedies),
or non-medicinal remedies (such as chiropractic, osteopathy and naturopathy).160(C)
21
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•
•
•
•
Complementary and alternative medicine use is common within the
community.160;161(IV)
In order to improve clinical care health care professionals should aim to understand the
use of complementary and alternative medicine within the family context.162;163(C)
Families should be advised that no complementary and alternative medicine therapies
have been shown to cure diabetes or improve control.162(C)
Ketoacidosis and death have been described when insulin has been omitted as part of an
alternative treatment.164 Parents should be warned that insulin should never be
significantly reduced or omitted as part of an alternative treatment.(IV)
Families should be advised that complementary and alternative medicine therapies have
the potential for adverse effects and for interactions with conventional treatments or
other complementary and alternative medicine therapies.162(C)
Health care professionals are able to determine the constituents of any complementary
or alternative medicine by enquiries to poisons centres and quoting the medicine’s
AUST L or AUST R numbers.165 Drugs without an AUST L or AUST R number
should not be considered for use in hospital.163(C)
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2002
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diabetes. Diabetic Medicine 19:1009-1013, 2002
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26
Diabetes mellitus is the most common endocrine disease in childhood and adolescence. This
handbook will predominantly deal with the topic of type 1 diabetes, previously known as
insulin-dependent diabetes mellitus (IDDM). Fifty percent of individuals with type 1 diabetes
are diagnosed before the age of 16 years.
Definition
The World Health Organization (WHO) defines diabetes mellitus as a metabolic disorder of
multiple aetiologies characterised by chronic hyperglycaemia with disturbances of
carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin
action, or both.1
Type 1 diabetes is a chronic autoimmune disease in the vast majority and accounts for
over 90 percent of childhood and adolescent diabetes in Australia. T-cell mediated
destruction of the pancreatic beta cells leads to insulin deficiency.1
Susceptibility to autoimmune type 1 diabetes is determined by the interaction of multiple
genes, with HLA genes having the strongest known association. Progressive beta cell
destruction occurs at a variable rate and the disease becomes clinically symptomatic when
approximately 90 percent of the pancreatic beta cells are destroyed.2 Insulin deficiency then
manifests itself clinically as blood glucose levels rise to pathological levels. The onset of the
disease is predictable, especially in the relatives of affected individuals, using a combination
of auto-antibody measurements, intravenous glucose tolerance testing and genetic typing.3;4
The environmental triggers (chemical and/or viral) which start the process of autoimmune
destruction of the pancreatic beta cells remain largely unknown. The pathological processes
leading to type 1 diabetes are known to start from months to years before clinical symptoms
become manifest (see chapter 2).
Non-autoimmune type 1 diabetes has similar clinical features but is characterised by the
lack of auto-antibodies against the antigens in the islets of Langerhans (islet cell antibodiesICA), or beta cell antigens (anti- insulin, anti-GAD65 or anti-IA2 antibodies).1
Epidemiology
Epidemiological incidence studies define the ‘onset of type 1 diabetes’ by the date of the first
insulin injection because of the variable time between the onset of symptoms and diagnosis.
Figure 1 (data from the IDF Diabetes Atlas) shows annual incidence rates for childhood
type 1 diabetes (0-14 years age group) comparing different countries of the world.5
27
Figure 1.1: Annual Incidence Rates for Type 1 Diabetes (0-14 years age group)
Comparing Different Countries in the World
Source: International Diabetes Federation Diabetes Atlas 2003
Finland
Sardinia
Sweden
Canada
Norway
Kuwait
Denmark
U.K.
Australia (NSW)
Rep. of Ireland
New Zealand
Iceland
USA
Netherlands
Spain
Germany
Luxembourg
Belgium
Portugal
Bangladesh
Cyprus
Hungary
Italy
Austria
Greece
Slovenia
France
Brazil
Sudan
Russia
Poland
Israel
Algeria
Romania
Macedonia
Cuba
Japan
China (H.K.)
Korea
Fiji
* 17.8 per 100,000 population
0
5
10
15
20
25
Incidence Rate (cases per 100,000 population per year)
30
35
40
28
•
•
•
•
•
•
•
•
Incidence is expressed as the number of new cases per year per 100,000 children under
the age of 15 years.
There are significant variations in the incidence of childhood type 1 diabetes between
countries - ranging from 0.1/100,000 in Fiji to 37.4/100,000 in Finland.5;6
In Europe incidence rates show a close correlation with the frequency of HLA
susceptibility genes in the general population.7
The most recent data on the incidence of childhood diabetes in Australia indicate an
incidence of 17.8 per 100,000 from 1990-1996, with an annual increase in incidence of
3.2% per year since 1990.8
There are two peaks of age of onset, the major peak at 10-12 years and a smaller peak
at 5-6 years.9;10
A well documented rise in the incidence, especially in the group of those under the age
of 5 years, has been noted in many countries.11-13
A seasonal variation in the presentation of new cases is well described, with the peak
being in the winter months.14;15;16
Despite familial aggregation there is no recognisable pattern of inheritance.
The risk of diabetes to an identical twin of a patient with type 1 diabetes is about 36
percent,17 compared to a life-time risk of 6 percent for a sibling or offspring (up to
30 years of age) and 0.5 percent for the general population.18
Type 1 diabetes is transmitted less frequently to the offspring of diabetic women
than to those of diabetic men (1.3% compared with 6.1% of offspring).19
Classification
In 1979, the US National Diabetes Data Group (NDDG), and in 1980, the WHO produced
diagnostic criteria and a classification system for diabetes mellitus. This brought order to a
chaotic situation in which nomenclature varied and diagnostic criteria showed enormous
variations using different oral glucose loads. In 1985 WHO slightly modified their criteria to
coincide more closely with the NDDG values.
In 1997, the American Diabetes Association (ADA) published its recommendations on
new diagnostic criteria for diabetes. WHO convened a Consultation on the same subject in
December 1996 and published these in 1998 (table 1.1). In general, the ADA and WHO
groups reached similar conclusions.1;20
The terms Insulin Dependent Diabetes Mellitus (IDDM) and Non Insulin Dependent
Diabetes Mellitus (NIDDM) are no longer used as all forms of diabetes may require insulin
therapy at some stage.1
The new classification encompasses both clinical stages and aetiological types of diabetes
mellitus and other categories of hyperglycaemia.
Clinical Staging of Diabetes
The clinical staging of diabetes, regardless of its aetiology, reflects the new concepts that
diabetes progresses through several clinical stages during its natural history:21
• Normoglycaemia.
• Impaired glucose regulation (impaired fasting glycaemia or impaired glucose
tolerance).
• Diabetes mellitus.
Moreover, individual subjects may move from stage to stage in either direction. Persons who
have, or who are developing, diabetes mellitus can be categorised by the stage according to
29
clinical characteristics, even in the absence of information concerning the underlying
aetiology.
Aetiologic Classification of Diabetes
The classification by aetiological type results from improved understanding of the causes of
diabetes mellitus.1
Type 1 diabetes encompasses the cases which are primarily due to pancreatic islet betacell destruction and are prone to ketoacidosis. Type 1 includes those cases attributable to an
autoimmune process, as well as those for which neither an aetiology nor a pathogenesis is
known (ie idiopathic). It does not include those forms of beta-cell destruction or failure to
which specific causes can be assigned (eg cystic fibrosis, mitochondrial defects, etc.).
Type 2 diabetes includes the common major form of adult diabetes which results from
defect(s) in insulin secretion, almost always with a major contribution from insulin resistance.
The lean phenotype of type 2 diabetes mellitus in adults found in Japan and the Indian subcontinent may be very distinct from the more characteristic form of type 2 found in white
Caucasians which is associated with increased visceral fat. Not enough information is
available, however, to characterise such subjects separately.
Malnutrition-related diabetes (MRDM) has been deleted in the new classification.
Impaired Glucose Tolerance is now classified as a clinical stage of impaired glucose
regulation, since it can be observed in any hyperglycaemic disorder, and is itself not diabetes.
A clinical stage of Impaired Fasting Glycaemia has been introduced to classify individuals
who have fasting glucose values above the normal range, but below the level diagnostic of
diabetes.
Gestational Diabetes now encompasses the groups formerly classified as Gestational
Impaired Glucose Tolerance (GIGT) and Gestational Diabetes Mellitus (GDM).
Table 1.1: Aetiological Classification of Disorders of Glycaemia1
Type 1
(beta-cell destruction, usually leading to absolute insulin deficiency)
• Autoimmune
• Idiopathic
Type 2
(may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly secretory defect with or without insulin
resistance)
Other specific types (see Table 1.2)
Gestational diabetes
30
Table 1.2: Other Specific Types of Diabetes1
Genetic defects of beta-cell function
• MODY 1-6
• Mitochondrial DNA mutation
• Others
Genetic defects in insulin action
• Type A insulin resistance
• Leprechaunism
• Rabson-Mendenhall syndrome
• Lipoatrophic diabetes
• Others
Diseases of the exocrine pancreas
• Fibrocalculous pancreatopathy
• Pancreatitis
• Trauma / pancreatectomy
• Agenesis
• Cystic fibrosis
• Haemochromatosis/thalassaemia
• Others
Endocrinopathies
• Cushing syndrome
• Acromegaly
• Phaeochromocytoma
• Glucagonoma
• Hyperthyroidism
• Somatostatinoma
• Others
Drug- or chemical-induced
• Insulin deficiency (Alloxan, Streptozotocin, Vacor, L-Asparaginase,
Tacrolimus, Cyclosporin, Diazoxide, others)
• Insulin resistance (Glucocorticoids, Growth Hormone, Interferon-alpha,
others)
Infections
• Congenital rubella
• Cytomegalovirus
• Others
Uncommon forms of immune-mediated diabetes
• Insulin autoimmune syndrome (antibodies to insulin)
• Anti-insulin receptor antibodies
• ‘Stiff Man’ syndrome
• Polyendocrine autoimmune deficiencies APS I and II
• Others
Other genetic syndromes
• Wolfram, Down, Klinefelter, Turner, Myotonic dystrophy, Friedreich ataxia,
Prader Willi, Laurence-Moon-Biedl, Porphyria
31
Diagnostic Criteria for Diabetes in Childhood and Adolescence
Diagnostic criteria for diabetes are based on:1
• Blood glucose measurements.
and
• The presence or absence of symptoms.
According to these criteria a diagnosis of diabetes can be made if:
• The characteristic symptoms and signs are present.
and
• Fasting venous plasma glucose concentration is greater than or equal to 7.0 mmol/L,
and/or the random venous plasma glucose concentration taken at least 2 hours after
eating is greater than or equal to 11.1 mmol/L.
Diabetes in childhood usually presents with severe symptoms, very high blood glucose levels,
marked glycosuria, ketonuria and frequently with ketoacidosis. The diagnosis is usually
confirmed quickly by measurement of a marked elevation of the blood glucose level. In this
situation treatment is urgent. Waiting another day to confirm the hyperglycaemia is neither
necessary nor appropriate for diagnosis in such circumstances. (See chapter 2)
In the absence of symptoms of diabetes both of the aforementioned plasma glucose criteria
need to be met and repeated on another day for a diagnosis of diabetes to be made.
In presence of mild symptoms, the diagnosis of diabetes should never be made on the
basis of a single abnormal blood glucose value. Diagnosis may require continued observation
with a fasting blood glucose measurement, 2 hour post-prandial blood glucose levels and/or
an oral glucose tolerance test (OGTT). An OGTT should not be performed if diabetes can be
diagnosed using fasting, random or post-prandial criteria as excessive hyperglycaemia can
result.
If doubt remains, periodic re-testing should be undertaken until the diagnosis is
established.
Table 1.3: WHO Criteria Values for Diagnosis of Diabetes Mellitus and Other
Categories of Hyperglycaemia
Glucose concentration, mmol/L
Venous whole blood Capillary whole blood Venous plasma*
Diabetes Mellitus:
Fasting
6.1
6.1
7.0
Or
2-hr post glucose load 10.0
11.1
11.1
or both
Impaired Glucose
Tolerance (IGT):
Fasting (if measured) <6.1
<6.1
<7.0
And
2-h post glucose load
6.7 and <10.0
7.8 and <11.1
7.8 and <11.1
Impaired Fasting
Glycaemia (IFG):
Fasting
5.6 and <6.1
5.6 and <6.1
6.1 and <7.0
And (if measured)
2-h post glucose load
<6.7
<7.8
<7.8
* Corresponding values (mmol/L) for capillary plasma are: for Diabetes Mellitus, fasting 7.0, 2-h 12.2; for
Impaired Glucose Tolerance, fasting <7.0 and 2-h 8.9 and <12.2; and for Impaired Fasting Glycaemia 6.1 and
<7.0 and if measured, 2-h <8.9.
32
Oral Glucose Tolerance Test (OGTT)
An oral glucose tolerance test (OGTT) is rarely indicated in making the diagnosis of type 1
diabetes in childhood and adolescence. If doubt exists, it is easier to monitor the child or
adolescent regularly with urine testing for glycosuria and to perform a fasting plasma glucose
or post-prandial blood tests to detect hyperglycaemia.1
The OGTT is used more frequently in the evaluation of possible glucose intolerance in a
child or adolescent suspected of having the metabolic syndrome or type 2 diabetes. Typical
clinical scenarios include an obese adolescent with acanthosis nigricans, a girl with the
polycystic ovary syndrome, an obese child with a family history of type 2 diabetes or an
obese child from a high risk ethnic background for type 2 diabetes.
The dose of glucose used in the OGTT is 1.75 gm/kg of body weight to a maximum of 75
gm.1 The glucose load or partial hydrolysate of starch of equivalent carbohydrate content is
administered in 250-300 ml water over a 5 minute period.
The OGTT should be performed strictly under the following conditions:
• The child or adolescent should not be suffering from any obvious intercurrent illness or
be on any medication known to affect blood glucose levels.
• Venous plasma glucose levels are preferred instead of whole blood or capillary glucose
levels for which different criteria are used (see table 1.3).
• Glucose estimations should be performed in NATA accredited laboratory using
laboratory instrumentation rather than glucose meters for bedside or home use.
• Blood specimens should be collected using sodium oxalate, sodium/potassium EDTA
or heparin as anticoagulants and centrifuged immediately or kept on ice if there is
delay. This is necessary as the presence of cells reduces the glucose levels by 5 percent
per hour at room temperature. Alternatively the specimen can be collected into sodium
fluoride or sodium iodoacetate tubes, which inhibit glycolysis and prevent the
metabolism of glucose by cells.
• The test should be done in the morning after fasting overnight.
• The diet in the preceding 3 days should be high in carbohydrate.
Interpretation of OGTT
The major change recommended by the WHO and the American Diabetes Association in the
revised diagnostic criteria for diabetes mellitus is the lowering of the diagnostic value of the
fasting venous plasma glucose concentration to 7.0 mmol/ l, from the former level of 7.8
mmol/ l.1;20 It is important to note that different criteria apply for capillary whole blood,
venous whole blood and venous plasma. For whole blood, the proposed new level is 6.1
mmol /l, from the former 6.7 mmol/ l. It is recommended that venous plasma levels be used
for consistency.
Despite the fact that children tend to have lower blood glucose levels than adults, the
OGTT criteria used for a diagnosis of diabetes mellitus in children and adolescents are the
same as for adults ie
• Elevated fasting venous plasma glucose (7.0 mmol/L).
and/or
• Elevated venous plasma glucose at 2 hours (11.1 mmol/L).
IFG and IGT both indicate glucose intolerance but are not equivalent in that they measure
different parameters. IFG is a measure of disturbed carbohydrate metabolism in the basal
33
state whilst the IGT is a dynamic measure of carbohydrate intolerance after a standardised
glucose load.
Children and adolescents with a fasting venous plasma glucose 6.1 mmol/L and <7.0
mmol/L have impaired fasting glycaemia.
Children and adolescents with a fasting venous plasma glucose <7.0 mmol/L AND 2 hour
OGTT values between 7.8 and <11.1 mmol/L are classified as having impaired glucose
tolerance (IGT).
The American Diabetes Association has classified both IFG and IGT as being pre-diabetes
as both categories indicate a high risk of progressing to type 2 diabetes over the next 5-10
years. For IGT, the risk for progression to diabetes for adults, remaining IGT or reverting to
normal are all approximately 33% over 5-10 years.22
In borderline diagnostic situations the presence of autoimmune markers such as antibodies
against islet cell antigens (ICA), IA-2 and GAD are of assistance in confirming type 1
diabetes. In type 1 diabetes, insulin and C-Peptide levels taken during the OGTT are low for
the accompanying blood glucose levels, whereas in type 2 diabetes they are usually elevated.
Intravenous Glucose Tolerance Test (IVGTT)
The IVGTT is a research tool. Interpretation of the test can be difficult.
The main use of IVGTT is to measure the early insulin response following an intravenous
glucose load.
In type 1 diabetes intervention studies, the IVGTT responses help to determine insulin
reserve in pre-diabetic individuals with elevated islet antibodies and other autoimmune
markers.
In studies of the metabolic syndrome (including IFG and IGT), the IVGTT is used to
obtain measures of insulin sensitivity, glucose disposal and beta cell function (minimal
model).23
Metabolic Syndrome
Although there is no international consensus on the definition of the Metabolic Syndrome, the
WHO has suggested the following working definition for adults. The Metabolic Syndrome
consists of glucose intolerance (impaired glucose tolerance or diabetes mellitus) and/or
insulin resistance with two or more of the following:1
• Raised arterial blood pressure 140/90 mmHg.
• Raised plasma triglycerides and/or low HDL cholesterol.
• Central obesity (males: waist to hip ratio >0.90; females: waist to hip ratio >0.85)
and/or BMI >30 kg/m2.
• Microalbuminuria (urinary albumin excretion rate 20 µg/min or albumin:creatinine
ratio 30 mg/g or >2.5 mg/mmol.
Other components not necessary for the recognition of the condition include
hyperuricaemia and coagulation disorders.
Persons with hypertension, central obesity, and dyslipidaemia, with or without
hyperglycaemia, are at high risk of macrovascular disease. Management should include
controlling blood glucose, and reducing the other cardiovascular risk factors (dyslipidaemia,
hypertension, smoking, obesity and hypercoagulability).
34
Type 2 Diabetes
Type 2 diabetes is rapidly increasing in children and adolescents, accounting for
approximately 5 percent of diabetes in this age group in Australia.24 The aetiology is
unknown. There may be predominantly insulin resistance with relative insulin deficiency or a
predominantly secretory defect (non-autoimmune mediated) with or without insulin
resistance.
The possibility of type 2 diabetes should be considered in children and adolescents who:
• Are obese.
• Have a strong family history of type 2 diabetes.
• Come from an ethnic background at high risk for diabetes.
• Produce little or no ketonuria.
• Show evidence of insulin resistance (acanthosis nigricans or polycystic ovary
syndrome).
The rising incidence of type 2 diabetes is associated with the epidemic of obesity.
Aborigines and Torres Strait Islanders are at high risk.25 Lifestyle factors such as little
exercise and overeating leading to obesity have profound effects. Whilst many indigenous
ethnic groups are liable to type 2 diabetes (eg Pima Indians in Arizona, Cree-Ojibee Indians
in Canada, Pacific islanders, Australian Aborigines, Torres Strait islanders), the increased
risk is now being seen in many populations (eg Indians and Indian communities originating
from the Indian subcontinent, Chinese, Africans, Afro-Americans, Arabs and HispanicAmerican).25 A positive family history for type 2 diabetes is present in over 80%. Identical
twins have a concordance rate for type 2 diabetes approaching 100 percent.26
Type 2 diabetes is often asymptomatic but may present with ketosis and even mild to
moderate ketoacidosis.27;28 It may be the underlying cause of hyperglycaemia associated with
infections and severe illness in some patients (see Stress Hyperglycaemia).
Treatment is difficult because of the chronicity and the need to incorporate lifestyle
changes. The long term microvascular complications of diabetes occur as frequently, as
quickly, and as severely as in type 1 diabetes.29 Because type 2 diabetes may have a
prolonged asymptomatic phase screening for complications should start at diagnosis or soon
after.31 The risks for macrovascular complications are also increased and reflect the
underlying Metabolic Syndrome in type 2 diabetes.
The principles of treatment for type 2 diabetes are:28
• Weight reduction if the patient is obese.
• Exercise and a healthy lifestyle.
• Carbohydrate- and fat-controlled diet.
• Metformin.
• Occasionally insulin replacement.
• Occasionally sulphonylurea or other oral hypoglycaemics.
• Occasionally insulin sensitisers (eg thiazolidinediones).
• Occasionally combination therapy of above medications.
• Control of associated macrovascular risk factors (hypertension, dyslipidemia, avoiding
smoking).
35
Screening for Type 2 Diabetes
Population screening for type 2 diabetes in children and adolescents cannot be justified in
Australia because of the low prevalence (in Japan, however, annual school glycosuria
screening programmes are in place). Targeted screening (fasting plasma glucose or 2 hour
post-prandial glucose) is recommended at the point of medical contact if high risk factors are
present (obesity, strong family history of type 2 diabetes, high risk ethnic group, acanthosis
nigricans, polycystic ovary syndrome).28;30;31 The Consensus Panel of the American Diabetes
Association recommends that testing of high risk subjects should be done every 2 years
starting at age 10 years or at onset of puberty, whichever is earlier.28
The World Health Organization states that opportunistic screening, as described above,
may be justified provided the individual being tested is appropriately informed and
counselled, and the health care system has the capacity to manage positive cases.32 There is
no indication for haphazard screening.32
Other Types of Diabetes
The possibility of other types of diabetes should be considered in children and adolescents
who:
• Have an autosomal dominant family history of diabetes.
• Have associated conditions such as deafness, optic atrophy or syndromic features.
• Have marked insulin resistance or require little or no insulin outside the partial
remission phase.
• Have been exposed to drugs known to be toxic to beta cells or cause insulin resistance.
Maturity Onset Diabetes of the Young (MODY)
Maturity onset diabetes of the young (MODY) is a disorder with the following
characteristics:33;34
• Onset before 25 years of age.
• Nonketotic diabetes mellitus.
• Autosomal dominant inheritance.
• Primary defect in the function of the pancreatic beta cells.
MODY is genetically heterogenous and includes at least 6 forms, all dominantly
inherited.33;34 There is great variation in the degree of hyperglycaemia, need for insulin and
risk for future complications. Apart from MODY 2, all other forms of MODY are due to
transcription factor gene mutations.33;34 It is likely that other genetic causes for the MODY
phenotype will be defined in the future. Gene diagnosis is now possible but expensive to
obtain.
• MODY 1- mutations of Hepatic Nuclear Factor-4 (HNF-4) gene on chromosome
20.33;34
• MODY 2 - mutations of the glucokinase gene (GCK) on the short arm of chromosome
7. Glucokinase is a beta cell enzyme which appears to function as the glucose sensor of
the beta cell. Patients with MODY 2 tend to present late, have mild hyperglycaemia, a
low risk for diabetes complications and may not require treatment (unless they are
homozygous for the condition).33;34
• MODY 3 - mutations of HNF-1 gene on chromosome 12. These patients have a
severe defect in insulin secretion and major hyperglycaemia.33;34
36
•
MODY 4 - mutations of IPF-1 (Insulin Promoter Factor-1) gene on chromosome 7.
Homozygous patients have pancreatic aplasia.33;34
33;34
• MODY 5 - mutations of HNF-1 gene on chromosome 17.
• MODY 6 - mutations of Neurogenic Differentiation Factor-1 (beta 2- NeuroD1)
gene.33;34
33;34
• MODY X - others.
Adults with MODY are liable to the same microvascular and macrovascular complications of
diabetes as patients with type 2 diabetes. Complications are rare in MODY 2.33;34
The principles of treatment in MODY are the same as for type 2 diabetes:
• Weight reduction if the patient is obese.
• Exercise and a healthy lifestyle.
• Carbohydrate- and fat-controlled diet.
• Sulphonylurea drugs or metformin (MODY 3 may be very sensitive to small doses of
sulphonylureas.34
• Insulin replacement.
DIDMOAD Syndrome (Wolfram Syndrome)
DIDMOAD syndrome (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, Deafness) is a
rare autosomal recessive condition associated with non-autoimmune degeneration of the
pancreatic beta cells.35 The Wolfram gene (WSF-1) has been cloned and is on chromosome 4.
Diabetes is usually the first manifestation and all cases reported also have optic atrophy.
Other manifestations are more variable and include:
• Diabetes mellitus (median age 8.2 years).
• Optic atrophy (median age 13.1 years).
• Diabetes insipidus (median age 14.1 years).
• Sensorineural deafness (median age 15.0 years).
• Neurological degeneration (with CNS atrophy on MRI).
• Psychiatric disturbances.
• Death (median age 28 years).
Mitochondrial Diabetes
Maternal transmission of mutated mitochondrial DNA (mtDNA) can result in maternally
inherited diabetes. Although several mutations have been implicated, the strongest evidence
relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNA
(leu(UUR)) gene. Mitochondrial diabetes is commonly associated with sensorineural
deafness and often presents with progressive non-autoimmune beta-cell failure.36
Neonatal Diabetes
Insulin-requiring hyperglycaemia in the first month of life is known as neonatal onset
diabetes mellitus. This rare condition (1/400,000 births) may be associated with intrauterine
growth retardation.37 Approximately half of the cases are temporary and have been associated
with paternal isodisomy of chromosome 6.38;39 The permanent cases are associated with
pancreatic aplasia, mutations of Insulin Promoter Factor-1 (chromosome 7), complete
glucokinase deficiency (chromosome 7)40 and mutations of the FOXP3 gene (T cell
regulatory gene) as part of the IPEX syndrome.41
37
Cystic Fibrosis and Diabetes
Diabetes in Cystic Fibrosis is primarily due to insulin deficiency. However, insulin resistance
secondary to infections and medications (bronchodilators and glucocorticoids) may
contribute significantly during acute illness. Diabetes tends to occur late in the disease,
typically in adolescence and early adulthood.42 Concurrent cirrhosis, if present, may
contribute to insulin resistance. The onset of diabetes is a poor prognostic sign. Poorly
controlled diabetes will interfere with immune responses to infection and promote
catabolism.
Screening recommendations vary from testing a random blood glucose level annually in
all children with cystic fibrosis 14years old, to performing an oral glucose tolerance test
annually in all those >10years old.42;43
Insulin therapy initially may only be needed during respiratory infections due to acute on
chronic infective episodes, but eventually ongoing therapy is frequently necessary. Initially
insulin doses are small (supplemental rather than total insulin replacement). In some patients,
early insulin therapy prior to symptoms of hyperglycaemia may provide metabolic effects
beneficial to growth, weight and pulmonary function.44;45
Drug Induced Diabetes
The most frequent scenarios for drug induced diabetes occur in neurosurgery, chemotherapy
for malignancies and immunosuppression post transplant.
In neurosurgery, large doses of dexamethasone are frequently used to prevent cerebral
oedema (eg dexamethasone 24 mg per day). The additional stress of the surgery may add to
the drug-induced insulin resistance, and cause a relative insulin deficiency, sufficient to cause
a transient form of diabetes. This will be exacerbated if large volumes of intravenous
dextrose are given for diabetes insipidus. An intravenous insulin infusion is the optimal way
to control the hyperglycaemia which is usually transient.
In oncology, protocols which employ L-asparaginase, high dose glucocorticoids,
cyclosporin or tacrolimus (FK506) may be associated with diabetes. L-asparaginase usually
causes a reversible form of diabetes.46 Tacrolimus and cyclosporin may cause a permanent
form of diabetes possibly due to islet cell destruction.47 Often the diabetes is cyclic and
associated with the chemotherapy cycles, especially if associated with large doses of
glucocorticoids.
In transplantation medicine, secondary diabetes most frequently occurs with the use of
high dose steroids and tacrolimus.48;49
Stress Hyperglycaemia
Stress hyperglycaemia is hyperglycaemia detected in the presence of fever, infection, surgery,
respiratory distress, head trauma, or other stress. It is usually transitory and should not be
regarded as diagnostic of diabetes.1
One large study describes the occurrence of stress hyperglycaemia in up to 5% of children
presenting to an emergency department with acute illness or injury, and identifies traumatic
injuries, febrile seizures and elevated body temperature (>39 degrees) as the most commonly
associated features.50 Of 41 children with stress hyperglycaemia, none had developed
diabetes after a mean follow-up period of 3.5years. In other smaller studies, the reported
incidence of progressing to overt diabetes varied from 0% to 33%.51-56 Children who develop
hyperglycaemia without a serious illness are more likely to develop diabetes than those who
have hyperglycaemia in response to a serious illness.53
38
Follow-up of patients with a history of stress hyperglycaemia varies from centre to centre.
Autoantibody screening for antipancreatic antibodies is a practical and useful method of
follow-up. Islet cell antibodies and insulin autoantibodies have a high positive predictive
value for type 1 diabetes in children with stress hyperglycaemia.53
The Evidence
The evidence on the prevalence/incidence of type 1 diabetes in children in Australia and
worldwide is shown in Evidence table 1.1.
• Worldwide the incidence of type 1 diabetes in children under the age of 15 ranges from
0.1 - 37.4 per 100,000.5;6(IV)
• The most recent data on the incidence of childhood type 1 diabetes in Australia (New
South Wales) indicates an incidence of 17.8 per 100,000 from 1990-1996, with an annual
increase in incidence of 3.2% per year since 1990.8;16 (IV)
Additional Technical Reports and Consensus Statements used to formulate the
recommendations and principles of clinical practice are listed in Evidence table 1.2.
Recommendations and Principles
• The diagnosis of diabetes in children and adolescents should be based on the World Health
Organization criteria (1999).1(T)
• Worldwide the incidence of type 1 diabetes in childhood varies greatly (0.1 - 37.4 per
100,000), with the Australian incidence being 17.8 and increasing by 3.2% per year since
1990.5;6;8;16(IV)
• Diabetes can be diagnosed if the characteristic symptoms and signs are present and fasting
venous plasma glucose concentration is greater than or equal to 7.0 mmol/L, and/or the
random venous plasma glucose concentration taken at least 2 hours after eating is greater
than or equal to 11.1 mmol/L.1(T)
• The possibility of type 2 diabetes should be considered in children and adolescents who
are obese, have a strong family history of type 2 diabetes, come from an ethnic
background at high risk for diabetes, produce little or no ketonuria and show evidence of
insulin resistance (acanthosis nigricans or polycystic ovary syndrome).1;28(T,C)
• The possibility of other types of diabetes should be considered in children and adolescents
who have any of the following: an autosomal dominant family history of diabetes, have
associated conditions such as deafness, optic atrophy or syndromic features, have marked
insulin resistance or require little or no insulin outside the partial remission phase or have
been exposed to drugs known to be toxic to beta cells or cause insulin resistance.1;57(T,C)
• An oral glucose tolerance test (OGTT) is rarely indicated in making the diagnosis of type
1 diabetes in childhood and adolescence.1;57(T,C)
• The OGTT may be used in the evaluation of possible glucose intolerance in a child or
adolescent suspected of having the metabolic syndrome eg an obese adolescent with
acanthosis nigricans, a girl with the polycystic ovary syndrome, an obese child with a
family history of type 2 diabetes or an obese child from a high risk ethnic background for
type 2 diabetes.28;32(T,C)
• Targeted screening for type 2 diabetes (fasting plasma glucose or 2 hour post-prandial
glucose) is recommended at the point of medical contact if high risk factors are present
(obesity, strong family history of type 2 diabetes, high risk ethnic group, acanthosis
nigricans, polycystic ovary syndrome) and every 2 years thereafter.31;32(T,C)
IV = Evidence from case series, either post-test or pre-test and post-test
T = WHO technical report produced by expert panels
C = Consensus statement endorsed by professional organisations
39
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35. Barrett TG, Bundey SE: Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet
346:1458-1463, 1995
36. Alcolado JC, Laji K, Gill-Randall R: Maternal transmission of diabetes. Diabetic Medicine 19:89-98, 2002
37. von Muhlendahl KE, Herkenhoff H: Long-term course of neonatal diabetes. New England Journal of Medicine 333:704-708, 1995
38. Hermann R, Laine AP, Johansson C, Niederland T, Tokarska L, Dziatkowiak H, Ilonen J, Soltesz G: Transient but not permanent
neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6. Pediatrics 105:49-52, 2000
40
39. Metz C, Cave H, Bertrand AM, Deffert C, Gueguen-Giroux B, Czernichow P, Polak M: NDM French Study Group: Neonatal
diabetes mellitus. Neonatal diabetes mellitus: chromosomal analysis in transient and permanent cases. Journal of Pediatrics 141:483489, 2002
40. Njolstad PR, Sovik O, Cuesta-Munoz A, Bjorkhaug L, Massa O, Barbetti F, Undlien DE, Shiota C, Magnuson MA, Molven A,
Matschinsky FM, Bell GI: Neonatal diabetes mellitus due to complete glucokinase deficiency. New England Journal of Medicine
344:1588-1592, 2001
41. Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, Kelly T, Saulsbury FT, Chance PF, Ochs HD: The
immune dysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature
Genetics 27:20-21, 2001
42. Riggs AC, Seaquist ER, Moran A: Guidelines for the diagnosis and therapy of diabetes mellitus in cystic fibrosis. Current Opinion in
Pulmonary Medicine 5:378-382, 1999
43. Lanng S, Hansen A, Thorsteinsson B, Nerup J, Koch C: Glucose tolerance in patients with cystic fibrosis: five year prospective study.
British Medical Journal 311:655-659, 1995
44. Dobson L, Hattersley AT, Tiley S, Elworthy S, Oades PJ, Sheldon CD: Clinical improvement in cystic fibrosis with early insulin
treatment. Archives of Disease in Childhood 87:430-431, 2002
45. Nousia-Arvanitakis S, Galli-Tsinopoulou A, Karamouzis M: Insulin improves clinical status of patients with cystic-fibrosis-related
diabetes mellitus. Acta Paediatrica 90:515-519, 2001
46. Pui CH, Burghen GA, Bowman WP, Aur RJ: Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and
prednisone. Journal of Pediatrics 99:46-50, 1981
47. Drachenberg CB, Klassen DK, Weir MR, Wiland A, Fink JC, Bartlett ST, Cangro CB, Blahut S, Papadimitriou JC: Islet cell damage
associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation.
Transplantation 68:396-402, 1999
48. Maes BD, Kuypers D, Messiaen T, Evenepoel P, Mathieu C, Coosemans W, Pirenne J, Vanrenterghem YF: Posttransplantation
diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors. Transplantation 72:1655-1661,
2001
49. Al-Uzri A, Stablein DM, A Cohn R: Posttransplant diabetes mellitus in pediatric renal transplant recipients: a report of the North
American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 72:1020-1024, 2001
50. Valerio G, Franzese A, Carlin E, Pecile P, Perini R, Tenore A: High prevalence of stress hyperglycaemia in children with febrile
seizures and traumatic injuries. Acta Paediatrica 90:618-622, 2001
51. Shehadeh N, On A, Kessel I, Perlman R, Even L, Naveh T, Soloveichik L, Etzioni A: Stress hyperglycemia and the risk for the
development of type 1 diabetes. Journal of Pediatric Endocrinology & Metabolism 10:283-286, 1997
52. Bhisitkul DM, Vinik AI, Morrow AL, She JX, Shults J, Powers AC, Maclaren NK: Prediabetic markers in children with stress
hyperglycemia. Archives of Pediatrics & Adolescent Medicine 150:936-941, 1996
53. Herskowitz-Dumont R, Wolfsdorf JI, Jackson RA, Eisenbarth GS: Distinction between transient hyperglycemia and early insulindependent diabetes mellitus in childhood: a prospective study of incidence and prognostic factors. Journal of Pediatrics 123:347-354,
1993
54. Schatz DA, Kowa H, Winter WE, Riley WJ: Natural history of incidental hyperglycemia and glycosuria of childhood. Journal of
Pediatrics 115:676-680, 1989
55. Herskowitz RD, Wolfsdorf JI, Ricker AT, Vardi P, Dib S, Soeldner JS, Eisenbarth GS: Transient hyperglycemia in childhood:
identification of a subgroup with imminent diabetes mellitus. Diabetes Research 9:161-167, 1988
56. Vardi P, Shehade N, Etzioni A, Herskovits T, Soloveizik L, Shmuel Z, Golan D, Barzilai D, Benderly A: Stress hyperglycemia in
childhood: a very high risk group for the development of type I diabetes. Journal of Pediatrics 117:75-77, 1990
57. International Society for Pediatric and Adolescent Diabetes: ISPAD Consensus Guidelines for the Management of Type 1 Diabetes
41
Chapter 2: Phases of Diabetes
Type 1 diabetes is characterised by:
• Preclinical diabetes.
• Presentation of diabetes.
• Partial remission or honeymoon phase.
• Chronic phase of lifelong dependency on administered insulin.
Preclinical Diabetes
Preclinical diabetes refers to the months or years preceding the clinical presentation of type 1
diabetes when islet antibodies can be detected as markers of beta cell autoimmunity. In
addition to these immunological markers, the risk of type 1 diabetes can further be
determined by genetic markers. The parameters currently helping to define the preclinical
phase include:
• Islet cell autoantibodies.
• Glutamic acid decarboxylase autoantibodies (65K GAD isoform).
• IA2 (also known as ICA 512 or tyrosine phosphatase) autoantibodies.
• Insulin autoantibodies.
• HLA typing.
Risks of progression to diabetes
Genetic markers conferring increased or decreased risk include:
a) HLA DR3 - DQA1*0501 - DQB1* 0201 (susceptible genotype).
b) HLA DR4 - DQA1*0301 - DQB1* 0302 (susceptible genotype).
c) HLA DR2 - DQA1*0102 - DQB1* 0602 (protective genotype).
Islet autoimmunity can be transient and one raised islet antibody alone has little prognostic
value.1-3 If an individual is under 45 years and does not have HLA DR2 - DQA1*0102 DQB1* 0602 then:
• Impaired first phase insulin release on intravenous glucose tolerance testing confers a
60% risk over the next 5 years.4
• Two or more islet antibodies raised without impaired first phase insulin release confer a
25-50% risk over the next 5 years.5;6
Neither screening of any population nor intervention in the preclinical phase should occur
outside the context of defined clinical studies.7 Individuals who screen positive for genetic or
immunological markers of type 1 diabetes should have access to appropriate counselling and
to centres participating in intervention and other defined studies. Intervention studies should
be registered as part of an international network of investigation and information about
ongoing studies should be readily available.7
To date, all clinical trials attempting to prevent or delay the onset of type 1 diabetes in those
at high risk have been unsuccessful. The most important of these intervention studies are:
• European Nicotinamide Diabetes Intervention Trial (ENDIT), a multinational
randomised placebo-controlled, double blinded intervention study, in which
nicotinamide did not delay or prevent the onset of type 1 diabetes in high-risk firstdegree relatives.8
• Diabetes Prevention Trial (DPT), in which low dose subcutaneous insulin therapy did
not delay or prevent the onset of clinical diabetes in first-degree relatives.4
42
The one proven environmental trigger of type 1 diabetes is congenital rubella.9;10 Other
potential environmental triggers are enteroviral infections (particularly coxsackie) and ECHO
viruses), casein, cow’s milk protein and gluten. Low levels of intercurrent infection and
improved hygiene may be associated with increased risk. International trials following
children at increased genetic risk from birth are investigating potential trigger and protective
factors.11;12
Presentation of Type 1 Diabetes
Prospective follow-up of high-risk subjects shows that diagnosis of type 1 diabetes can be
made in asymptomatic individuals in the majority of cases.4 In the Diabetes Prevention Trial
(DPT), when high-risk individuals were followed up, 73% of participants who were
diagnosed with diabetes were asymptomatic.4
A child presenting with a classical history of increasing polyuria, polydipsia and weight
loss over 2-6 weeks does not usually pose a diagnostic difficulty. Failure to consider the
possibility of diabetes or atypical presentations may result in late diagnosis.
Some children may have a rapid onset of symptoms and present within a few days in
diabetic ketoacidosis, but others may have a slow onset of symptoms over several months.
Urinary ‘dipstick’ testing for glycosuria and ketonuria provides a simple and sensitive tool
for excluding diabetes with less typical presentation. A blood glucose measurement (plasma
glucose >11.1 mmol/L) would confirm the diagnosis. The blood glucose measurement should
be a laboratory estimation rather than a bedside reading.
Non-emergency presentations
Non-emergency presentations of diabetes include:
• Recent onset of enuresis in a previously toilet-trained child, which may be
misdiagnosed as a urinary tract infection or the result of excessive fluid ingestion.
• Vaginal candidiasis, especially in prepubertal girls.
• Vomiting, which may be misdiagnosed as gastroenteritis.
• Chronic weight loss or failure to gain weight in a growing child.
• Irritability and decreasing school performance.
• Recurrent skin infections.
Emergency presentations
The usual emergency presentation of diabetic ketoacidosis in a child or adolescent includes
the following clinical features:
• Severe dehydration.
• Shock (rapid pulse rate, poor peripheral circulation, mottling and peripheral cyanosis).
• Hypotension (a late sign and rare in children with diabetic ketoacidosis).
• Frequent vomiting.
• Continuing polyuria despite the presence of dehydration.
• Weight loss due to fluid loss and loss of muscle and fat.
• Flushed cheeks due to the ketoacidosis.
• Acetone detected on the breath.
• Hyperventilation of diabetic ketoacidosis (Kussmaul respiration) is characterised by a
high respiratory rate and large tidal volume of each breath, which gives it a sighing
quality.
• Disordered sensorium (disoriented, semicomatose or rarely comatose).
43
Diagnostic difficulties leading to late diagnosis
The following situations may result in a late diagnosis of diabetic ketoacidosis:
• The very young child may present in severe ketoacidosis because of a more rapid onset
of severe insulin deficiency13 and because the diagnosis was not considered early.
• The hyperventilation of ketoacidosis may be misdiagnosed as pneumonia or asthma
(cough and breathlessness distinguish these conditions from diabetic ketoacidosis).
• The abdominal pain associated with ketoacidosis may simulate an acute abdomen and
lead to referral to a surgeon.
• The polyuria and enuresis may be misdiagnosed as a urinary tract infection.
• The polydipsia may be thought to be psychogenic.
• The vomiting may be misdiagnosed as due to gastroenteritis or sepsis.
Untreated, diabetic ketoacidosis is fatal. Therapy is urgent and referral to specialised services
is essential.
Differentiating between type 1 and type 2 diabetes at diagnosis
Features suggesting the diagnosis of type 2 diabetes rather than type 1 diabetes at diagnosis
are:14;15
• Obesity.
• Strong family history of type 2 diabetes.
• Acanthosis nigricans.
• High risk racial or ethnic group.
• Undetectable islet antibodies.
• Normal to high C-Peptide levels.
Partial Remission or Honeymoon Phase
In approximately 80 percent of children and adolescents, insulin requirements decrease
transiently following initiation of treatment.16
Most studies define a partial remission phase as that when the patient requires less than 0.5
units of insulin per kg of body weight per day and has a HbA1c <7%.16
The partial remission phase commences within days or weeks of the start of insulin
therapy and may last for weeks to months. During this phase blood glucose levels are
frequently stable within the normal range, despite fluctuations in diet and exercise. It is
important for the families to be advised of the transient nature of the partial remission phase
so as to avoid the false hope that the diabetes is spontaneously remitting.
Intensive therapy (continuous subcutaneous insulin infusion) has not been shown to
prolong the partial remission phase.17
In a few children and adolescents, requirements for insulin may decrease to the point of
being able to withdraw insulin therapy temporarily and still maintain normoglycaemia. As
low dose subcutaneous insulin therapy does not prolong residual beta cell function in the
preclinical phase,4 it is unlikely to do so in the remission phase. Therefore, continuing insulin
seems unlikely to prolong endogenous insulin production, or provide any other advantage
other than maintaining established diabetes routines for the child.
Ketoacidosis at presentation18 and young age16 reduce the likelihood of a remission phase.
Chronic Phase of Lifelong Dependence on Insulin
The progression from the partial remission phase into the chronic phase of lifelong
dependence on insulin is usually gradual but can be accelerated by an intercurrent illness.
44
Exogenous insulin replacement remains the only form of replacement therapy for children
and adolescents with type 1 diabetes. As mentioned in the previous section whilst intensive
therapy for type 1 diabetes has not been shown to prolong the partial remission phase there is
evidence it helps sustain some endogenous insulin secretion (measured by C-Peptide level),
which, in turn, is associated with better metabolic control.19 Intervention trials from diagnosis
are in progress as part of an international network of intervention trials to preserve beta cell
function either in the pre-clinical phase or from diagnosis.
Transplantation
Islet transplantation has become more successful since the introduction of less beta cell toxic
immunosuppressive agents and refined techniques to harvest adequate numbers of viable beta
cells.20 The numbers of subjects who remain insulin independent falls with follow-up and
several donor pancreases are required for adequate beta cell numbers in the transplant.21 The
induction of immunologic tolerance without the need for chronic immunosuppressive therapy
is a major goal and the potential use of haematopoietic stem cell therapy for induction of
tolerance and islet cell neogenesis in vitro are rapidly expanding research directions.
Pancreas transplantation provides high rates of graft survival at 1 year but there are
significant surgical risks and the requirement for long term immunosuppression precludes its
use in children and adolescents.22
The Evidence
The evidence on intervention trials to delay or prevent the onset of type 1 diabetes is listed in
Evidence Table 2.1.
• European Nicotinamide Diabetes Intervention Trial (ENDIT), a multinational quasirandomised placebo-controlled, double blinded intervention study, demonstrated that
nicotinamide did not delay or prevent the onset of type 1 diabetes in high-risk first-degree
relatives.8(III-1)
• The National Institute of Health Diabetes Prevention Trial (DPT) demonstrated in a
randomised controlled trial that low dose subcutaneous insulin therapy did not delay or
prevent the onset of clinical diabetes in high-risk first-degree relatives.4(II)
• Health care professionals should be aware that there are no interventions shown to delay
or prevent the onset of type 1 diabetes.4;8(II)
• Neither screening of any population nor intervention in the preclinical phase should occur
outside the context of defined clinical studies.7(C)
• Type 1 diabetes is characterised by a preclinical, clinical, partial remission and chronic
phase.23(C)
• Clinical presentation of diabetes can vary from non-emergency presentations (eg
polydipsia, polyuria, weight loss, enuresis) to severe dehydration, shock and diabetic
ketoacidosis.23;24(C,T)
• Parents and children with type 1 diabetes should be informed that the partial remission
phase of diabetes is transient and does not indicate remission of diabetes.23(C)
II = NHMRC Level II: Evidence from at least one properly-designed RCT
IV = Evidence obtained from case series
T = WHO technical reports produced by expert panels
C = Consensus statements endorsed by professional organisations
45
Reference List
1. Colman PG, Steele C, Couper JJ, Beresford SJ, Powell T, Kewming K, Pollard A, Gellert S, Tait B, Honeyman M, Harrison LC: Islet
autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody. Diabetologia
43:203-209, 2000
2. Kimpimaki T, Kulmala P, Savola K, Kupila A, Korhonen S, Simell T, Ilonen J, Simell O, Knip M: Natural history of beta-cell
autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population.
Journal of Clinical Endocrinology & Metabolism 87:4572-4579, 2002
3. Knip M: Natural course of preclinical type 1 diabetes. Hormone Research 57:6-11, 2002
4. Diabetes Prevention Trial-Type 1 Diabetes Study Group: Effects of Insulin in Relatives of Patients with Type 1 Diabetes Mellitus.
New England Journal of Medicine 346:1685-1691, 2002
5. Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT, Bottazzo GF, Gale EA: Combined analysis of
autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 43:1304-1310, 1994
6. Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, Chase HP, Eisenbarth GS: Prediction of type I diabetes in firstdegree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45:926-933, 1996
7. American Diabetes Association: Prevention of Type 1 Diabetes Mellitus. Diabetes Care 26:140, 2003
8. The European Nicotinamide Diabetes Intervention Trial (ENDIT) Group: Intervening before the onset of Type 1 diabetes: baseline
data from the European Nicotinamide Diabetes Intervention Trial. Diabetologia 46(3):339-46, 2003
9. Ginsberg-Fellner F, Witt ME, Fedun B, Taub F, Dobersen MJ, McEvoy RC, Cooper LZ, Notkins AL, Rubinstein P: Diabetes mellitus
and autoimmunity in patients with the congenital rubella syndrome. Reviews of Infectious Diseases 7 Suppl 1:S170-S176, 1985
10. McIntosh ED, Menser MA: A fifty-year follow-up of congenital rubella. Lancet 340:414-415, 1992
11. Juvenile Diabetes Research Foundation (JDRF) Center for Prevention of Type 1 Diabetes in Finland. Type 1 Diabetes Prediction and
Prevention Project (DIPP). http://www.utu.fi/research/dipp/ 2003.
12. TRIGR study group. Trial to reduce IDDM in the Genetically at risk (TRIGR) 2003. http://www.trigr.org/ Ref Type: Electronic
Citation
13. Keskinen PK: First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes.
Diabetologia 45:1639-1648, 2002
14. American Diabetes Association: Type 2 Diabetes in Children and Adolescents. Pediatrics 105:671-680, 2000
15. American Diabetes Association: Screening for Type 2 Diabetes. Diabetes Care 26:21-24, 2003
16. Lombardo F, Valenzise M, Wasniewska M, Messina MF, Ruggeri C, Arrigo T, De Luca F: Two-year prospective evaluation of the
factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: the key-role of age at
diagnosis. Diabetes, Nutrition & Metabolism - Clinical & Experimental 15:246-251, 2002
17. de Beaufort CE, Houtzagers CM, Bruining GJ, Aarsen RS, den Boer NC, Grose WF, van Strik R, de Visser JJ: Continuous
subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up
of a randomized, prospective trial. Diabetic Medicine 6:766-771, 1989
18. Bober E, Dundar B, Buyukgebiz A: Partial remission phase and metabolic control in type 1 diabetes mellitus in children and
adolescents. Journal of Pediatric Endocrinology & Metabolism 14:435-441, 2001
19. The Diabetes Control and Complications Trial Research Group: Effect of intensive therapy on residual beta-cell function in patients
with type 1 diabetes in the diabetes control and complications trial. A randomized controlled trial. Annals of Internal Medicine
128:517-523, 1998
20. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven
patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New England Journal of Medicine
343:230-238, 2000
21. Ryan EA, Lakey JR, Paty BW, Imes S, Korbutt GS, Kneteman NM, Bigam D, Rajotte RV, Shapiro AM: Successful islet
transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51:2148-2157, 2002
22. Odorico JS, Sollinger HW: Technical and immunosuppressive advances in transplantation for insulin-dependent diabetes mellitus.
World Journal of Surgery 26:194-211, 2002
24. World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO
46
Chapter 3: Medical Management
Every child and adolescent with type 1 diabetes, including those from rural and remote areas,
deserves to have access to optimal medical management. A child cannot fight for these rights.
Health care professionals looking after children must make advocacy for the child one of
their key responsibilities.1;2
Suboptimal medical management leads to poor diabetes control which may impair growth,
delay puberty and lead to irreversible long-term diabetic microvascular and macrovascular
complications.3 Quality of life and life expectancy may be significantly reduced under these
circumstances.
Poor metabolic control, younger age of onset and lower socioeconomic group are
predictors of re-hospitalisation rates which may indicate poor adjustment to diabetes.4 These
outcomes occur for a variety of reasons but many are potentially preventable.
Aims of Diabetes Management
The aims of diabetes management are to have:
• Optimal psychosocial adjustment.
• Optimal metabolic (glycaemic) control.
• Normal growth and development.
• An individualised plan of diabetes care incorporating the particular needs of the child or
adolescent and the family.
Hospital versus Ambulatory Stabilisation
At diagnosis the decision should be made between hospital admission or ambulatory
initiation of treatment.
A systematic review and other studies have concluded that in appropriately chosen
patients there are no disadvantages of ambulatory management compared to inpatient
management of children and adolescents with newly diagnosed type 1 diabetes.5-12 Older
children and adolescents who develop diabetes but are not dehydrated or acidotic may be
successfully managed out of hospital if expert diabetes support teams are available.
The importance of expert care at diagnosis cannot be over-emphasised. In a questionnaire
survey parents reported that care provided by paediatricians without a special interest in
diabetes is more likely to result in a longer hospital admission, whilst parental satisfaction
with the outpatient care and school liaison is lower than in those cared for by paediatricians
with a special interest in diabetes.13
Relative contra-indications to ambulatory initiation of insulin therapy include:2;14
• Very young age (under 2 years).
• Ketoacidosis
• Dehydration (moderate or severe).
• Profound grief reaction in family.
• Geographic isolation.
• No telephone in the home.
• Language or other communication difficulties.
• Significant psychological or psychiatric problems within the family.
Children, if hospitalised, should be admitted to paediatric hospital wards.15 Following the
treatment of acidosis or dehydration it is often possible to continue management on an
47
ambulatory basis. Children should not be admitted to adult wards. Adolescents, if requiring
hospitalisation, should preferably be accommodated in adolescent wards. The parents should
always be allowed open and free access to their child at all times.
The Australian Diabetes Educators Association have published minimum national
standards for the ambulatory initiation of insulin.16 These standards are not specific to
paediatric care, however, they describe process standards required in Australia to initiate
insulin effectively and safely.16
Children and adolescents should have access to care by a multidisciplinary team trained in
childhood and adolescent diabetes.2;17-19 It should be recognised that the members of the
management team include the patient with diabetes and his/her family. The members of the
team are therefore:
• The patient and his/her family.
• Paediatric endocrinologist or physician trained in the care of children and adolescents
with diabetes.
• Diabetes educator.
• Dietitian.
• Psychologist/social worker.
Care provided by a specialised diabetes multidisciplinary team has been shown to result in:2025
•
•
•
•
•
Fewer days in hospital.
Higher level of diabetes self care practices.
Decreased re-admission rates.
Lower HbA1c.
Delayed development of complications.
After the initial period of diagnosis and education (when frequent contact may be required),
the child should be regularly reviewed throughout the year. This should be no less than 3-4
times per year), including one major annual review (paying particular attention to review of
regular growth data, blood pressure, puberty, associated conditions, nutrition and
complications) with the multidisciplinary team.2;18;19 More frequent reviews by expert teams
may result in improved control.26;27
Foundations of Diabetes Management
The foundations of successful diabetes management include:
• Diabetes education.
• Insulin replacement.
• Blood glucose monitoring.
• Nutritional plan.
• Psychological adjustment and wellbeing of the whole family.
In addition, exercise should be encouraged because of its beneficial effects on glycaemic
control and wellbeing.
Diabetes Education
Ideally diabetes and nutritional education should be provided by Credentialled Diabetes
Educators and dietitians who have undertaken specialised training in paediatric diabetes
48
education and nutrition.2 If specialised diabetes and nutritional education is not available,
options include transfer to a centre with the necessary expertise or shared care with such a
centre able to provide outreach support.
Educational interventions have beneficial effects on diabetes management outcomes.28
Education is a continuous process and should be provided to the child or adolescent and
their family at diagnosis and repeated as required at follow up. Diabetes education is more
than a transfer of knowledge and should aim to result in the appropriate behaviour changes
needed for achieving and maintaining diabetes control.
Education should also be appropriate to the age and developmental level of the child or
adolescent.
Initial diabetes education is usually with the educator and the child and parent, but
continuing education can be provided in group settings. The relative merits of individual
versus group education have not been studied. Diabetes education can either be provided in a
hospital setting or on an ambulatory basis if there are no contra-indications to day care.
Diabetes education should also be made available to other care-providers such as
grandparents, teachers and staff in childcare centres.
Education should be adapted to each individual’s age, maturity, stage of diabetes, lifestyle
and culture.1;2 The following topics should be covered:
• The cause of diabetes.
• Insulin storage.
• Insulin injection techniques.
• Blood glucose measurement.
• Insulin adjustment.
• Exercise.
• Psychological and family adjustment.
• Hypoglycaemia, prevention and its management.
• Diabetes management during illness.
• Travel.
• Diabetes and exercise.
• Dietetic principles.
• Contraception.
• Alcohol and Drugs.
• Diabetes complications.
When age appropriate
• Driving.
• Smoking.
Insulin Replacement Therapy
The terms ‘conventional’ and ‘intensive’ insulin replacement regimens are becoming
historical terms and are losing their meaning as the emphasis has shifted from simply
equating intensified management with the number of injections given. The aim is to achieve
the best possible control of glycaemia in all children and adolescents with diabetes. See
Chapter 5 for details of various insulin regimens.
Immunisation
It is recommended that children and adolescents with type 1 diabetes should be immunised
according to the Australian Standard Immunisation Schedule29 unless a contra-indication is
present. Diabetes is not a contra-indication to immunisation.
49
In addition to the routine immunisations, the use of the Influenza and Pneumococcal
vaccines is being evaluated in people with diabetes.30;31
Outreach Services
In rural and geographically remote areas with low population density and very small numbers
of children with diabetes, it may not be possible to provide a local multidisciplinary team. In
these situations, care may be successfully provided by a local paediatrician/physician with
access to resources, support and advice from a tertiary centre diabetes team.32;33
In an audit of almost 1200 children with type 1 diabetes living in New South Wales and
the Australian Capital Territory, there was no significant difference in glycaemic control
between those from urban and those from rural areas. HbA1c and the incidence of severe
hypoglycaemia were used as measures of glycaemic control. This audit confirmed
homogeneity of metabolic control regardless of location or system of care in NSW/ACT.32
Support to isolated patients may be in the form of outreach clinics or telemedicine
consultations including access to telephone support 24 hours a day and regular telephone
contact.32;34-36
Where local resources are lacking, the annual review should be performed by a tertiary
centre diabetes team.
Transition to Adult Services
The importance of an effective transition process for adolescents cannot be overemphasised
(see Chapter 18).
Cost Issues
The cost of hospitalisation for children and adolescents with type 1 diabetes in New South
Wales was estimated to be approximately $1.5 million per year in 1990.37 The management
of type 1 diabetes in children and adolescents with type 1 diabetes results is significant health
care costs at diagnosis and for subsequent readmissions to hospital.37 Since this analysis was
done ambulatory care at diagnosis has become more common, however no Australian study
has reassessed the cost implications of the changing pattern of care.
Two relevant studies were located addressing the cost of ambulatory care versus hospital care
at diagnosis. One RCT found that although ambulatory care increased hospital costs mainly
by increasing nursing consultation costs and the requirement for telephone support, this
increase was offset by significant cost savings for parents.38;39 Overall there was no
significant cost difference between the two modes of care. This study was in the Canadian
health care system and may not be directly applicable to the Australian setting. A second
study (also in Canada) retrospectively compared the costs of hospital care versus ambulatory
care and found that hospital costs were much higher for hospital care, however nurse
education, parental and societal costs were not accounted for.11
The Evidence
The evidence for the benefits of ambulatory care versus hospital inpatient care of patients
with newly diagnosed type 1 diabetes is listed in Evidence Table 3.1.
• A Cochrane systematic review and other studies have concluded that in appropriately
chosen patients there are no disadvantages of ambulatory management compared to
50
inpatient management of children and adolescents with newly diagnosed type 1 diabetes.512
(I)
The evidence comparing metabolic control in urban and rural children and adolescents with
type 1 diabetes is listed in Evidence Table 3.2.
• In a population based audit of children with type 1 diabetes living in New South Wales
and the Australian Capital Territory, there was no significant difference in glycaemic
control between those from urban and those from rural areas. This audit confirmed
homogeneity of metabolic control regardless of location or system of care in NSW/ACT.32
Similar results were obtained in an audit of Victorian urban and rural diabetic youths.33(IV)
The evidence on the effect of educational interventions on glycaemic control and
psychosocial outcome is listed in Evidence table 3.3.
• A Health Technology Assessment has concluded that educational interventions have
beneficial effects on diabetes management outcomes.28(I)
• Every child and adolescent with type 1 diabetes, including those from rural and remote
areas, should have access to optimal medical management.1;2;14(C)
• Health care professionals who look after children should make advocacy for the child one
of their key responsibilities.14(C)
• Older children and adolescents who develop diabetes but are not dehydrated or acidotic
may be considered for management out of hospital if expert diabetes support teams are
available.5-12(I)
• Relative contraindications to ambulatory initiation of insulin therapy include very young
age (under 2 years), ketoacidosis, dehydration (moderate or severe), geographic isolation,
no telephone at home, language or other communication difficulties, profound grief
reaction and significant psychological or psychiatric problems within the family.2;14(C)
• Children and adolescents with type 1 diabetes should have access to care by a
multidisciplinary team trained in childhood diabetes.2;17;18;19(C)
• The older child and the family should be recognised as being part of the management
team.(C)
• Diabetes education should be part of the management of type 1 diabetes in children and
adolescents. Educational interventions have beneficial effects on diabetes management
outcomes.28(I)
• Education should be adapted to each individual’s age, maturity, stage of diabetes, lifestyle
and culture.2(C)
• After the initial period of diagnosis and education (when frequent contact may be
required), the child should be regularly reviewed throughout the year. This should be no
less than 3-4 times per year), including one major annual review (paying particular
attention to growth, blood pressure, puberty, associated conditions, nutrition and
complications) with the multidisciplinary team.2;18;19(C)
• Children and adolescents with type 1 diabetes should be immunised according to the
Australian Standard Immunisation Schedule29 unless a contra-indication is present.
Diabetes is not a contra-indication to immunisation.(C)
• In rural and geographically remote areas within the Australian health care system, children
with diabetes may be successfully cared for by a local paediatrician/physician with
51
training and experience in paediatric diabetes access to resources, support and advice from
a tertiary centre diabetes team.32;33(IV)
I = Evidence obtained from a systematic review of all relevant randomized controlled trials
III-3 = Evidence from comparative studies with historical control, two or more single-arm studies, or interrupted time series
without a parallel control group
IV = Evidence obtained from case series, either post-test or pre-test and post-test
T = Technical Report
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International Diabetes Federation Consultative Section on Diabetes Education. International Curriculum for Diabetes Health
Professional Education. 2002. Brussels, International Diabetes Federation. Ref Type: Report
Charron-Prochownik D, Kovacs M, Obrosky DS, Stiffler L: Biomedical and psychosocial predictors of early rehospitalization
among children with insulin-dependent diabetes mellitus: a longitudinal study. Diabetic Medicine 11:372-377, 1994
Clar C, Waugh N, Thomas S: Routine hospital admission versus out-patient or home care in children at diagnosis of type 1 diabetes
mellitus. Cochrane Database of Systematic Reviews 2003
Srinivasan S, Craig ME, Beeney L, Hayes R, Harkin N, Ambler GR, Donaghue KC, Cowell CT: An ambulatory stabilisation
program for children with newly diagnosed type 1 diabetes. Medical Journal of Australia 180:277-280, 2004
Forsander GA SJPB: Influence of the initial management regimen and family social situation on glycemic control and medical care
in children with type 1 diabetes mellitus. Acta Paediatrica 89:1462-1468, 2000
Kirk J, Thomas E, McEvilly A, Shaw N: Extension of a pediatric diabetes home care service. Practical Diabetes International
20:125-128, 2003
Lee PD: An outpatient-focused program for childhood diabetes: design, implementation, and effectiveness. Texas Medicine 88:6468, 1992
Schneider AJ: Starting insulin therapy in children with newly diagnosed diabetes. American Journal of Diseases of Children
137:782-786, 1983
Spaulding RH, Spaulding WB: The diabetic day-care unit. II. Comparison of patients and costs of initiating insulin therapy in the
unit and a hospital. Canadian Medical Association Journal 114:780-783, 1976
Swift PG, Hearnshaw JR, Botha JL, Wright G, Raymond NT, Jamieson KF: A decade of diabetes: keeping children out of hospital.
Lessing DN, Swift PG, Metcalfe MA, Baum JD: Newly diagnosed diabetes: a study of parental satisfaction. Archives of Disease in
Childhood 67:1011-1013, 1992
Association for the Welfare of Child Health. Health Care Policy Relating to Children and their Families. 1999. Ref Type: Report
Australian Diabetes Educators Association. National Standards for the Development and Quality Assessment of Services Initiating
Insulin in the Ambulatory Setting. 2004.
Adolescents. 1998
Queensland Health: Best practice guidelines for the management of Type 1 Diabetes in children and Adolescents. 2002
Bloomfield S, Farquhar JW: Is a specialist paediatric diabetic clinic better? Archives of Disease in Childhood 65:139-140, 1990
Laron Z, Galatzer A, Amir S, Gil R, Karp M, Mimouni M: A multidisciplinary, comprehensive, ambulatory treatment scheme for
diabetes mellitus in children. Diabetes Care 2:342-348, 1979
Levetan CS, Salas JR, Wilets IF, Zumoff B: Impact of endocrine and diabetes team consultation on hospital length of stay for
patients with diabetes. American Journal of Medicine 99:22-28, 1995
Likitmaskul S, Wekawanich J, Wongarn R, Chaichanwatanakul K, Kiattisakthavee P, Nimkarn S, Prayongklin S, Weerakulwattana
L, Markmaitree D, Ritjarean Y, Pookpun W, Punnakanta L, Angsusingha K, Tuchinda C: Intensive diabetes education program and
multidisciplinary team approach in management of newly diagnosed type 1 diabetes mellitus: a greater patient benefit, experience at
Siriraj Hospital. Journal of the Medical Association of Thailand 85:S488-S495, 2002
Zgibor JC, Songer TJ, Kelsey SF, Weissfeld J, Drash AL, Becker D, Orchard TJ: The association of diabetes specialist care with
health care practices and glycemic control in patients with type 1 diabetes: A cross-sectional analysis from the Pittsburgh
Epidemiology of Diabetes Complications Study. Diabetes Care 23:472-476, 2000
Zgibor JC, Songer TJ, Kelsey SF, Drash AL, Orchard TJ: Influence of health care providers on the development of diabetes
complications: long-term follow-up from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 25:15841590, 2002
Dorchy H, Roggemans MP, Willems D: Glycated hemoglobin and related factors in diabetic children and adolescents under 18
years of age: a Belgian experience. Diabetes Care 20:2-6, 1997
American Diabetes Association: Immunization and the Prevention of Influenza and Pneumococcal Disease in People With Diabetes.
Diabetes Care 26:126S, 2003
52
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Smith SA, Poland GA: Use of influenza and pneumococcal vaccines in people with diabetes. Diabetes Care 23:95, 2000
GA: Regional and urban Victorian diabetic youth: clinical and quality-of-life outcomes. Journal of Paediatrics & Child Health
38:593-596, 2002
Biermann E, Dietrich W, Standl E: Telecare of diabetic patients with intensified insulin therapy. A randomized clinical trial. Studies
in Health Technology & Informatics 77:327-332, 2000
Gelfand KG: Intensive telehealth management of five at-risk adolescents with diabetes. Journal of Telemedicine & Telecare 9:117121, 2003
Howells L, Wilson AC, Skinner TC, Newton R, Morris AD, Greene SA: A randomized control trial of the effect of negotiated
telephone support on glycaemic control in young people with Type 1 diabetes. Diabetic Medicine 19:643-648, 2002
Sutton L, Plant AJ, Lyle DM: Services and cost of hospitalization for children and adolescents with insulin-dependent diabetes
mellitus in New South Wales. Medical Journal of Australia 152:130-136, 1990
Dougherty G, Schiffrin A, White D, Soderstrom L, Sufrategui M: Home-based management can achieve intensification costeffectively in type I diabetes. Pediatrics 103:122-128, 1999
Dougherty GE, Soderstrom L, Schiffrin A: An economic evaluation of home care for children with newly diagnosed diabetes:
results from a randomized controlled trial. Medical Care 36:586-598, 1998
53
Chapter 4: Insulin Preparations and Storage
Children and adolescents with type 1 diabetes are dependent on insulin for survival.1 There is
no alternative to treatment with insulin. Insulin is not normally used in combination with any
other hypoglycaemic agents.
Insulin Action
Despite the published data on the duration of action of the various insulin preparations there
is much inter- and intra-individual variation2 (see Table 4.1 and Figure 4.1). The onset, peak
effect and duration of insulin action may vary both between individuals and for the same
individual depending on a number of factors including:3-6
• Age.
• Fat mass.
• Pubertal stage.
• The dose of insulin used.
• The site of the injection.
• Exercise.
• Insulin concentration, type and formulation.
• Ambient and body temperature.
Types of Insulin
Until the development of recombinant DNA technology in the 1980s, insulin was purified
from porcine or beef pancreatic tissue. Human recombinant insulins are now the most widely
used forms and are the recommended first line preparations in the paediatric age group.
Human recombinant insulins are preferred because of their availability through modern
manufacturing techniques using recombinant DNA technology and because of their low
immunogenicity.
A Cochrane Collaboration systematic review of 45 RCT’s (including 4 paediatric studies)
found no significant differences in metabolic control or hypoglycaemic episodes between
animal or human insulins.7
Porcine insulins are now only available in Australia under the ‘Special Access Scheme’
(SAS) provisions. Requests for porcine insulin need to be forwarded to the Therapeutic
Goods Administration (TGA) before requesting the stock from the company. These insulins
are occasionally useful in children with allergic reactions attributable to human recombinant
insulin preparations.
Beef insulin is still available in Australia (isophane and short-acting). It is occasionally
tried in children with type 1 diabetes not able to be satisfactorily stabilised on human insulin.
The types of insulin currently available are outlined in the table below:
54
Table 4.1: Insulins Currently in Use in Australia
Insulin
Preparation
Human
Bovine
Analogue
Biphasic
Short-acting (neutral)
Intermediate-acting (isophane)
Intermediate-acting (lente)
Long-acting (ultralente)
Short-acting (neutral)
Intermediate-acting (isophane)
Rapid-acting
Basal (glargine)
Basal (detemir)*
Short-acting/intermediate
Onset of
Action (h)
0.5-1
1-2
1-2.5
4-8
0.5-1
2
0.25-0.5
2-4
1-2
0.5
Peak of
Action (h)
2-4
4-12
6-15
12-24
3-6
6-12
1-3
None
6-12
1-12
Duration of
Action (h)
5-8
16-24
24
20-30
6-8
18
3-5
24
20-24
16-24
0.5
1-12
16-24
Ratio 20/80
Ratio 30/70
Ratio 50/50
Rapid-acting analogue/intermediate
Ratio 25/75
Ratio 30/70
*Anticipated availability in 2004/2005
Rapid-acting insulin
Insulin has a tendency to aggregate into dimers and hexamers which retard the absorption and
biological availability. Insulin lispro and insulin aspart are now widely used rapid-acting
insulin analogues which prevent the insulin molecule from forming dimers or hexamers.
These monomeric insulins are clear solutions that have a very rapid onset of action, peak
within 1 hour and have duration of action of up to 5 hours.
In accordance with the manufacturers’ recommendations rapid-acting insulin should be
injected at the time of a meal.
Rapid-acting insulins are used in:
• Twice daily insulin regimens.
• Basal-bolus insulin regimens.
These analogues are effective in other specific situations such as:
• Rapid-acting insulin given at afternoon tea reduces high blood glucose levels
commonly seen before the evening meal in children and adolescents on twice daily
injections of rapid-acting or regular insulin in combination with an isophane insulin.8
• Rapid-acting insulin has been shown to be effective when given post-prandially in
prepubertal children with type 1 diabetes with unpredictable eating habits (eg infants,
toddlers and preschool children).9 However, its effect on post-prandial blood glucose
levels has been variable.10 The NICE Guidelines on Diagnosis and Management of
Type 1 Diabetes in Children and Young People have indicated that post-prandial
rapid–acting insulin is an option in the management of these patient groups.30
• Rapid-acting insulin analogues are used in continuous subcutaneous insulin infusion
(CSII) therapy.11;12
• Rapid-acting insulin analogues may also be used for the management of
hyperglycaemia and ketosis during sick days.
55
Short-acting insulin
Short-acting insulin is also known as ‘soluble’ or ‘regular’ insulin and is a clear solution. It is
used in the management of diabetic ketoacidosis and as a component of daily replacement
therapy. It can be used by itself as a pre-meal bolus injection in a basal-bolus regimen or in
combination with intermediate-acting insulin in a twice-daily injection regimen.
Data are inconsistent on the optimal timing of short-acting insulin in relation to meals.
However, in accordance with the manufacturers’ recommendations, short-acting insulin
should be injected 15-20 minutes before a meal. The American Diabetes Association
discourages eating within a few minutes after (or before) injecting short-acting insulin as the
likelihood of a rapid rise of blood glucose is increased and it may increase the risk of delayed
hypoglycaemia.13
Intermediate-acting insulin
These insulins are present in the form of a suspension and are therefore referred to as
‘cloudy’ insulins. Their time-course of action makes them suitable for twice-daily insulin
regimens and for pre-bed dosage in basal-bolus regimens. The vials need to be gently but
properly mixed prior to each use to ensure a uniform concentration. Pens containing isophane
need to be tipped at least 20 times for adequate mixing, however, vigorous mixing may cause
protein degradation.
The two principal preparations currently used are:
• Isophane or NPH (Neutral Protamine Hagedorn) insulins.
• Crystalline zinc-acetate insulins (lente insulins).
To avoid confusion and prescribing errors, the use of the terms ‘clear’ to describe rapidacting or short-acting insulin and ‘cloudy’ to describe intermediate- or long-acting insulin,
should be discouraged as the long-acting insulin analogues, glargine and detemir, are clear
solutions.
Long-acting insulins
These preparations may be used to meet basal insulin requirements, especially in basal bolus
injection regimens.
Basal insulin analogues
Insulin glargine is a new long-acting basal insulin analogue (see Table 4.1 and Figure 4.1). It
is a soluble insulin which precipitates in situ after injection. It is important to note that insulin
glargine cannot be mixed with any other insulin. This modified insulin molecule has a stable
and smooth 24-hour profile.14 In a multicentre randomised study, insulin glargine was
compared with NPH insulin in children aged 5 to 16 on a basal-bolus regimen.15 The glargine
treated group had a greater reduction in fasting blood glucose levels, although overall HbA1c
improvement was similar in both groups. Glargine may decrease the risk of severe nocturnal
hypoglycaemia in children and adolescents.15-17 A recent Technology Appraisal Guidance
from the UK National Institute of Clinical Excellence concluded that insulin glargine should
be considered as a treatment option for people with type 1 diabetes.16
Insulin detemir is another basal insulin (see Table 4.1 and Figure 4.1). It is an acylated
insulin which binds to albumin. Preliminary studies in adults suggest that it has advantages
over isophane insulins when used in a basal/bolus regimen, with a significant reduction in
hypoglycaemia despite comparable HbA1c levels.18 A recent study of the pharmacokinetics of
insulin detemir showed no difference in serum concentration of insulin with time when
56
comparing children aged 6 to 12 years with adolescents aged 13-17 years and adults aged
over 18 years. There was less variability in response to insulin detemir compared with NPH.19
Premixed insulin preparations
Several premixed combinations of rapid-acting, short-acting and isophane insulins are
available in Australia with variable ratios available as detailed in Table 4.1.
In Australia, premixed insulin preparations are not generally recommended for first line
use in childhood and adolescent diabetes because of changing needs in the ratios of the two
insulins. Their use generally indicates a compromise; however the premixed combinations
may be helpful in some situations:
• When there are difficulties in accurately drawing up and mixing insulins.
• When ratios remain stable.
• When there are severe individual or family psychosocial problems disturbing diabetes
management.
• When adolescents are experiencing difficulty in complying with insulin regimens.
Typical action profiles of the various insulin preparations are illustrated in figure 4.1,
although there is much inter- and intra-individual variation.
Local Reactions to Insulin
Local reactions to insulin injections are uncommon, but when they do occur they are more
likely to be due to sensitivity to the added preservatives (metacresol, phenol or
methylhydroxybenzoate) than to the insulin itself.20;21 Two types of reaction have been
reported, a localised wheal and flare with itching due to histamine reactions, and generalised
anaphylaxis, which is extremely rare. A trial of insulin with a different preservative may
solve this problem. Formal identification of the preservative is possible using preservativeonly preparations available from the manufacturers. Antihistamine creams can also assist
with localised reactions. Cold-sensitivity urticaria should also be considered if the patient
develops a local reaction on using a vial directly from the refrigerator. Latex sensitivity (due
to transfer of latex particles from the septum of the insulin bottle) should also be
considered.22
Mixing Insulins
In order to maintain uniformity, short/rapid-acting insulin should be drawn up into the
syringe before the intermediate- or long-acting insulin. This strategy prevents contamination
of the short/rapid-acting insulin by the longer-acting insulin and eliminates the possibility of
converting the short/rapid-acting insulin into a longer-acting form.
Isophane insulin can be premixed with rapid-acting or short-acting insulin in the same
syringe or vial without altering the absorption profile of the rapid-acting or short-acting
insulin.23;24
Lente insulin can be safely given together with rapid-acting or short-acting insulins in the
same syringe providing the injection is administered immediately after mixing.25 Lente
insulin should never be premixed with rapid-acting or short-acting insulin and stored in the
same syringe or in a vial because of conversion of the short-acting insulin into a longer-acting
form.23
Isophane and lente insulins should never be mixed in the one syringe or vial.
Insulin glargine cannot be mixed with any other insulin.
57
Insulin Concentrations
One unit of insulin corresponds to approximately 36 micrograms or 6 nanomoles of insulin.
Australia and New Zealand have a single insulin concentration of 100 U/ml (U 100).
Insulins must be administered by insulin syringes calibrated to the concentration of the
insulin.
The availability of insulins of other concentrations (eg U 40) still exists in some countries
overseas. This is important information for Australian patients travelling internationally.
In very young children with very low insulin requirements, the insulin preparations may
need to be diluted in order to deliver doses accurate to 0.1 unit safely. The diluents are
obtained from the insulin manufacturers (the physician needs to obtain approval from the
Department of Health under the Special Access Scheme). The diluted preparations can be
stored for 3 months under refrigeration although the vial that is in use must be discarded after
1 month whether stored under refrigeration or at room temperature. When using diluted
insulins, special care must be taken to ensure that the correct dose is administered when using
standard insulin syringes. 25-unit syringes are extremely useful when small doses need to be
given.
Storage Conditions
The following storage conditions should be recognised:
• Insulin is stable at room temperature for several weeks providing there are no extremes
of temperature.
• Unused vials should be refrigerated (stored at 4 to 8°C) but never frozen.
• Insulin may lose its potency after opening the vial or when exposed to high
temperatures (eg in the tropics or if left in the car).
• Insulin vials should be discarded after 3 months of opening if kept refrigerated and after
1 month if kept at room temperature.
• Penfill cartridges and disposable insulin pens should be discarded after 21-28 days at
room temperature as per the manufacturer’s instructions for storage.
• The manufacturer’s expiry date should be adhered to.
Adjunct Therapy with Oral Antidiabetic Drugs
There is only limited experience of using metformin as an adjunct therapy to insulin in
children and adolescents with type 1 diabetes exhibiting insulin resistance. One randomised
controlled trial involving 27 adolescents with type 1 diabetes resulted in a decrease in HbA1c
of 0.6%, a slight decrease in insulin requirements, but also a slight increase in mild
hypoglycaemia.26 Another randomised controlled trial reported a decrease in HbA1c of 0.9%
over 3 months of metformin treatment however this change was not significant when the
changes in the pre- and post-test differences in HbA1c were re-calculated between the trial
arms .27 A non-randomised, uncontrolled study involving 10 adolescents and young adults
showed a decrease in HbA1c (for 7 of the 10 patients) after 6 months of metformin
treatment.28 This decrease did not reach statistical significance. After stopping metformin,
those who did respond to metformin showed a return of HbA1c to pre-treatment levels.28
58
Figure 4.1: Schematic Action Profiles of Insulin Preparations (profiles will vary with
dosage, injection site, depth of injection and other factors-see text)
59
Cost Issues
A recent Health Technology Appraisal assessed the clinical and cost-effectiveness of the
long-acting insulin analogue glargine in the management of diabetes.16 They found no
relevant economic evaluations in the medical literature. The manufacturer’s submission
included only 2 economic models relevant to type 1 diabetes, which the reviewers felt were
significant underestimates of the incremental cost effectiveness ratio (that is, insulin glargine
may be significantly less cost effective than is suggested by the manufacturer’s analysis).
However, on the balance of effectiveness and cost effectiveness evidence, the reviewers
concluded that insulin glargine could be considered as a treatment option in people with type
1 diabetes.16 This appraisal was conducted with the UK health system in mind and was not
specific to paediatrics, and, therefore, may not be generalisable to Australia.
The Evidence
The evidence comparing animal insulin with human insulin use in children and adolescents
with type 1 diabetes is listed in Evidence Table 4.1.
• A Cochrane Collaboration systematic review of 45 RCT’s (including 4 paediatric studies)
found no significant differences in metabolic control or hypoglycaemic episodes between
animal or human insulins.7(I)
The evidence on insulin glargine use in children and adolescents with type 1 diabetes is listed
in Evidence Table 4.2.
• A recent Technology Appraisal Guidance from the UK National Institute of Clinical
Excellence concluded that insulin glargine should be considered as a treatment option for
people with type 1 diabetes.16(I)
The evidence on metformin as an adjunct therapy to insulin in children and adolescents with
• There is only limited experience of metformin as an adjunct therapy to insulin in children
and adolescents with type 1 diabetes exhibiting insulin resistance One randomised
controlled trial involving 27 adolescents with type 1 diabetes resulted in a decrease in
HbA1c of 0.6% compared with placebo, a slight decrease in insulin requirements, but also
a slight increase in mild hypoglycaemia.26 Another randomised controlled trial showed a
non-significant decrease in HbA1c of 0.9% over 3 months of metformin treatment.27(II)
• A non-randomised, uncontrolled study involving 10 adolescents and young adults showed
a non statistically significant decrease in HbA1c (for 7 of the 10 patients) after 6 months of
metformin treatment.28(IV)
recommendations and principles of clinical practice are listed in Evidence Table 4.4.
• Health care professionals, parents and children and adolescents with type 1 diabetes
should be informed that insulin is essential for survival. There is no alternative to
treatment with insulin.1(T)
• Children and adolescents with type 1 diabetes should be treated with human insulin as
animal insulin has no advantage over human insulin in terms of metabolic control or
hypoglycaemia.7(I)
• A wide variety of human, analogue and bovine insulins are available in Australia for use
in children and adolescents with type 1 diabetes.29(C)
60
•
•
•
•
•
•
•
•
Rapid-acting insulin should be injected at the time of a meal and short-acting insulin
should be injected 15-20 minutes before a meal.13;30(C)
Rapid-acting insulin can be administered post-prandially in prepubertal children with type
1 diabetes with unpredictable eating habits (eg infants, toddlers and preschool
children).30(C)
Insulin glargine is a long-acting basal insulin analogue which has recently been introduced
as a treatment option.16(I)
To avoid confusion and prescribing errors, the use of the terms ‘clear’ to describe rapidacting or short-acting insulin and ‘cloudy’ to describe intermediate- or long-acting insulin,
should be discouraged as the long-acting analogues, glargine and detemir, are clear
solutions.
The action profile of the various insulin preparations is subject to inter- and intraindividual variation. The action profile is also affected by storage conditions and the
manufacturer’s storage instruction should be followed.30(C)
All children should have rapid/short-acting insulin available for sick-day
management.30;31(C)
Families need to ensure that a small supply of spare insulin is always available so that
supply is uninterrupted.31(C)
As there is limited and inconsistent evidence on the use and efficacy of metformin as an
adjunct therapy in type 1 diabetes, it should only be considered as an adjunct for difficult
to control patients with evidence of insulin resistance. Patients should be warned of and
closely monitored for hypoglycaemia during the stabilisation period and the efficacy
monitored.26;27;28(II)
I = Evidence from a systematic review of all relevant controlled trials
II = Evidence from at least one properly-designed RCT
T = WHO technical reports produced by expert panels
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Sarnblad S, Kroon M, Aman J: Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised
placebo-controlled trial with aspects on insulin sensitivity. European Journal of Endocrinology. 149:323-329, 2003
Gomez R, Mokhashi MH, Rao J, Vargas A, Compton T, McCarter R, Chalew SA: Metformin adjunctive therapy with insulin
improves glycemic control in patients with type 1 diabetes mellitus: a pilot study. Journal of Pediatric Endocrinology &
Metabolism 15:1147-1151, 2002
and Young People (DRAFT). 2004.
62
Chapter 5: Insulin Regimens and Delivery
The ultimate aim of insulin therapy is to provide physiological insulin replacement. However,
commonly used insulins and delivery methods have approximated this very poorly. The
availability of new (and future) insulin analogues and alternate delivery methods (eg insulin
pumps) offers the potential more closely to approximate normal physiology in suitable
subjects.
The choice of insulin types and regimen has to be guided by a variety of factors,1 including:
• Age of the patient.
• Lifestyle factors.
• Patient and family preferences and management skills.
• Metabolic targets.
• Duration of diabetes.
• Experience of the health care team.
• Affordability and sustainability.
• Associated complications, including hypoglycaemia.
Any insulin regimen has to be considered in the wider context of a total diabetes management
package, which must include dietary management, exercise, blood glucose monitoring, initial
and ongoing education, regular medical follow-up and psychological care. The use of terms
such as conventional insulin therapy and intensive insulin therapy is becoming blurred and
less useful as management options increase.
Insulin Regimens
The insulin regimen needs to aim to:
• Provide appropriate basal insulin requirements to cover the needs across 24 hours.
• Provide sufficient insulin levels when needed to cover food intake.
• Have adequate provision for adjustment and correction when needed.
• Minimise blood glucose fluctuation and risk of hypoglycaemia and hyperglycaemia.
• Achieve short-term and long-term metabolic targets.
Many regimens are in common use and there are many more that have had limited trials or
are in occasional use. The most commonly used regimens are listed and discussed below.
Children and adolescents will often evolve from one regimen to another in order to meet the
goals of therapy.
•
One injection daily:
Either intermediate-acting insulin or short/rapid-acting plus intermediate-acting insulin.
Such a regimen is rarely appropriate for children and adolescents with type 1 diabetes,
although is occasionally seen for short periods in those experiencing a profound remission
phase.
• Two injections daily:
A mixture of short/rapid-acting and intermediate-acting insulin given before breakfast and
before the main-evening meal. This can be custom mixed or supplied in a variety of premixed insulins. This regimen is commonly used in younger children.
63
•
Three injections per day:
A mixture of short/rapid-acting and intermediate-acting insulin given before breakfast,
short/rapid-acting insulin before the afternoon snack or main evening meal and
intermediate-acting insulin in the evening.
This regimen is commonly used in older children and teenagers when a 2 injection per
day regimen is inadequate.
• Four injections per day (basal-bolus regimen):
Short/rapid-acting insulin given before main meals, with intermediate-acting insulin given
in the evening or in the morning and evening, or with glargine given once daily (morning
or evening).
This regimen is used extensively in adolescents and adults with type 1 diabetes. There
are many variations of multiple injection regimens that are being tried.
• Insulin pump therapy (continuous subcutaneous insulin infusion – CSII)
The pump contains a rapid-acting insulin analogue only and is programmed to deliver
basal rates to match the individual’s needs. To cover meals and correct hyperglycaemia
bolus doses are activated by the patient. It should be noted that short-acting insulins are
not suitable for use in this regimen.
• Other less common regimens
Other insulin regimens may be suitable for some patients based on their individual
circumstances (eg 5 injections per day). Some of these are reported in the literature, but
will not be further discussed here.
In a recent audit in NSW of type 1 diabetes in the 0-15 years age group, 61.3% were
treated with 2 injections per day, 23.1% with three injections per day, 12.1% with four or
more injections daily, 3.2% with one injection and 0.2% with insulin pumps2 (it should be
noted that insulin pump programs have increased since this time). In an international multicentre audit, number of injections per day increased with age and duration of diabetes as
expected.3
Use of Short-Acting Insulin
In the above regimens, short-acting or rapid-acting insulins may be used. This is selected
according to the individual’s needs, especially considering food intake and energy
expenditure. The administration of rapid-acting analogues immediately before meals has been
considered to be preferable to patients and families and data suggest reductions in postprandial glucose rise.4,5 Insulin regimens using rapid-acting insulin analogues have been
shown to be associated with improved metabolic control compared to those using regular
insulin, however limited data in children has not confirmed this advantage.6 Patients using
rapid-acting analogues in physiological regimens overall have fewer hypoglycaemic episodes
than those using traditional insulins,7 however a review of studies in children including
physiological and non-physiological regimens did not show an overall difference between
rapid-acting analogues and short-acting insulin.62
In considering the timing of insulin injections, data are inconsistent on the optimal timing
of short-acting insulin in relation to meals, however pharmacokinetic data suggest that shortacting insulin should be given before meals and preferably up to 30 minutes prior.8;63 It is
recommended that rapid-acting insulins be given immediately prior to meals (within 15
minutes) to avoid hypoglycaemia.7 Giving rapid-acting insulin after meals has been shown to
be a useful option, particularly in infants and young children with unpredictable eating
patterns, allowing the dose to be judged after the amount of food ingested has been
observed.5
64
Use of Intermediate and Long-Acting Insulins
Intermediate-acting insulin is generally isophane insulin, however intermediate-acting lente
insulins are preferred by some, and some of the above regimens are also used with longacting insulins. It is likely that new long-acting insulin analogues will find a major role in
insulin regimens. One of the major limitations of regimens using conventional intermediateacting or long-acting insulins is the known intra-individual variation in absorption, which is
up to 45% in healthy subjects.9 These insulins are also problematical in that their peak of
action may not suit the individual and they have dose dependent pharmacokinetics - ie peak
effect and duration of effect vary with dose.
Insulin glargine is characterised by reproducibly flat basal profiles without significant dose
effects on pharmacokinetics and is the first long-acting analogue available in Australia. Adult
studies indicate similar HbA1c levels with insulin glargine but reduction in hypoglycaemia.10
There are insufficient data to draw conclusions on the efficacy of insulin glargine in children
and adolescents, although data to date suggests similar efficacy but less hypoglycaemia.11
Glargine seems most suited to use in basal-bolus regimens. However, trials are under way to
investigate its use as the evening long-acting insulin in twice daily regimens in children.12
Detemir insulin is another basal analogue under clinical trial. It is reported to have a more
reproducible profile of action compared to isophane insulins13 and preliminary studies
suggest reduction in hypoglycaemia with comparable HbA1c levels.14
Regimens using Pre-mixed Insulins
Studies have not demonstrated any difference in glycaemic control between pre-mixed or
custom-mixed insulin doses.15,16 Pre-mixed insulins are used in some centres for children on
twice-daily injections and also to have a simplified regimen when adherence difficulties are
present. They are usually used in pen devices. The potential disadvantage is that independent
adjustment of the component insulins is not possible, thereby reducing adjustment flexibility.
Number of Injections per Day
In adults with type 1 diabetes, it is clearly established that multiple injection regimens (basalbolus regimens) are superior to simpler injection regimens, preferably using rapid-acting
analogues as the bolus insulin.7 In adolescents in the DCCT, the intensively treated group
also had improved metabolic control and complication reduction, although this was part of a
broader intensive management package. Weight gain and hypoglycaemia rates were
increased in the intensively treated group. Most adolescents with type 1 diabetes should
receive intensive therapy aimed at achieving glycaemic control as close to normal as possible
to reduce the risk of microvascular complications.17,18
In the pre-adolescent age group, the superiority of multiple injection regimens has not
been clearly established and there continues to be wide differences in practice. It has been
common in children to use the simplest insulin regimen that achieves the goals of therapy and
thus many children are treated with 2 injections per day regimens. An additional rationale for
this approach is that most children enter a partial remission phase making achievement of
satisfactory glycaemia relatively easy during this time. However there are some paediatric
centres that advocate multiple injection regimens for all children and adolescents from the
start of therapy.19 A cross-sectional, multi-centre study of 2873 children and adolescents (age
range 1–18 years) from 18 countries demonstrated no effect of the number of insulin
injections per day on metabolic control.3 One large RCT (n=186, age 10-18 yrs) reported
improved metabolic control with a 3 injections per day regimen compared to 2 injections per
65
day.20 In a recent NSW audit including 1190 subjects, number of injections was not a
predictor of HbA1c, however multiple injections (more than 3 injections per day) was a
predictor of hypoglycaemia.2
Total Daily Insulin Dosage and Distribution
Insulin doses are tailored for each patient’s individual circumstances and requirements and
change often in children and adolescents. Factors affecting insulin doses are age, weight,
stage of puberty, duration of diabetes, food intake and distribution, exercise patterns, daily
routines, results of monitoring and intercurrent illness. As a general guide, total daily insulin
doses21 are as follows:
• Partial remission phase (any age): <0.5 unit/kg/day.
• Pre-adolescent children (beyond remission phase): 0.7 to 1 unit/kg/day.
• During puberty (beyond remission phase): 1.2-1.5 units/kg/day or higher.
The distribution of the total daily insulin dose varies greatly between individuals and requires
individual titration. Typical distributions are discussed.21
Twice daily insulin injection regimens: typically approximately 60-75% of the total daily
insulin dose is given in the morning and 25-40% at night with approximately 30% of each
dose being short-acting insulin.
Basal-bolus regimens: typically 40-60% of the total daily insulin dose is given as
intermediate acting or long-acting insulin before bed, with the remainder divided up into premeal boluses.
Insulin pump therapy: typically 45-60% (lower end of this range in young children and
higher end of this range often in adolescents) of the total daily insulin is given as basal insulin
and the remainder is provided by pre-meal boluses.22
Basal insulin requirements are usually considerably reduced (about 20%) when using
physiological regimens involving glargine or insulin pumps.7
Insulin Administration
Insulin absorption
The rate of absorption of insulin is affected by many factors as follows:
• Insulin type
• Injection site
Soluble insulin is absorbed more slowly and consistently from the subcutaneous site
compared to intramuscular injections.23 There is less difference with rapid-acting
analogues64. Thus subcutaneous injections are preferred. Insulin is also absorbed at
different rates from different anatomical locations.24 Absorption is quickest from the
abdomen, followed by the buttock and slowest from the thigh (non-exercising).
However, these differences are less pronounced with both rapid-acting and long-acting
analogues.65;66;67 Thus it is recommended that short/rapid-acting insulin or mixed doses
of insulin be injected in the abdomen. It is recommended that evening doses of
intermediate-acting insulin be given in the (non-exercising) thigh to optimise the
overnight profile of action.25 The upper arm is used by some for injections, however
this is not generally recommended in younger children because of the thin layer of
subcutaneous tissue at this site and the increased risk of intramuscular injection.
Rotation between different anatomical sites from day to day is not recommended
since this has been shown to be associated with higher and more variable blood glucose
levels.26
66
Figure 5.1: Recommended Injection Sites
•
Injection depth
Table 5.1: Mean Cutis/Subcutis Thickness
Mean cutis/subcutis thickness (mm) [measured by ultrasound without compression]
Site
Male Child
Female Child
Abdomen
9
15
- thigh anterolateral
10
14
- thigh anterior
10
13
Buttock
19
26
Adapted from Birkebaek NH, Johansen A, Solvig J. Diabetic Medicine 1998; 15(11):965-971.27
In assessing the suitability of different injection sites, studies have examined
subcutaneous tissue thickness and site of deposition of injections.27-29 There is a
significant risk of intramuscular injections (and hence more rapid absorption) which is
increased in lean individuals, especially boys. This can be minimised by using a two
finger pinch technique and an injection angle of 45 degrees. Shorter needles reduce the
risk of intramuscular injections.30 In general most children and adolescents should use 8
mm needles with a pinch-technique and 45 degree angle, and if lean and using pens, 5
or 6 mm needles may be appropriate.
Intramuscular injection of insulin can increase absorption from the thigh by up to
50%, but it has been reported that there is no difference between subcutaneous and
intramuscular absorption from the abdomen.31
• Insulin dose
Insulin has dose-dependent absorption kinetics. Small doses are absorbed more quickly
than large doses.32
•
Temperature
67
Insulin absorption is increased with increased ambient and body temperature, related to
increased subcutaneous blood flow.32 Therefore care should be taken in hot weather and
warm baths/saunas after insulin injections.
• Exercise
Exercise increases insulin absorption, again predominantly related to increased
subcutaneous blood flow. For this reason the thigh is not recommended prior to
exercise.32
• Age of child and fat mass
Large fat mass is associated with increased subcutaneous tissue thickness and therefore
slower absorption. Since younger children are often leaner, insulin absorption is often
faster.
• Presence of lipohypertrophy or lipoatrophy
Adverse changes at the injection site can considerably affect absorption.
Lipohypertrophy is a common problem in diabetes management and absorption of
insulin from these sites is delayed and erratic.33 This can be avoided by moving the
injection site from day to day within the same anatomical area of the body, or
periodically moving to another anatomical site. Prevalence of lipohypertrophy has been
estimated at 20-30% in patients with type 1 diabetes.34 Other factors associated with
risk of lipohypertrophy are presence of insulin antibodies.
Lipoatrophy is now much less common with modern pure insulins. However, it still
occurs in a small number of subjects and also leads to erratic insulin absorption.35 An
immunological basis has been suggested, including sensitivity to components of the
insulin preparation or latex.
Insulin Delivery Devices
Insulin syringes and pens
Insulin syringes are disposable plastic syringes, designed for single use only and are available
in a range of sizes (25, 50 and 100 units) and needles lengths (8 mm, 12 mm and 12.7 mm).
The lowest volume syringe that will hold the required dose should be used to increase
accuracy of dose. It is common for children receiving mixed injections of insulin to have
these drawn up into the same syringe to reduce the number of injections. Not all insulin types
are compatible for mixing - (see chapter 4). U100 insulin is exclusively used in Australia,
although occasionally dilution is performed for babies or infants requiring very small doses.
Insulin pens are also available which contain pre-filled cartridges of insulin. Cartridges are
available for the rapid-acting analogues, short-acting and isophane insulins but not for lente
and ultralente insulins which are not stable in pen systems. Needle lengths available are 5, 6,
8, 12 and 12.7 mm. Families should know how to use an insulin syringe even if the delivery
device is primarily a pen in case of unexpected failure of the pen. Disposable pens are also
available for some insulin types which gives added convenience of being able to have pens
stored in various locations. Increased satisfaction with pens has been shown in some
studies.36 Side-effects are not different between syringe or pen delivery.
The accuracy of pen versus syringe delivery has been studied. In one study,37 attempting a
dose of 1 unit of insulin was found on average to deliver a mean of 0.89 units with a pen and
1.23 units with an insulin syringe (small but significant differences). Another study found
pens more accurate than syringes for doses less than 5 units,38 but no differences for larger
doses. Available pens generally are adjustable in 1 unit increments, although one pen is
available that can be adjusted in 0.5 unit dose increments.
68
Automatic injection devices
Devices that automatically insert the needle into the skin are available for attachment to some
pens or for syringes. These may be preferred by some patients who find it difficult to insert
the needle through the skin and also because the needle is hidden until the device is activated.
Reduced pain perception has been reported with the use of an automatic injection device.68
Jet injection devices
A jet injector uses high pressure to form a thin stream of insulin that penetrates the skin.
Metabolic control has been reported to be similar in the short-term but patient acceptance is
less than for needle injections39 and higher adverse event rates are reported.40 Jet injectors
may have an occasional role for extreme needle phobia.
Indwelling cannulas
Indwelling subcutaneous cannulas are in use in some centres as an alternative to repeated
needle injections to reduce injection pain, especially at the onset of diabetes.69 Cannulas are
usually replaced very 4 to 5 days. Insulin absorption and metabolic control has been reported
to be unchanged,41,42 making this a possible option if preferred by the patient.
Insulin pumps (CSII)
Insulin pumps have been proposed as offering more physiological insulin delivery and
therefore advantages in metabolic control, reduction in hypoglycaemia and improvement in
lifestyle flexibility and patient acceptability (see also insulin pump adjustments).
A meta-analysis of 12 RCT’s, mainly in adults but with some adolescents, reported that
pump patients had lower mean BG level by 1.0mmo/L, lower HbA1c by 0.51% and lower
insulin requirements by 14% compared to patients on optimised insulin injections.43 In
another meta-analysis including 52 studies with 1547 adult, adolescent and paediatric
subjects, improvement in glycaemic control was also reported.44 Overall, hypoglycaemia is
markedly less frequent with pumps than in intensive injection regimens.45 It has been
suggested that pump therapy increases the risk of diabetic ketoacidosis, but this may only be
with pumps used prior to 1993.
There are limited RCT’s in adolescents and none exist for children. Observational studies
have reported significant improvements in HbA1c, reduction in hypoglycaemia and higher
satisfaction,46-48 but not in all studies. A NICE technical appraisal recommended that insulin
pump therapy should be available as an option for people with type 1 diabetes who have
failed multiple-dose insulin therapy (HbA1c >7.5% or >6.5% in the presence of
complications, or disabling hypoglycaemia).49 Full economic analysis that takes into account
possible long-term reduction in morbidity and mortality has not been possible. However,
insulin pump therapy costs more than injection therapy in the short-term.
Management with insulin pump therapy is increasing in Australia, however not all patients
are suitable and individual units should have suitability assessment criteria. Accessibility to
this therapy is also currently significantly limited by financial costs. Additional training and
expertise for health care professionals is required for units initiating and maintaining insulin
pump therapy.
Practical Aspects of Insulin Administration
Disinfection of the skin is not necessary prior to insulin injections. However, injections
should be given through clean, healthy skin.7 Some patients inject through clothing at times
for reasons of convenience and no significant problems have been reported with this
practice.50
69
The age at which children can reliably draw up and administer an insulin injection or use
an insulin pen varies markedly between children.70 Many children assist in the insulin
injection routine from 9-10 years of age and many can easily use an insulin pen from that age.
Drawing up of two different insulin types into a syringe requires more concentration and
dexterity and is often not appropriately mastered until sometime after 10 years of age.
Appropriate supervision by carers is recommended to avoid insulin dose errors or omissions
which have not been quantified, but practical experience suggests that these are common.
While insulin syringes and needles are recommended for single use only, surveys indicate
that some patients re-use syringes and needles and that this is not associated with increased
infections or other adverse events.
Insulin syringes and pen needles need to be disposed of in a safe and hygienic way.
Needles should not be recapped to avoid the risk of needle-stick injury. Approved sharps
containers should be provided and disposed of according to local authority regulations.
Unfortunately there are not yet uniform or appropriate arrangements for sharps disposal in all
areas of Australia.
Thorough re-suspension of intermediate-acting and long acting insulins that are in
suspension (all currently available types, except glargine) is critical to avoid dosage error and
variation and many patients re-suspend inadequately.51 Pens containing isophane need to be
tipped at least 20 times for adequate mixing.
Insulin Adjustment
Appropriate adjustment of insulin doses is critical if goals of diabetes therapy are to be
achieved. This is particularly important in children and adolescents in whom insulin
requirements can change rapidly with growth and puberty and changes are also needed to
cope with variations in activity and food intake and intercurrent illness. However insulin
adjustment is a skill that is often not well mastered by patients and families with diabetes.52
Insulin adjustment by a diabetes nurse educator has been shown to improve glucose control53
and strategies employing electronic transmission of glucose monitoring to a diabetes centre
for advice have been reported to be successful.54
Children and their families need to acquire skills in the following areas of insulin
adjustment:55
Adjusting usual doses of insulin based on blood glucose patterns over several days or
longer
Patients on insulin injection therapy are advised to make adjustments to the appropriate dose
in approximately 10% increments and observe the effects of this over several days before
making further changes. Half unit increments can be made in patients on small doses (<5
units). Patients on insulin pump therapy need to evaluate whether changes need to be made in
basal or bolus doses from their monitoring and basal rate tests; incremental changes of 5-10%
are also appropriate. More rapid changes may be appropriate in some circumstances eg severe
hypoglycaemia.
The routine use of sliding scales for daily insulin adjustment has not been systematically
studied. However, it is generally not recommended as a primary tool for insulin adjustment
because of its retrospective nature. Used in in-patients, sliding scales have been shown to be
inferior to alternative management strategies.56;57
70
Pro-active day to day adjustments to insulin based on activity and food intake
These adjustments should be pro-active and, as far as possible, take into account activity
levels and meals during the period of action of the dose. Larger short-term adjustments can
sometimes be needed eg up to 50% reductions for vigorous or prolonged exercise.
Adjustments to correct the current BG level when it is outside the desired range
Patients and families should have skills to correct high BG levels when these are not
transient. Recommendations are usually to give an additional short/rapid-acting insulin dose
of between 5% and 10% of the total daily insulin dose to correct high BG levels without
significant ketones. However, higher doses may be required for ketosis and sick days (see
chapter 11). Formulas are also available to guide correction doses and these are often used by
patients on insulin pumps.22 Patients who give additional corrective doses when needed
between usual doses have been shown to have improved metabolic control.58
Insulin pump adjustments
Insulin pump therapy should be initiated and supervised by a specialised multi-disciplinary
team trained in pump therapy in children and adolescents with diabetes.
Rapid-acting insulin analogues are recommended for pump use. As a guide, patients
starting on insulin pump therapy have the previous total daily dose on injections reduced by
approximately 25%. The pump is initially programmed to deliver 45-60% of the new total
daily dose as the basal insulin. Often, a single hourly basal rate is used over the 24 hours and
this is subsequently modified on the basis of blood glucose monitoring. Adjustments to
hourly rates are usually no more than 10% at a time. Most pump users have 2-5 different
basal rates for different periods of the day. For example, it is common for people to need a
little less basal insulin in the late evening (between 8pm and 2 am) and during the day when
more active (between 10 am and 4 pm). Slightly higher basal rates are often needed in the
early evening (from 4 pm to 8 pm) and morning hours (from 2 am to 10 am) because of the
tendency of the blood glucose to rise toward morning (the dawn phenomenon). Many
prepubertal children need a higher basal rate late in the evening (9 pm to 12 midnight).71
Bolus doses are needed for meals and for correction of hyperglycaemia. A useful guide to
estimate bolus doses for meals is to employ the ‘500’ rule (the total daily dose is divided into
500 to estimate the number of gm of carbohydrate that 1 unit of insulin will cover).72 This is
then used to derive a more practical figure of how many units of insulin are needed to cover
each 15 gm exchange of carbohydrate in each meal or snack (for a patient on 50 units of
insulin per day, a 1.5 unit bolus would be needed for each 15 gm exchange of carbohydrate).
It is recommended that calculations be made at least to the half exchange, and some advocate
calculations to the gram if practical.
Correction boluses to correct hyperglycaemia can be given at any time or added to meal
boluses. A useful guide to estimate correction doses is to employ the ‘100’ rule (the total
daily dose is divided into 100 to estimate the number of mmol/L that the blood glucose will
fall by giving 1 unit of insulin).72 For example, for a patient on 50 units of insulin per day, the
blood glucose should fall by approximately 2 mmol/L for each additional 1 unit of insulin.
This calculation can also be used to estimate a negative correction to correct for
hypoglycaemia (in a patient on 50 units of insulin a day, giving 1 unit less at meal times
should allow the blood glucose to rise by 2 mmol/L).
Correction doses given for hyperglycaemia should take into consideration the residual
effect of any previous meal or correction bolus dose. A useful guide is to use the ‘unused
bolus rule’ (approximately 30% of a rapid-acting insulin bolus is absorbed each hour). The
correction dose should be reduced accordingly. For example, if 5 units had been given as a
meal bolus 2 hours previously, 60% would have been absorbed and the remaining 40% or 2
71
units would still be exerting an effect. This should be subtracted from any correction dose.
The pump should not be used to correct hyperglycaemia when ketones are present - control
should be regained with an insulin injection via pen or syringe (see chapter 11).
Basal rates, meal bolus doses and correction bolus doses calculated by the above methods
are a starting point. Fine-tuning adjustments are then made on the basis of blood glucose
response and patterns. Adjustment of basal rates is assisted by doing basal rate tests, which
involve testing different periods of the day by omitting or having a carbohydrate-free main
meal and snack and monitoring blood glucose frequently during that period - if the basal rate
is appropriate, the blood glucose should remain steady or rise or fall only minimally during
that time.
Pumps are becoming available that assist the user in making many of the adjustment
calculations.
Cost Issues
A recent Health Technology Assessment attempted to establish the cost effectiveness of
Continuous Subcutaneous Insulin Infusion versus Multiple Daily Injections.59 The results
were inconclusive due to the paucity of reliable information about cost effectiveness derived
from the formal clinical evidence.59 Another cost effectiveness analysis using a Markov
model concluded that Continuous Subcutaneous Insulin Infusion was most cost effective in
patients who required more frequent admission to hospital and had more frequent severe
hypoglycaemic events.60 Both studies were based on the UK health system and may not be
generalisable to the Australian health care system.
The Evidence
The evidence relating to the number of daily injections to diabetes control is listed in
Evidence Table 5.1.
• In adolescents in the DCCT, the intensively treated group had improved metabolic control
and complication reduction, although this was part of a broader intensive management
package.17;18(II)
• A cross-sectional, multi-centre study of 2873 children and adolescents (age range 1-18
years) from 18 countries demonstrated no effect of the number of insulin injections per
day on metabolic control.3(IV)
• One large RCT (n=186, age 10-18 yrs) reported improved metabolic control with a 3
injections per day regimen compared to 2 injections per day.20(II)
• A NSW audit including 1190 subjects, number of injections was not a predictor of HbA1c,
however multiple injections (more than 3 injections per day) was a predictor of
hypoglycaemia.2(IV)
The evidence on the length of needle for the injection for insulin therapy in the treatment of
children with type 1 diabetes is contained in Evidence Table 5.2.
• A randomised controlled trial in 50 children with type 1 diabetes demonstrated that using
shorter needles (8 mm compared to 12.7 mm) resulted in significantly fewer accidental
intramuscular injections of insulin.30(II)
The evidence on whether children and adolescents with type 1 diabetes should be treated with
insulin pump therapy is contained in Evidence Table 5.3.
• A meta-analysis of 12 RCT’s mainly in adults but with some adolescents reported that
pump patients had lower mean BG level by 1.0 mmol/L, lower HbA1c by 0.51% and lower
insulin requirements by 14% compared to patients on optimised insulin injection.43(I)
72
•
In another meta-analysis including 52 studies with 1547 adult, adolescent and paediatric
subjects on insulin pumps, improvement in glycaemic control was also reported.44(I)
• This meta-analysis found that hypoglycaemic episodes are less frequent with pumps than
in intensive injection regimens.44(I)
• A National Institute of Clinical Excellence (NICE) Technology Appraisal Report from the
UK referred to in Evidence Table 5.3 recommended that insulin pump therapy should be
available as an option for people with type 1 diabetes who have failed multiple-dose
insulin therapy (HbA1c >7.5% or >6.5% in the presence of complications, or disabling
hypoglycaemia).49(T)
2;3;20
• There is a variable effect of the number of daily injections on metabolic control.
(II, IV)
• Intensive management (including multiple daily injections or pump therapy, education,
intensive monitoring and psychosocial support) of type 1 diabetes in adolescents improves
metabolic control and reduces the risk of microvascular complications.17;18(II)
• Many insulin regimens are used in the treatment of type 1 diabetes in children and
adolescents. Any insulin regimen has to be considered in the wider context of a total
diabetes management package, which must include dietary management, exercise and
physical activity, blood glucose monitoring, initial and ongoing education, regular medical
follow-up and psychological care.1;61(C)
• Insulin doses should be tailored for each patient’s individual circumstances and
requirements, taking into account age, weight, stage of puberty, duration of diabetes, food
intake and distribution, exercise patterns, daily routines, results of monitoring and
intercurrent illness.1;61(C)
• It is recommended that insulin be injected in the abdomen, buttock or non-exercising
thighs. The upper arm is generally not recommended because of the thin layer of
subcutaneous tissue at this site and the increased risk of intramuscular injection.1;61(C)
• There is a significant risk of accidental intramuscular injections (and hence more rapid
absorption) especially in lean individuals. This can be minimised by using a two finger
pinch technique, an injection angle of 45 degrees and 8 mm needles.30(II)
55;62
• 5 or 6 mm needles may be appropriate in lean children or those using pens.
(C)
43;44;49
• Insulin pumps should be considered as a treatment option.
(I)
• Insulin pump therapy should be initiated and supervised by a specialised multi-disciplinary
team trained in pump therapy in children and adolescents with diabetes.49(C)
• Insulin syringes and pen needles need to be disposed of in a safe and hygienic way.
Needles should not be recapped to avoid the risk of needle-stick injury. Approved sharps
containers should be provided and disposed of according to local authority
regulations.55(C)
• Health care professionals should educate and encourage children and their families to
acquire skills in insulin adjustment.55(C)
I = Evidence from a systematic review of all relevant controlled trials
Reference List
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73
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3.
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8.
9.
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22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
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37.
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children and adolescents with type 1 diabetes from NSW and the ACT. Medical Journal of Australia 177(5):235-238., 2002
Mortensen HB, Hougaard P. Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with
IDDM from 18 countries. The Hvidore Study Group on Childhood Diabetes. Diabetes Care 20(5):714-720, 1997
Fairchild JM, Ambler GR, Genoud-Lawton C, Westman EA, Chan A, Howard NJ et al. Insulin Lispro versus regular insulin in
children with type I diabetes on twice daily insulin. Pediatric Diabetes 1:135-141, 2000
Schernthaner G, Wein W, Sandholzer K, Equiluz-Bruck S, Bates PC, Birkett MA. Postprandial insulin lispro. A new therapeutic
option for type 1 diabetic patients. Diabetes Care 21(4):570-573, 1998
Deeb LC, Holcombe JH, Brunelle R, Zalani S, Brink S, Jenner M et al. Insulin lispro lowers postprandial glucose in prepubertal
children with diabetes. Pediatrics 108(5):1175-1179, 2001
DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. Journal of the American
Medical Association 289(17):2254-2264, 2003
Insulin administration. Diabetes Care 26 Suppl 1:S121-S124, 2003
Owens DR, Zinman B, Bolli GB. Insulins today and beyond. Lancet 358(9283):739-746, 2001
Ratner RE, Hirsch IB, Neifing JL, Garg SK, Mecca TE, Wilson CA. Less hypoglycemia with insulin glargine in intensive insulin
therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes. Diabetes Care 23(5):639-643., 2000
Murphy NP, Keane SM, Ong KK, Ford-Adams M, Edge JA, Acerini CL et al. Randomized cross-over trial of insulin glargine plus
lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens. Diabetes Care
26(3):799-804, 2003
Dixon BF, Chase P, Fiallo-Scharer RH, Walravens PA, Klingensmith GA, Rewere MJ et al. The addition of insulin glargine to
lower hypoglycemic events and A1c levels in children and adolescents with type 1 diabetes. American Diabetes Association 63rd
Scientific Sessions 2003.
Danne T, Lupke K, Walte K, Von Schuetz W, Gall MA. Insulin detemir is characterized by a consistent pharmacokinetic profile
across age-groups in children, adolescents, and adults with type 1 diabetes. Diabetes Care 26(11):3087-3092, 2003
Vague P, Selam JL, Skeie S, De L, I, Elte JW, Haahr H et al. Insulin detemir is associated with more predictable glycemic control
and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin
aspart. Diabetes Care 26(3):590-596, 2003
Arslanoglu I, Saka N, Bundak R, Gunoz H, Darendeliler F. A comparison of the use of premixed insulins in pen-injectors with
conventional patient-mixed insulin treatment in children and adolescents with IDDM. Is there a decreased risk of night
hypoglycemia? Journal of Pediatric Endocrinology & Metabolism 13(3):313-318, 2000
Mastrototaro JJ, Gross TM. Reproducibility of the continuous glucose monitoring system matches previous reports and the
intended use of the product. Diabetes Care 26(1):256-257, 2003
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development
and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine 329(14):977986, 1993
White NH, Cleary PA, Dahms W, Goldstein D, Malone J, Tamborlane WV. Beneficial effects of intensive therapy of diabetes
139(6):804-812, 2001
Ludvigsson J, Bolli GB. Intensive insulin treatment in diabetic children. Diabetes, Nutrition & Metabolism 14(5):292-304, 2001
Bougneres PF, Landais P, Mairesse AM, Jais JP, Jos J, Peyraud J et al. Improvement of diabetic control and acceptability of a
three-injection insulin regimen in diabetic adolescents. A multicenter controlled study. Diabetes Care 16(1):94-102, 1993
Wolfsdorf JI, Anderson BJ, Pasquarello C. Treatment of the child with diabetes. In: Joslin's Diabetes Mellitus. Editors: Kahn CR,
Weir GC, 530-551, 1994
Walsh J, Roberts R. Pumping insulin. Everything you need for success with an insulin pump. San Diego: Torry Pines Press, 2002.
Vaag A, Pedersen KD, Lauritzen M, Hildebrandt P, Beck-Nielsen H. Intramuscular versus subcutaneous injection of unmodified
insulin: consequences for blood glucose control in patients with type 1 diabetes mellitus. Diabetic Medicine 7(4):335-342, 1990
Koivisto VA, Felig P. Alterations in insulin absorption and in blood glucose control associated with varying insulin injection sites
in diabetic patients. Annals of Internal Medicine 92(1):59-61, 1980
Henriksen JE, Vaag A, Hansen IR, Lauritzen M, Djurhuus MS, Beck-Nielsen H. Absorption of NPH (isophane) insulin in resting
diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site. Diabetic Medicine 8(5):453-457, 1991
Bantle JP, Weber MS, Rao SM, Chattopadhyay MK, Robertson RP. Rotation of the anatomic regions used for insulin injections
and day-to-day variability of plasma glucose in type I diabetic subjects. Journal of American Medical Association 263(13):18021806, 1990
Birkebaek NH, Johansen A, Solvig J. Cutis/subcutis thickness at insulin injection sites and localization of simulated insulin boluses
in children with type 1 diabetes mellitus: need for individualization of injection technique? Diabetic Medicine 15(11):965-971,
1998
Frid A, Linden B. Where do lean diabetics inject their insulin? A study using computed tomography. British Medical Journal
(Clinical Research Edition) 292(6536):1638, 1986
Smith CP, Sargent MA, Wilson BP, Price DA. Subcutaneous or intramuscular insulin injections. Archives of Disease in Childhood
66(7):879-882, 1991
Tubiana-Rufi N, Belarbi N, Du Pasquier-Fediaevsky L, Polak M, Kakou B, Leridon L et al. Short needles (8 mm) reduce the risk of
intramuscular injections in children with type 1 diabetes. Diabetes Care 22(10):1621-1625, 1999
Frid A, Gunnarsson R, Guntner P, Linde B. Effects of accidental intramuscular injection on insulin absorption in IDDM. Diabetes
Care 11(1):41-45, 1988
Binder C, Lauritzen T, Faber O, Pramming S. Insulin pharmacokinetics. Diabetes Care 7(2):188-199, 1984
Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care
7(5):479-480, 1984
Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors.
Experimental Clinical Endocrinology & Diabetes 104(2):106-110, 1996
Richardson T, Kerr D. Skin-related complications of insulin therapy: epidemiology and emerging management strategies. American
Journal of Clinical Dermatology 4(10):661-667, 2003
Cefalu WT. Evaluation of alternative strategies for optimizing glycemia: progress to date. American Journal of Medicine 113 Suppl
6A:23S-35S, 2002
Gnanalingham MG, Newland P, Smith CP. Accuracy and reproducibility of low dose insulin administration using pen-injectors and
syringes. Archives of Disease in Childhood 79(1):59-62, 1998
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38. Lteif AN, Schwenk WF. Accuracy of pen injectors versus insulin syringes in children with type 1 diabetes. Diabetes Care
22(1):137-140, 1999
39. Houtzagers CM, Visser AP, Berntzen PA, Heine RJ, van der Veen EA. The Medi-Jector II: efficacy and acceptability in insulindependent diabetic patients with and without needle phobia. Diabetic Medicine 5(2):135-138, 1988
40. Theintz GE, Sizonenko PC. Risks of jet injection of insulin in children. European Journal of Pediatrics 150(8):554-556, 1991
41. Hanas SR, Carlsson S, Frid A, Ludvigsson J. Unchanged insulin absorption after 4 days' use of subcutaneous indwelling catheters
for insulin injections. Diabetes Care 20(4):487-490.,1997
42. Hanas SR, Ludvigsson J. Metabolic control is not altered when using indwelling catheters for insulin injections. Diabetes Care
17(7):716-718, 1994
43. Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin
injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. British Medical Journal 324(7339):705,
2002
44. Weissberg-Benchell J, Antisdel-Lomaglio J, Seshadri R. Insulin pump therapy: a meta-analysis. Diabetes Care 26(4):1079-1087,
2003
45. Pickup J, Keen H. Continuous subcutaneous insulin infusion at 25 years: evidence base for the expanding use of insulin pump
therapy in type 1 diabetes. Diabetes Care 25(3):593-598, 2002
46. Boland EA, Grey M, Oesterle A, Fredrickson L, Tamborlane WV. Continuous subcutaneous insulin infusion. A new way to lower
risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes. Diabetes Care
22(11):1779-1784, 1999
47. Litton J, Rice A, Friedman N, Oden J, Lee MM, Freemark M. Insulin pump therapy in toddlers and preschool children with type 1
diabetes mellitus. Journal of Pediatrics 141(4):490-495, 2002
48. Plotnick LP, Clark LM, Brancati FL, Erlinger T. Safety and effectiveness of insulin pump therapy in children and adolescents with
type 1 diabetes. Diabetes Care 26(4):1142-1146, 2003
49. National Institute for Clinical Excellence (NICE). Guidance on the use of subcutaneous insulin infusion for diabetes. 1-23. 2003.
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51. Jehle PM, Micheler C, Jehle DR, Breitig D, Boehm BO. Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in
pens. Lancet 354(9190):1604-1607, 1999
52. Bonnet C, Gagnayre R, d'Ivernois JF. Learning difficulties of diabetic patients: a survey of educators. Patient Education and
Counseling 35(2):139-147, 1998
53. Thompson DM, Kozak SE, Sheps S. Insulin adjustment by a diabetes nurse educator improves glucose control in insulin-requiring
diabetic patients: a randomized trial. Canadian Medical Association Journal 161(8):959-962, 1999
54. Biermann E, Dietrich W, Standl E. Telecare of diabetic patients with intensified insulin therapy. A randomized clinical trial. Study
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56. Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus.
Annuls of Internal Medicine 157(5):545-552, 1997
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prospective regimens. Family Practice Research Journal 14(4):313-322, 1994
58. Denker PS, Leonard DR, DiMarco PE, Maleski PA. An easy sliding scale formula. Diabetes Care 18(2):278, 1995
59. UK NHS National Coordinating Centre for Health Technology Assessment (NCCHTA). The clinical effectiveness and cost
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60. Scuffham P, Carr L: The cost-effectiveness of continuous subcutaneous insulin infusion compared with multiple daily injections for
the management of diabetes. Diabetic Medicine 20:586-593, 2003.
62. National Institute for Clinical Excellence. Type 1 Diabetes (Childhood): Diagnosis and Management of Type 1 Diabetes in
Children and Young People. 2004
63. Sackey AH, Jefferson IG: Interval between insulin injection and breakfast in diabetes. Archives of Disease in Childhood. 71:248250, 1994
64. Rave K, Heise T, Weyer C, Herrnberger J, Bender R, Hirschberger S, Heinemann L: Intramuscular versus subcutaneous injection
of soluble and lispro insulin: comparison of metabolic effects in healthy subjects. Diabetic Medicine. 15:747-751, 1998
65. ter Braak EW, Woodworth JR, Bianchi R, Cerimele B, Erkelens DW, Thijssen JH, Kurtz D: Injection site effects on the
pharmacokinetics and glucodynamics of insulin lispro and regular insulin. Diabetes Care. 19:1437-1440, 1996
66. Mudaliar SR, Lindberg FA, Joyce M, Beerdsen P, Strange P, Lin A, Henry RR: Insulin aspart (B28 asp-insulin): a fast-acting
analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic
subjects. Diabetes Care. 22:1501-1506, 1999
67. Owens DR, Coates PA, Luzio SD, Tinbergen JP, Kurzhals R: Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in
healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites. Diabetes Care. 23:813-819,
2000
68. Diglas J, Feinbock C, Winkler F, Egger T, Weitgasser R, Pieber T, Lytzen L, Irsigler K: Reduced pain perception with Pen
Mate(TM), an automatic needle insertion device for use with an insulin pen. Practical Diabetes International 16:39-41, 1999
69. Hanas R: Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety. Journal of
Pediatrics 140:315-320, 2002
70. Wysocki T, Meinhold PM, Taylor A, Hough BS, Barnard MU, Clarke WL, Bellando BJ, Bourgeois MJ: Psychometric properties
and normative data for the parent version of the diabetes independence survey. Diabetes Educator 22:587-591, 1996
71. Conrad SC, McGrath MT, Gitelman SE: Transition from multiple daily injections to continuous subcutaneous insulin infusion in
type 1 diabetes mellitus. Journal of Pediatrics. 140:235-240, 2002
72. Walsh J and Roberts R: Pumping insulin. Everything you need for success with an insulin pump. Torrey Pines, 2000
75
Chapter 6: Glycaemic Control
Intensive Diabetes Management
The Diabetes Control and Complications Trial (DCCT) confirmed the benefit of maintaining
near normoglycaemia in reducing the development and progression of diabetic microvascular
complications in adolescents and adults.1;2 Even in patients with the same HbA1c intensive
therapy was superior to conventional.3 In the DCCT there was no lower threshold of HbA1c
below which the risk of complications was eliminated, and any improvement in HbA1c
conferred a reduction in risk.3;4 Longer follow up of patients after the completion of the
DCCT, in the EDIC (Epidemiology of Diabetes Interventions and Complications) study
showed increasing reduction of microvascular and macrovascular complications with optimal
early metabolic control.5;6
Achieving excellent glycaemic control is more difficult in children and adolescents than in
many adults because of the following factors:
• Insulin deficiency is often more complete.
• Variable food intake.
• Recurrent infections during childhood.
• Variable exercise patterns.
• Varying rates of growth and development.
• Hormonal changes, including insulin resistance during puberty, necessitating high and
changing insulin requirements.
• Behavioural problems associated with psychosocial difficulties.
• Conflict between being dependent upon parental involvement and wish for increased
independence during adolescence.
• Difficulty with adherence to diabetes regimens, particularly during adolescence when
insulin omission and infrequent blood glucose monitoring is common (thereby
preventing the benefits of more intensive insulin regimens).
Risks and Side Effects of Intensive Diabetes Management
Long-term benefits of intensifying management need to be weighed against the risks of:
2
• Increased frequency and severity of hypoglycaemia.
In a longitudinal Australian study, severe hypoglycaemia was associated with lower
verbal and full-scale intelligence quotient scores. Attention, processing speed, and
executive skills were particularly affected in children with younger onset of
diabetes.7
2
• Weight gain.
• Increased risk of precipitating rebellion and rejection of diabetes routines altogether.
Indicators of Poor Glycaemic Control
The indicators of poor glycaemic control may include the following clinical and biochemical
features:
• Polyuria and polydipsia.
• Enuresis and nocturia.
• Blurred vision.
• Weight loss or failure to gain weight with growth.
• Poor growth.
76
•
•
•
•
•
•
Pubertal delay.
Skin infections (staphylococcal and candidal).
Deteriorating school performance and absenteeism.
Signs of diabetes complications.
Elevated HbA1c and fructosamine.
Elevated blood lipids.
Glycaemic Goals
The National Institute of Clinical Excellence Guideline ‘Type 1 Diabetes (Childhood):
Diagnosis and Management of Type 1 Diabetes in Primary and Secondary Care’ makes the
following recommendation: Children with type 1 diabetes and their parents should be
informed that the optimal target for long-term glycaemic control is an HbA1c level of less
than 7.5% without an increase in hypoglycaemia.
In England an audit of children (0-16years) with type 1 diabetes found that in all age
groups fewer than 20% of children managed to achieve a HbA1c level of 7.5% or below.8
In 1999 in NSW, fewer than 25% of children and adolescents had a HbA1c levels <7.5%,
with the median HbA1c being 8.2% [interquartile range 7.6-9.1%].9;10
In order to achieve an HbA1c <7.5%, everyday blood glucose targets (ie. glycaemic goals)
need to be defined and while they still need to be individualised reasonable values to aim for
are:
11
• A pre-prandial blood glucose level of 4-8 mmol/L.
11
• A post-prandial blood glucose level of less than 10 mmol/L.
In very young children, in whom there is the greatest concern about the effects of
hypoglycaemia on the developing brain, glycaemic targets need to be at the upper part of
these ranges or a little higher.
Glycaemic targets need to take into account such additional factors as:
• Hypoglycaemia unawareness.
• Unpredictability of hypoglycaemia in some children.
• Past history of recurrent severe hypoglycaemia.
• Ability to comply with blood glucose monitoring.
• Presence of psychological or psychiatric disturbances.
• Presence of any coexisting disease which may affect the diabetes (eg infections).
• Presence of any coexisting disease (eg epilepsy).
Realistic goals for individual patients have to be reassessed at each visit. Appropriate
therapeutic strategies to reach the goals have to be clearly formulated, taking into
consideration the psychosocial and developmental aspects of the child and family.
Patients during the pubertal phase may have particular difficulties in maintaining good
control due to physiological and psychological changes, and therefore frequently require
special counselling services and support.
While blood glucose testing provides much data on glycaemic control, it also has placed a
very great burden on the child, adolescent and family in the quest for achieving optimal blood
glucose levels. Health care professionals must avoid using judgemental terms such as good or
bad control and aim to achieve good communication, understanding and cooperation.
77
Parameters of Glycaemic Control
Prior to 1978 urine testing was the only means of monitoring glycaemic control.
Unfortunately urine tests do not reliably reflect blood glucose values.11-14
Several different parameters are used to measure glycaemic control. These include:
• Blood glucose levels.
• Glycated haemoglobin (eg HbA1c).
• Glycated serum protein (eg fructosamine).
Blood Glucose Monitoring
Blood glucose measurement is essential in the management of children and adolescents with
diabetes for the following reasons:
• To monitor daily control.
• To detect hypoglycaemic and hyperglycaemic episodes.
• To make possible the safe management of acute illnesses at home.
The frequency of blood glucose monitoring should be adapted to the insulin regimen, the age
of the child and the stability of the diabetes. Frequent daily blood glucose monitoring as part
of a package of care is associated with improved glycaemic control.11;15
Older children and adolescents will be able to measure their own blood glucose levels
while the younger child will be dependent on his/her parent or care giver for glucose
monitoring.
Information obtained from blood glucose monitoring should be used in association with
HbA1c and clinical parameters to evaluate and modify management to improve glycaemic
control.
Timing of blood glucose testing
The blood glucose levels should be measured:
• At different times of the day pre- and post-prandially in order to obtain a profile over
the 24 hours.
• Before, during and after sport.
• During intercurrent illnesses.
• If hypoglycaemia is suspected.
• Following treatment for hypoglycaemia.
Most children on two injections a day do 3-4 tests a day; pre-breakfast, pre-dinner and the
third test at varying times to obtain pre-lunch, bedtime and night-time data.
More tests may be needed in multiple dose insulin regimens11 or for insulin pump use.
If the diabetes is very stable, then the frequency of testing may be reduced (eg to obtain a
profile over the day several times a week).11 Similarly if there is resistance to regular blood
glucose testing then a compromise situation of reduced testing should be negotiated with the
older child or adolescent.
Options for reduced testing include a:
• Full profile over the day several times a week with no intervening tests.
• Composite profile obtained by a single blood test each day taken at different time
points.
78
Techniques for blood glucose testing
Test strips and meters are sufficiently accurate and precise when used properly according to
the manufacturer’s instructions. Correct technique includes:
• Following manufacturer’s instructions.
• Washing and drying of hands (to reduce infection risk and to wash glucose off fingers).
• Calibrating the meter for the lot number of the reagent strips.
• Using control solutions periodically with known glucose concentrations to assess meter
accuracy.
• Performing the test within defined temperature and humidity limits.
• Use of sufficient blood for the strip.
• Proper storage of blood glucose reagent strips and use before expiry date.
Devices for blood glucose testing
Meters and Reagent Strips
Meters are available for bedside or self-monitoring of blood glucose levels. They are used in
conjunction with blood glucose reagent strips which can be divided into those which result in
a:
• Change of colour.
• Change in electrical current (bioelectric).
Those that depend on a change of colour can be read either visually against calibrated colour
blocks or with a reflectance blood glucose meter. Reflectance meters have largely been
superseded.
Most modern meters employ bioelectric strips that can only be read in the meter and
cannot be read visually. Bioelectric strips usually require less than 5 microlitres blood (a
large drop of blood measures 50 microlitres). Many meters are able to store results of
previous readings, including date and time of the reading. Some meters are able to download
the data to a computer and appropriate software programmes are able to transform the data
into a variety of display formats.
All children and adolescents should have an appropriate meter. Rebates for meters are
available to those in most health insurance plans. Families suffering financial hardship are
able to obtain these devices through various government safety-net schemes (details available
through diabetes centres and Diabetes Australia).
Finger-prickers and other prickers
Special spring-loaded finger-pricking devices are available in order to reduce pain. Some
devices are able to vary the depth of penetration by the lancet or utilise lancets with finer
gauges. These are highly recommended for use in children and adolescents. Other devices are
available which allow blood to be sampled from other parts of the body (eg forearm). There
is a strong correlation between forearm blood glucose monitoring and finger blood glucose
monitoring.16-20
Continuous glucose monitoring systems (CBGM)
Intermittent capillary blood glucose monitoring gives a limited glimpse of blood glucose
levels. CBGM may be a useful tool in giving detailed information on blood glucose trends
during stabilisation of diabetes or during initiation and monitoring of insulin pump therapy.21
Invasive and non-invasive types of CBGM exist. Both types of CBGM need to be calibrated
against capillary samples.
79
Invasive CBGM
Invasive CBGM monitoring systems available in Australia measure interstitial blood glucose
via an indwelling sensor in the subcutaneous tissue of the abdomen or buttocks. The glucose
levels measured by this technique correlate well with those obtained by conventional blood
glucose monitoring.22-25 These monitors give useful insight into the individual blood glucose
profile and are especially useful in detecting asymptomatic hypoglycaemia26;27 and may assist
in stabilisation and motivation of patients.28 At present they are only available for short-term
use in individual patients attending large paediatric centres.
Non-invasive CBGM
These devices have not been released in Australia.
• Electrochemical enzyme sensor
This device is worn like a wristwatch and provides frequent glucose readings. Glucose
is extracted non-invasively via reverse iontophoresis for collection in a gel disc
biosensor.29 The blood glucose readings correspond well with conventional finger prick
blood glucose monitoring (r = 0.85 in the clinic setting and 0.90 in the home settings).30
Mild skin reactions can occur at the site of the adhesive pad.31
• Infrared spectroscopy
Infrared spectroscopy technology is also being developed to measure blood glucose
non-invasively.32-34
Record keeping and review of records
A daily record of all testing performed should be kept in a logbook and this should be
reviewed frequently to ensure optimal adjustments in management are made.
The use of memory-glucose meters without daily reviewing of glucose levels is not
adolescent and the family, and appropriate changes in insulin dosage may not be made.
The record should be available at the time of consultation and should contain:
• Blood glucose levels.
• Time and date of test.
• Insulin dosage.
• Events which could influence metabolic control, such as birthday parties, illness,
exercise, menses, etc.
• Hypoglycaemic episodes.
A variety of logbooks are provided by different companies. It is necessary to choose the most
suitable for the child’s care. Depending on the child’s age, it is helpful to encourage his/her
involvement in documenting blood glucose levels and activities. There are logbooks for
young children that include stickers or diaries for teenagers which include a section for
recording blood glucose levels, insulin doses and activities.
The family should understand that the record book is not a ‘report card’ on which their
efforts will be judged, but rather a diary of blood glucose levels, insulin dosages and special
comments.
The causes of a discrepancy between the logbook and other indices of glycaemic control
(clinical, HbA1c) include:
• Poor technique of blood glucose measurements.
• Falsification of results.
80
•
Failure to test at different times in order to detect episodes of unsuspected
hyperglycaemia (eg testing pre-prandially only).
• Malfunction of the meter.
HbA1C
The most appropriate measure of long-term glycaemic control is the use of HbA1c, a
subfraction of glycated haemoglobin. It is the only measure of glycaemic control that has
been shown to be associated with long-term complications of diabetes and best reflects
glycaemic levels over the preceding 2-3 months.15;35
Glycated haemoglobin (HbA1) occurs in several variants and can be measured using
several different methods. Haemoglobin A1 contributes <10% of the total haemoglobin. Use
of cation-exchange chromatography has shown that haemoglobin A1 can be separated into at
lease three components HbA1a, HbA1b and HbA1c. These components have been found to be
elevated in diabetic patients. Studies have found a strong relationship between HbA1c and
fasting blood glucose levels over the preceding weeks in both adults and children with
diabetes, and in non-diabetic subjects.36;37 HbA1c is the most frequently used measure of
glycated haemoglobin in clinical practice.
HbA1c is detected by high-pressure cation-exchange chromatography, electrophoresis or
immunoturbidometric methods.15
The non-diabetic reference range for HbA1c should be established by each laboratory but is
approximately 4-6%.
The International Federation of Clinical Chemistry and Laboratory Medicine has
recommended the adoption of new reference ranges for HbA1c based on more accurate mass
spectroscopy methods. These would reduce the non-diabetic reference range for HbA1c by
1.5-2.0%. Currently the IFCC recommendations are being considered and if adopted,
extensive education would need to be provided to both patients and health care
professionals.38
The American Diabetes Association recommends measuring the HbA1c at least twice per
year in patients who are meeting treatment goals, and more frequently (quarterly) in those
whose treatment has changed or who are not meeting glycaemic goals.12 Other professional
bodies suggest similar monitoring.11;39 In Australia Medicare reimburses the cost of four
HbA1c measurements in any 12 month period. However in children under the age of 6 years
with unstable diabetes, Medicare reimburses six HbA1c measurements annually.
HbA1c results should be available at the time of the clinic visit, as this influences the
outcome of the consultation in a substantial proportion of cases.39;40 Although a HbA1c <7.5%
should be aimed for, the target that is achieved for an individual will depend on the
interaction of the many factors. In children under the age of 6 years, the HbA1c target may be
set a little higher because of the dangers of hypoglycaemia to the developing brain.
HbA1c values need to be interpreted in the context of blood glucose readings and clinical
parameters (eg a child with a low HbA1c may be experiencing asymptomatic hypoglycaemia).
Whilst treatment aims to achieve near normoglycaemia, it must be noted that even in the
DCCT, the mean HbA1c of the intensively treated adult group was still elevated at 7.2% (nondiabetic range <6.05%) and was 8.1% in the adolescent cohort of the study. It is relevant that
adolescents in the DCCT had significantly higher HbA1c levels than adults in both intensively
treated and conventionally treated groups. Despite these higher HbA1c levels they
experienced more severe and moderate hypoglycaemic episodes underlining the difficulties in
achieving ideal metabolic control in this age group.1;2
Children whose HbA1c is rising or persistently elevated should have all aspects of their
diabetes management reassessed.
81
Fructosamine
Fructosamine measures the glycation of serum proteins. The term ‘fructosamine’ refers to the
nature of the chemical bond between glucose and the amino acid on the protein and has
nothing to do with fructose. Because the turnover of albumin is more rapid than that of
haemoglobin, HbA1c and fructosamine measurements reflect different periods of blood
glucose control (3 months versus 3 weeks).12
Urine Testing for Glucose
Urinary glucose measurements are not recommended for monitoring glycaemic control
because of poor correlations between glucose levels in the blood and urine.11-14
Urinary glucose levels will not provide any information about hypoglycaemia (the renal
threshold for glycosuria is usually approximately 10 mmol/L).12
If blood glucose monitoring is not possible because of psychological reasons, then urine
tests using glucose-specific strips will at least provide some information.
The testing of urine for glucose reflects glycaemia a few hours preceding the test. The
accuracy of the test in evaluating glucose control may be increased if a urine test is performed
on a second specimen of urine obtained 30 minutes after initially emptying the bladder.
Urine testing for glucose is relatively inexpensive and is performed using glucose-specific
dipsticks for glucose alone, or combined with ketonuria testing or as part of a multiple urinetesting strip.
The manufacturer’s instructions suggest that a urinary glucose reading of:
• 5.5 mmol/L corresponds to a trace of glycosuria.
• 14 mmol/L corresponds to + of glycosuria.
• 28 mmol/L corresponds to + + of glycosuria.
• 55 mmol/L corresponds to + + + of glycosuria.
• 111 mmol/L corresponds to + + + + of glycosuria.
Testing for Ketones
Ketone acids include acetoacetic acid and beta-hydroxybutyric acid. Acetoacetic acid
spontaneously degrades to form a molecule of acetone and carbon dioxide. The blood levels
of beta-hydroxybutyric acid are usually four times that of acetoacetic acid.41 During hypoxia,
severe shock or when there is lactic acidosis, this ratio may be greatly increased and a
measure of the acetoacetic acid level may greatly underestimate the actual total level of
ketone acids.
The recently released meter and strips for bedside or home blood ketone testing measures
beta-hydroxybutyrate levels whereas urine ketone strips only measure acetoacetic acid.
Blood ketones
A meter that reliably measures blood ketone (beta-hydroxybutyrate) levels is available for
home or bedside use. Specific strips for this purpose need to be used. The manufacturer’s
instructions need to be followed carefully. The same meter, using different strips, can also be
used to measure blood glucose.
In a study of children measuring ß-hydroxybutyrate 8 times per day for 2 weeks, only
6.0% of the ß-hydroxybutyrate measurements were 0.2 mmol/L.42
82
As a general guide to aid interpretation of blood ketone readings the manufacturer’s
recommendations indicate:
• The normal range is <0.6 mmol/L.
• 0.6 - 1.5 mmol/L indicates developing ketosis.
• 1.5 mmol/L is significantly elevated and at risk of developing diabetic ketoacidosis.
Urine ketones
The testing of urine for the presence of ketonuria is an essential part of diabetes monitoring.
Urine test trips need to be stored in an airtight container and used within their expiry date as
per the manufacturer’s instructions.
The manufacturer’s instructions suggest that a urinary ketone reading of:
• 0.5 mmol/L corresponds to a trace of ketones.
• 1.5 mmol/L corresponds to small ketones.
• 4 mmol/L corresponds to moderate ketones.
• 8 mmol/L corresponds to large ketones.
Urine should be tested for ketones in the following circumstances:12;13;39;42
• If vomiting occurs.
• Any time the blood glucose is above 15 mmol/L, especially if the child or adolescent is
unwell and especially if the blood glucose has been high for more than 24 hours.
• If inappropriate drowsiness is present.
• In the presence of high temperature, vomiting or diarrhoea, even when the blood
glucose is <15 mmol/L.
• If abdominal pains occur.
• If breathing is rapid and suggestive of ketoacidosis.
• If the child or adolescent has flushed cheeks.
Ketonuria in the presence of hyperglycaemia is indicative of severe insulin deficiency and
calls for urgent therapy to prevent progression into ketoacidosis (see Chapter 9 and Chapter
11).
Ketonuria in the presence of low blood glucose levels is indicative of a starvation state or
is the result of a counter-regulatory response to hypoglycaemia. Persistent ketonuria in the
presence of hypoglycaemia may be seen in prolonged nausea and vomiting states. It is best
managed by an infusion of 5-10% dextrose in N/2 Saline at maintenance rates (plus
correction of dehydration if indicated) together with insulin to maintain the blood glucose at
5-10 mmol/L.
The Evidence
The evidence for the benefits of near patient testing of HbA1c at outpatient visits is listed in
Evidence Table 6.1.
• A quasi-randomised trial found that having the HbA1c result available at the time of the
clinic visit, influences the outcome of the consultation in a substantial proportion of
cases.40(III-1)
The evidence for the benefits of improved glycaemic control on development of
microvascular and macrovascular complications is listed in Evidence Table 6.2.
• The Diabetes Control and Complications Trial (DCCT) confirmed the benefit of
maintaining near normoglycaemia in reducing the development and progression of
diabetic microvascular complications in adolescents and adults.1;2(II)
83
•
In the DCCT there was no lower threshold of HbA1c below which the risk of
complications was eliminated, and any improvement in HbA1c conferred a reduction in
risk.3;4(II)
• Longer follow up of patients after the completion of the DCCT, in the EDIC
(Epidemiology of Diabetes Interventions and Complications) study showed increasing
reduction of microvascular and macrovascular complications with optimal early metabolic
control.5;6(II)
• In 1999 in NSW, fewer than 25% of children and adolescents had HbA1c levels <7.5%,
with the median HbA1c being 8.2% [interquartile range 7.6-9.1%].9;10(IV)
• Diabetes control should be optimised as much as possible as improved glycaemic control
reduces the risk of development and progression of microvascular and macrovascular
complications in adolescents and adults.1;2;3;4;5;6(II)
• Frequent daily blood glucose monitoring as part of a package of care has been shown to be
associated with improved glycaemic control.15(T)
• The frequency of blood glucose monitoring should be adapted to the insulin regimen, the
age of the child and the stability of the diabetes.11(C)
• The use of memory-glucose meters without daily reviewing of glucose levels is not
adolescent and the family, and appropriate changes in insulin dosage may not be
made.43(C)
• HbA1c is the only measure of glycaemic control that has been shown to be associated with
long-term complications of diabetes and best reflects glycaemic levels over the preceding
2-3 months.15(T)
• The American Diabetes Association recommends measuring the HbA1c at least twice per
year in patients who are meeting treatment goals, and more frequently (quarterly) in those
whose treatment has changed or who are not meeting glycaemic goals.12(C)
• HbA1c results should be available at the time of the clinic visit as this may influence the
outcome of the consultation.40(III-1)
11;39
• In older children and adolescents the target HbA1c should be <7.5%.
(T,C)
• Increased efforts to improve glycaemic control are recommended as fewer than 25% of
children and adolescents in NSW had HbA1c levels <7.5%.9;10(IV)
• In younger children, the HbA1c target may be set a little higher because of the dangers of
hypoglycaemia to the developing brain.11(C)
• HbA1c values need to be interpreted in the context of blood glucose readings and clinical
parameters (eg a child with a low HbA1c may be experiencing asymptomatic
hypoglycaemia).39(C)
• Children whose HbA1c is rising or persistently elevated should have all aspects of their
diabetes management reassessed.11(C)
• Ketones should be tested for when the blood glucose is above 15 mmol/L and the child or
adolescent is unwell.39(C)
• Ketones should be tested for in the presence of abdominal pains, rapid breathing, flushed
cheeks, high temperature, vomiting, diarrhoea or inappropriate drowsiness even when the
blood glucose is <15 mmol/L.43(C)
I = Evidence from a systemic review of all relevant RCT’s
II = Evidence from at least one properly designed RCT
84
III-1 = Evidence from well-designed pseudo-randomised controlled trials
Reference List
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DCCT Research Group: The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in
the diabetes control and complications trial. Diabetes 44:968-983, 1995
Trial, Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes therapy and carotid intimamedia thickness in type 1 diabetes mellitus. New England Journal of Medicine 348:2294-2303, 2003
139:804-812, 2001
Smith AHK: The National Paediatric Diabetes Audit. Annual Report. Diabetes UK30, 2001
American Diabetes Association: ADA position statement. Urine glucose and ketone determination. Clinical practice
recommendations 1995. Diabetes Care 18(suppl):20, 1995
Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM: Tests of glycemia in diabetes. Diabetes Care 18:896-909,
1995
Coster S, Gulliford MC, Seed PT, Powrie JK, Swaminathan R: Monitoring blood glucose control in diabetes mellitus: a systematic
review. Health Technology Assessment 4:1-93, 2000
Lock JP, Szuts EZ, Malomo KJ, Anagnostopoulos A, Rao S.: Accuracy of alternate site testing - Comparing arm and finger blood
glucose results in glucose dynamic states. Diabetes Technology and Therapeutics 4:89, 2002
Fineberg SE, Bergenstal RM, Bernstein R., Laffel LM, Schwartz SL: Use of an automated device for alternative site blood glucose
monitoring. Diabetes Care 24:1217-1220, 2001
Lee DM, Weinert SE, Miller EE: A study of forearm versus finger stick glucose monitoring. Diabetes Technology and Therapeutics
4:13-23, 2002
McGarraugh G, Price D, Schwartz S, Weinstein R: Physiological influences on off-finger glucose testing. Diabetes Technology and
Therapeutics 3:367-376, 2001
Peled N, Wong D, Gwalani SL: Comparison of glucose levels in capillary blood samples obtained from a variety of body sites.
Diabetes Technology and Therapeutics 4:35-44, 2002
McGahan L.: Continuous glucose monitoring in the management of diabetes mellitus. Issues in Emerging Health Technologies 1-4,
2002
Gross TM, Bode BW, Einhorn D, Kayne DM, Reed JH, White NH: Performance evaluation of the MiniMed continuous glucose
monitoring system during patient home use. Diabetes Technology and Therapeutics 2:49-56, 2000
Gross TM, Ter Veer A: Continuous glucose monitoring in previously unstudied population subgroups. Diabetes Technology &
Therapeutics 2 Suppl 1:S27-S34, 2000
Gross TM, Mastrototaro JJ: Efficacy and reliability of the continuous glucose monitoring system. Diabetes Technology &
Therapeutics 2 Suppl 1:S19-S26, 2000
Maran A, Crepaldi C, Tiengo A, GG, Vitali E, Pagano G: Continuous subcutaneous glucose monitoring in diabetic patients: a
multicenter analysis. Diabetes Care 25:347-352, 2002
Schiaffini R, Ciampalini P, Fierabracci A, Spera S, Borrelli P, Bottazzo GF: The continuous glucose monitoring system (CGMS) in
type 1 diabetic children is the way to reduce hypoglycemic risk. Diabetes/Metabolism Research Reviews 18:324-329, 2002
Chase HP, Kim LM, Owen SL, MacKenzie TA, Klingensmith GJ, Murtfeldt R, Garg SK: Continuous subcutaneous glucose
monitoring in children with type 1 diabetes. Pediatrics 107:222-226, 2001
Ludvigsson J, Hanas R: Continuous subcutaneous glucose monitoring improved metabolic control in pediatric patients with type 1
diabetes: a controlled crossover study. Pediatrics 111:933-938, 2003
Tierney MJ, Tamada JA, Potts RO, Jovanovic L, Garg S, Cygnus Research Team.: Clinical evaluation of the GlucoWatch
biographer: a continual, non-invasive glucose monitor for patients with diabetes. Biosensors & Bioelectronics 16:621-629, 2001
Garg SK, Potts RO, Ackerman NR, Fermi SJ, Tamada JA, Chase HP: Correlation of fingerstick blood glucose measurements with
GlucoWatch biographer glucose results in young subjects with type 1 diabetes. Diabetes Care 22:1708-1714, 1999
Eastman RC, Chase HP, Buckingham B, Hathout EH, Fuller-Byk L, Leptien A, Van Wyhe MM, Davis TL, Fermi SJ, Pechler H,
Sahyun G, Lopatin M, Wang BY, Wei C, Bartkowiak M, Ginsberg BH, Tamada JA, Pitzer KR: Use of the GlucoWatch biographer
in children and adolescents with diabetes. Pediatric Diabetes 3:127-134, 2002
Gabriely I, Wozniak R, Mevorach M, Kaplan J, Aharon Y, Shamoon H: Transcutaneous glucose measurement using near-infrared
spectroscopy during hypoglycemia. Diabetes Care 22:2026-2032, 1999
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Muller UA, Mertes B, Fischbacher C, Jageman KU, Danzer K: Non-invasive blood glucose monitoring by means of near infrared
spectroscopy: methods for improving the reliability of the calibration models. International Journal of Artificial Organs 20:285290, 1997
Uemura T, Nishida K, Sakakida M, Ichinose K, Shimoda S, Shichiri M: Noninvasive blood glucose measurement by Fourier
transform infrared spectroscopic analysis through the mucous membrane of the lip: application of a chalcogenide optical fiber
system. Frontiers of Medical and Biological Engineering 9:153, 1999
Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE: Defining the Relationship Between Plasma
Glucose and HbA1c: Analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care
25:275-278, 2002
Mortensen HB.: Glycated hemoglobin. Reaction and biokinetic studies. Clinical application of hemoglobin A1c in the assessment of
metabolic control in children with diabetes mellitus. Danish Medical Bulletin 32:309-328, 1985
Mortensen HB, Vestermark S, Kastrup KW: Metabolic control in children with insulin dependent diabetes mellitus assessed by
hemoglobin A(1c). Acta Paediatrica Scandinavica 71:217-222, 1982
Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, Miedema K, Mosca A, Mauri P, Paroni R, Thienpont L, Umemoto
M, Weykamp C: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Approved IFCC reference
method for the measurement of HbA1c in human blood. Clinical Chemistry & Laboratory Medicine 40:78-89, 2002
Grieve R, Beech R, Vincent J, Mazurkiewicz J: Near patient testing in diabetes clinics: appraising the costs and outcomes. Health
Technology Assessment 3:1-74, 1999
Laffel L: Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metabolism
Research and Reviews 15:412-426, 2000
Samuelsson U, Ludvigsson J: When should determination of ketonemia be recommended? Diabetes Technology & Therapeutics
4:645-650, 2002
86
Chapter 7: Nutrition
Nutrition is a fundamental component in the management of diabetes.1
There are few long-term studies to support current dietary recommendations, particularly
for children. Nutritional management of children and adolescents with type 1 diabetes should
be by an accredited practising dietitian trained in paediatric diabetes.
Nutrition Therapy
The aims of nutrition therapy in type 1 diabetes are to ensure:
• Adequate energy and nutritional intake for normal growth and development.
• Optimal glycaemic control without severe hypoglycaemic and/or prolonged
hyperglycaemic episodes.
• Optimal blood lipid control.
• Meeting the psychosocial needs of the individual by incorporating food and insulin
regimens into usual eating habits, appetite, usual routines and exercise patterns.
Nutritional Assessment
Nutritional assessment on initial diagnosis should include:
• Family history of diabetes, including:
Parental beliefs about diabetes.
Individual beliefs about diabetes.
• Medical history- including conditions that may impact on dietary intake.
• Social situation- family structure, cultural background and influences.
• Growth (height and weight, including growth history, BMI) and development.
• Diet history to establish usual dietary intake including energy intake, total and saturated
fat, carbohydrate intake and distribution, variations in appetite and usual food
preferences.
• Usual routines and activities, including organised sport, school/pre-school timetables,
after-school activities and any variations including weekend variations.
• Parent/child’s learning ability and motivation to ensure appropriate nutrition
intervention.
Nutrition Review
Ongoing nutritional monitoring of the individual with diabetes by a dietitian experienced with
paediatric diabetes management is essential.
The initial review should occur 2-4 weeks post-diagnosis. Ongoing reviews should occur
every 12 months or more often depending on the age of the child or the needs of the
child/family.
Ongoing review should include:
• Usual nutritional intake including appetite satisfaction.
• Growth including height, weight and BMI centiles (Figures 7.1 and 7.2).
• Insulin regimen including any regular insulin adjustments.
• HbA1c and day to day blood glucose monitoring including patterns of hypo- or hyperglycaemia.
• Method of treatment of hypoglycaemia.
• Exercise regimen and carbohydrate intake pre-exercise.
87
•
•
Individual or parental concerns about dietary management.
Assessment of changes in lifestyle impacting on dietary intake and quality of life (eg
body image perception, alcohol, cigarettes and/or drugs depending on the age of the
child).
• Re-education where required, including education of the individual with diabetes as
he/she becomes older and increasingly more responsible for self-care.
• Consideration of new medical conditions that may impact on management (eg
hypercholesterolemia, coeliac disease, bulimia, family history of newly diagnosed
cardiovascular disease).
Dietary Recommendations
There is no research on the nutrient requirements for children and adolescents with diabetes;
therefore nutrient recommendations are based on requirements for all healthy children and
adolescents. These recommendations are summarised by the ‘The Dietary Guidelines for
Children and Adolescents in Australia’ (Table 7.1).2
The recommended meal plan should consider the child’s usual appetite and food intake
pattern. Some modification to usual intake may be necessary to reduce saturated fat intake
and sugars intake and to distribute carbohydrate evenly over regular meals and snacks.
Table 7.1: The Dietary Guidelines for Children and Adolescents in Australia
Encourage and support breastfeeding
Children and adolescents need sufficient nutritious foods to grow and develop normally
• Growth should be checked regularly
• Physical activity is important for all children and adolescents
Enjoy a wide variety of nutritious foods
Children and adolescents should be encouraged to:
• Eat plenty of vegetables, legumes and fruits
• Eat plenty of cereals (including breads, rice, pasta and noodles), preferably wholegrain
• Include lean meat, fish, poultry and/or alternatives
• Include milks, yoghurts, cheese and/or alternatives
• Reduced-fat milks are not suitable for young children under 2 years, because of their
high energy needs, but reduced fat varieties should be encouraged for older children
and adolescents
• Choose water as a drink
And care should be taken to:
• Limit saturated fat and moderate total fat intake (NB low fat diets are not suitable for
infants)
• Choose foods low in salt
• Consume only moderate amounts of sugars and foods containing added sugars
Care for your child’s food: prepare and store it safely
Source: Dietary Guidelines for Children and Adolescents (National Health and Medical Research Council 2003)
Energy Intake
Many children have increased energy requirements initially to allow for regain of lost
weight.3 Children and adolescents with established and stable diabetes have the same basic
energy requirements as their peers. The estimates of energy requirements are made from an
88
individual’s food nutrition history of a typical daily intake obtained from 24 hr recall or a 3day food record.
Consideration needs to be given to changing appetite and activity levels. Individual
adjustment is required with regular monitoring of growth using standard height and weight
charts ideally at 3-6 month intervals.3
Dietary Carbohydrate
A diet providing 50-55% total energy as carbohydrate is recommended for children and
adolescents with diabetes.2
Carbohydrates directly affect the blood glucose level and the amount, timing and type of
carbohydrate need to be considered in relation to the insulin regimen.1;4
Practical quantification of carbohydrate intake is necessary as part of management.5
Methods of carbohydrate quantification include use of 15 gm carbohydrate exchanges or
the use of the individual’s usual serving size as the basis for the meal plan.6
In practice, carbohydrate amounts are suggested for each meal and snack for those on
fixed insulin doses that are based on the individual’s previous dietary intake, activity, appetite
and insulin regimen.
Day to day consistency in carbohydrate intake is important for those receiving fixed doses
of insulin.1
Prescriptive meal plans are not recommended. Compliance is poor with rigid prescriptive
meal plans and quality of life is decreased.6 The DCCT and the Dose Adjustment for
Normalised Eating (DAFNE) Study which included adolescents on intensive insulin therapy
demonstrated better metabolic outcomes are achieved if insulin is adjusted for carbohydrate
quantity.4;7
For those on multiple daily injections or pump therapy a 1% decrease in HbA1c can be
achieved by adjusting meal time insulin doses based on carbohydrate quantities.4
Glycaemic Index (GI)
The GI is a ranking of foods based on their acute glycaemic impact compared to the reference
standard glucose.8 The GI is one of several tools used to assist with glycaemic control.
Carbohydrates with a low GI result in a slower and more gradual rise in blood glucose
levels and reduce the postprandial glycaemic response compared to carbohydrates with a
higher GI.
Low GI food sources include wholegrain breads, legumes, pasta, temperate fruits, dairy
foods. Not all low GI foods are good everyday choices (eg chocolate, fructose) (see table
7.2).
Many factors may influence a food’s glycaemic response. However, the ranking of foods
on the basis of their GI value is generally consistent.9 The GI is also reproducible and
predictable within the context of mixed meals10;11;12 and has also been shown to have a
clinically important ‘carry-over’ effect on the subsequent meal.13
It has been suggested that low-GI diets are difficult to understand, may limit food choice
and variety and deteriorate overall dietary quality.14;15 However, studies have shown that low
GI diets are easy to understand, and have no detrimental effect on food variety or nutritional
quality.6;16
A recent meta-analysis comparing low GI diets with conventional or high GI diets, using
glycaemic control (HbA1c or fructosamine) as the outcome measure concluded that low GI
diets have a small but clinically useful effect on medium term glycaemic control.17 This
meta-analysis analysed both adult and paediatric studies together.17 There were only two
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paediatric studies which have investigated low GI diets in children and adolescents with type
1 diabetes.6;16;18 The larger study, a randomised controlled trial, showed that a flexible low-GI
diet resulted in a significantly better HbA1c outcome after 12 months (8.05 ±0.95 vs. 8.61
±1.37%, p = 0.05) and a better reported quality of life, with no decrease in number of food
choices or macronutrient composition compared to a measured 15g carbohydrate exchange
diabetic diet.6;16 The other study was of short duration (6 weeks) with only 7 patients
enrolled, and although the glycated serum albumin was lower in the patients who received a
low GI diet, these patients also had a higher daily fibre intake.18
Table 7.2: The Glycaemic Index of Some Foods (Glucose = 100)12
Low GI Foods (<55)
Moderate GI Foods (55-69) High GI Foods (70)
Fructose 20
Lactose 57
White bread 70
Whole milk 27
Honey 58
Watermelon 72
Apple 36
Sucrose 59
Waffles 76
Apple juice 41
Basmati rice 59
Wholemeal bread 77
Apple muffin 44
Banana 60
Puffed Wheat 80
Fruit loaf 47
Regular ice-cream 61
Jelly beans 80
Sweet potato 48
Shortbread 64
Baked potato 85
Chocolate 49
Crumpet 69
Honey-glucose enriched 87
Rolled oats 50
Pasta 50
Foster-Powell, Holt et al., 2002
Sugars
The term sugars is conventionally used to describe monosaccharides (eg glucose, fructose)
and disaccharides such as sucrose and lactose. These can be found naturally in foods or can
be added in processing. Sugar, by contrast, is used to describe purified sucrose, as are the
terms refined sugar and added sugar. The term no added sugar means no sugars have been
added during the manufacturing process; it does not mean that no sugar or other sugars are
present, since most foods contain sugars in some form.
Australian school children consume about 50% of their daily energy intake as
carbohydrates, with total sugars contributing 25% of energy intake (15% as added sugars and
10% as natural sugars).19 A recent WHO/FAO report on population nutrition strategies to
reduce obesity, cardiovascular disease and diabetes recommends that added sugars be
reduced to <10% of daily energy intake.20
Dietary guidelines for children and adolescents recommend the consumption of moderate
amounts of sugars and foods containing added sugars.2
When sucrose is the main ingredient, such as in soft drinks and cordials, choosing the
sugar-free alternative is desirable.
Overall, the evidence supports moderate use of sugars (including sucrose) in the diabetes
diet.21-25
Artificially sweetened products
There are two main types of artificial sweeteners:
• Nutritive.
• Non-nutritive.
Nutritive sweeteners include fructose and polyols (sugar alcohols such as sorbitol, mannitol
and xylitol). Foods containing these sweeteners are often labelled as ‘carbohydrate modified’.
90
They are only partially absorbed from the small intestine and excessive use will cause
diarrhoea in children.26
Non-nutritive sweeteners include aspartame, saccharin, sucralose and acesulfame K. All
have been extensively studied for safety and their use in food products in Australia is
governed by the Food Standards Code for Australia and New Zealand.
Fibre
The Australian Dietary Guidelines aim to ensure adequate dietary fibre intake (soluble and
insoluble). High fibre diets help to prevent constipation and optimise bowel health. An
adequate fibre intake is calculated using the age of the child (years) plus 5 gm.27
Controversy remains whether high fibre diets have direct effects on glycaemic control.28-30
Dietary Fat Intake
The major types of dietary fats are:
• Saturated (animal fats including dairy, meat and butter).
• Monounsaturated (olive and canola oils).
• Polyunsaturated fats (vegetable fats including margarine and vegetable oils).
The Australian Dietary Guidelines for Children and Adolescents recommend limiting
saturated fat intake and moderate total fat intake.2 The recommended targets for fat intakes do
not differ for children with diabetes (Table 7.3).
Table 7.3: Summary of the Australian Dietary Guidelines for Dietary Fat Intake during
Childhood
Age Group
Recommendations
Birth to two years • during the first 6 months fat should compromise 50% total
of age
energy intake by breast milk or formula.
• from 6-12 months the target is 40% total energy.
• skim milk and reduced fat milk should not be used in children
under the age of two years.
Two to five years
• target is 30% total energy from fat.
• no more than 10% energy from saturated fat.
• reduced fat milks are suitable but not skim milk.
Five to fourteen
• no more than 10% total energy from saturated fat.
years
Adolescence
• no more than 10% total energy from saturated fat.
Source: (National Health and Medical Research Council 2003).
The National Nutrition Survey (1995) reported that children and adolescents in the general
population (2-18 years) had an average intake of 33% total energy from fat.31 Children with
diabetes have similar high fat intakes ranging between 33%-36% total energy.16;32
International recommendations for nutrition in the population have recommended the diet
contain 30% of energy from fat, with saturated fats contributing less than 10% of total
energy, while polyunsaturated and monounsaturated fats each contribute more than 10% to
the daily energy content.20
91
Protein
Protein should provide approximately 15-20% of total energy intake for children and
adolescents.
Lean sources of protein are recommended which include lean cuts of meat and fat-reduced
dairy products as appropriate.
High protein, low carbohydrate diets are not generally recommended for children and
adolescents with diabetes. There are no studies that investigate the long-term effects of such
diets on the growth and development in children. Restricting carbohydrate intake may impact
on the nutritional adequacy of the diet and may cause hypoglycaemia. High protein diets
result in ketosis, which may result in dehydration, loss of appetite, irritability, lethargy, loss
of lean body mass and other abnormalities.33
Variations in Advised Meal Patterns and Insulin Regimens
There are numerous variations in insulin regimens that are used to manage type 1 diabetes in
children and adolescents. Expert nutritional guidance is an essential component of the overall
management.
Twice daily injection regimen
This usually involves a combination of short/rapid-acting and intermediate-acting insulin
injected twice daily, usually before breakfast and the evening meal. The meal plan should
consist of three meals and three snacks a day based on carbohydrate-containing foods. Meals
and snacks should not be missed or delayed (toddlers, however, tend to graze over the day).
Three injections per day
A mixture of short/rapid-acting and intermediate-acting insulin given before breakfast,
short/rapid-acting insulin before the afternoon snack or main evening meal and intermediateacting insulin in the evening is commonly used in older children and teenagers when a 2
injection per day regimen is inadequate.
Multiple daily injection regimens
This usually involves a total of four injections per day with short/rapid-acting insulin given
three times daily before breakfast, lunch and dinner and either intermediate- or long-acting
insulin given at supper. The suggested meal plan is three main meals and an evening snack
based on carbohydrate foods. Morning tea and afternoon tea snacks are not necessary but
may still be eaten if desired (this may influence choice of rapid-acting versus short-acting
insulin). This regimen allows some increased flexibility in meal timing and in the
carbohydrate quantity for meals, and is usually better suited to the lifestyle of the older child
or adolescent. For those requiring a large afternoon tea the pre dinner short/rapid-acting
insulin may be given before afternoon tea.
Insulin pump therapy
Insulin pump therapy provides basal insulin with additional insulin bolus doses for each
carbohydrate-containing meal/snack consumed (see insulin pump adjustment). It provides a
greater degree of flexibility, especially in relation to the diet. Meal and snack times can be
delayed or omitted and/or the carbohydrate content can be varied with the insulin bolus
adjusted accordingly.
92
Intensified glycaemic control coupled with greater food flexibility (quality and quantity)
can lead to undesirable weight gain. It is prudent to monitor closely for undesirable weight
gain and to encourage healthy eating habits including 3 main meals per day.
Age-group Specific Advice
Approaches to the management of diabetes vary greatly at different ages and stages of
development.
Infants
Exclusive breastfeeding for the first 6 months is recommended for all infants.2 If the mother
chooses not to breastfeed, an appropriate infant formula should be used. Regular breast or
bottle feeds (approx 3 hourly) will help to maintain blood glucose levels. Introduction of
solids is recommended at around 6 months similar to other infants.
Toddlers
Tantrums, food fads and food refusal are common toddler behaviours. Such behaviours in a
toddler with diabetes increase parental anxiety and accentuate problem meal behaviours.34
Toddlers eat erratically and have unpredictable activity levels. Rigid meal plans of three
meals and three snacks per day are impractical and not recommended. It is normal for
toddlers to ‘graze’ throughout the day. Appetite will fluctuate and toddlers generally regulate
their own intakes.
Practical advice includes substituting carbohydrate foods for those refused without
offering excessive choices, maximising carbohydrate finger foods and monitoring blood
glucose levels regularly if parents feel that there has been insufficient intake of carbohydrate
foods. Toddlers are encouraged to eat the family’s usual meals. Parents should not offer too
many choices, substitute carbohydrate foods with ‘junk foods’, or force feed their child as
this may encourage negative food related behaviours.
Primary school-aged children
Children’s energy needs constantly increase as they grow and increase their activity. Weight
gain is about 2.5 to 3 kg/year in boys and girls from 6 to 12 years of age, with energy intakes
nearly doubling in this time. Frequent review of meal plans is essential.
School-age children are encouraged to carry ‘hypo food’ and be aware of the need for
extra carbohydrate for exercise.
School introduces increasing peer influence and more independence, with less direct
parental supervision. Issues such as lunch swapping, forgetting to eat meals, throwing away
food and purchasing foods independently from school canteens need to be addressed.
Adolescents
In adolescence, growth patterns and nutrient requirements change rapidly.
Eating habits may include large afternoon tea, skipped meals, increased snacking, more
meals away from home, increased intake of high fat convenience foods and frequent
consumption of sweets and soft drinks.35
There is also increased influence of peer pressure about issues such as sexuality, body
weight and dieting, experimentation with alcohol, cigarettes and drugs and challenging
boundaries, including those related to diabetes self-management (see Chapter 18) for
discussion on insulin purging, insulin omission and eating disorders in adolescence).
Many adolescents manage their diabetes on a basal-bolus insulin regimen which provides
greater flexibility. However, special attention should be given to adolescents on multiple
93
injections because of the two-fold increased risk of obesity and increased incidence of severe
hypoglycaemia.36
The Evidence
The evidence for the benefits of low glycaemic index diets in the management of type 1
diabetes in children and adolescents is listed in Evidence Table 7.1.
17
6;16;18
• A recent meta-analysis (including mostly adult but some paediatric studies
)
comparing low GI diets with conventional or high GI diets, using glycaemic control
(HbA1c or fructosamine) as the outcome measure concluded that low GI diets have a small
but clinically useful effect on medium term glycaemic control.17(I)
The evidence for the benefits of adjusting insulin dose for carbohydrate quantity in the
management of type 1 diabetes in children and adolescents is listed in Evidence Table 7.2.
• The DCCT and the Dose Adjustment for Normalised Eating (DAFNE) Study which
included adolescents on intensive insulin therapy demonstrated better metabolic outcomes
are achieved if insulin is adjusted for carbohydrate quantity.4;7(II)
The evidence for the effect on glycaemic control of the moderate use of sugars in children
and adolescents with type 1 diabetes is listed in Evidence Table 7.3.
• Five small RCTs show that moderate use of sugars (including sucrose) in the diabetes diet
does not adversely affect glycaemic control.21-25(II)
• Nutrition is a fundamental component in the management of type 1 diabetes in childhood
and adolescence.1;3(C)
• Nutritional management of children and adolescents with type 1 diabetes should be
initiated by an accredited practising dietitian trained in paediatric diabetes.37(C)
• Nutritional reviews should occur 2-4 weeks post-diagnosis and ongoing at least once per
year by a paediatric dietitian experienced in diabetes management.37(C)
• Children and adolescents with diabetes should be encouraged to follow the NHMRC
Dietary Guidelines for Children and Adolescents in Australia which recommend that:2
Carbohydrate should provide 50-55% of total energy intake.
Dietary fat intake should provide between 25 and 40% of total energy intake
depending on the child’s age.
Saturated fat intake should be limited to <10% of total energy intake.
Dietary protein intake should provide 15-20% of total energy intake.(C)
• Children and adolescents with diabetes should be educated and encouraged to adjust their
insulin dose depending upon carbohydrate quantity.4;7(II)
• Day to day consistency in carbohydrate intake is important for those receiving fixed doses
of insulin.(C)
• Dietary advice should include information about low glycaemic index food as this can
help to improve glycaemic control.6;16;17;18(I)
• Moderate use of sucrose in the diabetes diet should be allowed as it does not significantly
influence glycaemic control in type 1 diabetes.21-25(II)
I = Evidence obtained from a systematic review of all relevant randomised controlled trials
II = Evidence obtained from at least one properly designed randomised controlled trial
94
Figure 7.1: Body Mass Index-for-age Percentiles: Girls, 2-20 Years
95
Figure 7.2: Body Mass Index-for-age Percentiles: Boys, 2-20 Years
96
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American Diabetes Association: Evidence-based nutrition principles and recommendations for the treatment and prevention of
diabetes and related complications. Diabetes Care 26 Suppl 1:S51-S61, 2003
NHMRC. Dietary Guidelines for Children and Adolescents in Australia incorporating the Infant Feeding Guidelines for Health
Workers. 2003. Ref Type: Report
Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister LA, Hoogwerf B, Mayer-Davis E, Mooradian AD,
Purnell JQ, Wheeler M: Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes
and Related Complications. Diabetes Care 25:148, 2002
Delahanty LM, Halford BN: The role of diet behaviours in achieving improved glycemic control in intensively treated patients in
the Diabetes Control and Complications Trial. Diabetes Care 16:1453-1458, 1993
Gilbertson HR, Brand-Miller JC, Thorburn AW, Evans S, Chondros P, Werther GA: The effect of flexible low glycemic index
dietary advice versus measured carbohydrate exchange diets on glycemic control in children with type 1 diabetes. Diabetes Care
24:1137-1143, 2001
DAFNE Study Group: Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes:
dose adjustment for normal eating (DAFNE) randomised controlled trial. British Medical Journal 325:746, 2002
Jenkins DJ, Wolever TM, Taylor RH, Barker H, Fielden H, Baldwin JM, Bowling AC, Newman HC, Jenkins AL, Goff DV:
Glycemic index of foods: a physiological basis for carbohydrate exchange. American Journal of Clinical Nutrition 34:362-366,
1981
Wolever TM, Jenkins DJ, Jenkins AL, Josse RG: The glycemic index: methodology and clinical implications. American Journal of
Clinical Nutrition 54:846-854, 1991
Lafrance L, Rabasa-Lhoret R, Poisson D, Ducros F, Chiasson JL: Effects of different glycaemic index foods and dietary fibre intake
on glycaemic control in type 1 diabetic patients on intensive insulin therapy. Diabetic Medicine 15:972-978, 1998
Wolever TM, Jenkins DJ: The use of the glycemic index in predicting the blood glucose response to mixed meals. American
Journal of Clinical Nutrition 43:167-172, 1986
Foster-Powell K, Holt SH, Brand-Miller JC: International table of glycemic index and glycemic load values. American Journal of
Clinical Nutrition 76:5-56, 2002
Wolever TM, Jenkins DJ, Ocana AM, Rao VA, Collier GR: Second-meal effect: low-glycemic-index foods eaten at dinner improve
subsequent breakfast glycemic response. American Journal of Clinical Nutrition 48:1041-1047, 1988
Beebe C: Diets with a low glycemic index: Not ready for practice yet. Nutrition Today 34:82-86, 1999
Franz MJ: In defence of the American Diabetes Association's recommendation on the glycemic index. Nutrition Today 34:78-81,
1999
Gilbertson HR, Thorburn AW, Brand-Miller JC, Chondros P, Werther GA: Effect of low-glycemic-index dietary advice on dietary
quality and food choice in children with type 1 diabetes. American Journal of Clinical Nutrition 77:83-90, 2003
Brand-Miller JH: Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials.
Diabetes Care 26:2261-2267, 2003
Collier GR, Giudici S, Kalmusky J, Wolever TM, Helman G, Wesson V, Ehrlich RM, Jenkins DJ: Low glycaemic index starchy
foods improve glucose control and lower serum cholesterol in diabetic children. Diabetes Nutrition and Metabolism 1:11-19, 1988
Cobiac L, Record S, Leppard P, Syrette J, and Flight I. Sugars in the Australian Diet: results from the 1995-96 National Nutrition
Survey. CSIRO. 2001. Adelaide.
WHO Technical Report Series. Diet, Nutrition and the Prevention of Chronic Disease. Report of a Joint WHO/FAO Expert
Consultation. 2003. Ref Type: Report
Loghmani E R: Glycemic response to sucrose-containing mixed meals in diets of children of with insulin-dependent diabetes
mellitus. Journal of Pediatrics 119:531-537, 1991
Rickard KA, Loghmani ES, Cleveland JL, Fineberg NS, Freidenberg GR: Lower glycemic response to sucrose in the diets of
children with type 1 diabetes. Journal of Pediatrics 133:429-434, 1998
Schwingshandl J: Effect of the introduction of dietary sucrose on metabolic control in children and adolescents with type I diabetes.
Acta Diabetologia 31:205-209, 1994
Wang SR, Chase HP, Garg SK, Hoops SL, Harris MA: The effect of sugar cereal with and without a mixed meal on glycemic
response in children with diabetes. Journal of Pediatric Gastroenterology & Nutrition 13:155-160, 1991
Wise JE, Keim KS, Huisinga JL, Willmann PA: Effect of sucrose-containing snacks on blood glucose control. Diabetes Care
12:423-426, 1989
Payne ML, Craig WJ, Williams AC: Sorbitol is a possible risk factor for diarrhoea in young children. Journal of the American
Dietetic Association 97:532-534, 1997
Williams CL, Bollella M, Wynder EL: A new recommendation for dietary fiber in childhood. Pediatrics 96:t-8, 1995
Buyken AE, Toeller M, Heitkamp G, Vitelli F, Stehle P, Scherbaum WA, Fuller JH: Relation of fibre intake to HbA(1c) and the
prevalence of severe ketoacidosis and severe hypoglycaemia. Diabetologia 41:882-890, 1998
Giacco R: Long-term dietary treatment with increased amounts of fiber-rich low-glycemic index natural foods improves blood
glucose control and reduces the number of hypoglycemic events in type 1 diabetic patients. Diabetes Care 23:1461-1466, 2000
Lindsay AN, Hardy S, Jarrett L, Rallison ML: High-carbohydrate, high-fiber diet in children with type I diabetes mellitus. Diabetes
Care 7:63-67, 1984
McLennan W, Podger A. National Nutrition Survey: nutrient intake and physical measurements. Canberra, Australian Bureau of
Statistics. 1997
Wiltshire EJ, Hirte C, Couper JJ: Dietary Fats Do Not Contribute to Hyperlipidemia in Children and Adolescents With Type 1
Diabetes. Diabetes Care 26:1356, 2003
St Jeor ST, Howard BV, Prewitt TE, Bovee V, Bazzarre T: Dietary protein and weight reduction: a statement for healthcare
professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart
Association. Circulation 104:1869-1874, 2001
Powers SW, Byars KC, Mitchell MJ, Patton SR, Standiford DA, Dolan LM: Parent Report of Mealtime Behavior and Parenting
Stress in Young Children With Type 1 Diabetes and in Healthy Control Subjects. Diabetes Care 25:313, 2002
Magrath G, Hartland BV: Dietary recommendations for children and adolescents with diabetes: an implementation paper. British
Diabetic Association's Professional Advisory Committee. Diabetic Medicine 10:874-885, 1993
97
36.
37.
139:804-812, 2001
98
Need for Physical Activity and General Recommendations
The benefits of regular physical activity for people of all ages are well known and accepted.1
Physical activity is more than organised sport and includes playing at school, running,
walking, dancing and other activities of daily living. The benefits of physical activity include
improved insulin sensitivity, weight management, musculo-skeletal benefits, functional
movement development, psychological wellbeing, social interaction and cardiovascular
fitness. There is no evidence to say that these benefits are not the same for people with
diabetes.2
As diabetes is associated with an increased risk of macrovascular disease, the benefit of
physical activity in improving known risk factors for atherosclerosis (eg overweight/obesity,
hypertension, hypercholesterolaemia) should be remembered.3
Education of the child with type 1 diabetes and their carer should include insulin
administration, blood glucose control, carbohydrate intake and management of
hypoglycaemia prior to undertaking any physical activity.
Children and adolescents with type 1 diabetes should be encouraged to participate in sport
and not be limited in their choice of activity.4 However, certain sports require special
consideration and others are contraindicated in people with insulin treated diabetes.
Activities should be approached with caution if they are solo in nature, take place in water
or mid-air, or limit the individual’s ability to recognise and self-treat hypoglycaemia. Those
involved in strenuous or water sports should have a ‘buddy’ able to offer assistance. These
activities include:
• Rock climbing.
• Flying.
• Abseiling.
• Car/motorbike racing.
• Cross country skiing.
• Swimming in open water or snorkelling.
People with insulin-treated diabetes are generally advised to avoid the following activities
unless special precautions to avoid hypoglycaemia are taken and a full understanding of the
possible dangers are appreciated:
• Hang-gliding (except in tandem).
• Scuba diving (The Australian Diabetes Society in 1994 produced a position paper
stating that type 1 diabetes is an ‘absolute contra-indication’ to Entry Level SCUBA
diving).5
Short-Term Effects
The normal physiological response to physical activity is to decrease plasma insulin levels
and increase plasma glucagon in order to increase hepatic glucose production and prevent
hypoglycaemia. These normal hormonal adaptations to exercise are essentially lost in
children and adolescents with type 1 diabetes. Hypoglycaemia during physical activity rarely
occurs in nondiabetic individuals. High insulin levels due to exogenous insulin
administration, can prevent the mobilisation of hepatic glucose, making hypoglycaemia more
likely in a patient with type 1 diabetes.3 Hypoglycaemia may occur during, immediately after
or many hours after physical activity. Therefore, it is recommended that:
2
• Blood glucose levels need to be measured before, during and after physical activity.
99
•
•
•
•
•
•
Physical activity may necessitate extra carbohydrate intake and insulin reduction.2 A
general recommendation is that 15 gm of easily absorbable carbohydrate or an extra
serving should be taken for every 30 minutes of moderate to intensive sport or physical
activity. Experience and blood glucose monitoring help determine the most appropriate
strategies as the requirements vary for each individual.
All children and adolescents participating in sport should have access to assistance
from a person aware of the management of hypoglycaemia during physical activity.
Extra carbohydrate should be consumed if blood glucose level is <7 mmol/L.2 Exercise
should be delayed if blood glucose is <3.5 mmol/L.
Special attention should be given to children and adolescents performing intensive
sports, especially those involving endurance training, due to the association with
delayed hypoglycaemic reactions which may occur in the middle of the night or before
breakfast the next day.
Advice should be sought from a dietitian for carbohydrate foods suitable for those
undertaking endurance sports.
Intensive physical activity needs to have appropriate reductions made in dosages of the
insulin acting during and for the following 12-24 hours after the physical activity. In
some cases decreasing insulin before physical activity reduces the need for extra food.
Those who are underinsulinised may experience an excessive release of counter-regulatory
hormones during physical activity. This may increase already high levels of glucose and
ketones and can even precipitate ketoacidosis.3 Therefore, it is recommended that children
with type 1 diabetes should avoid physical activity if blood glucose levels are >15 mmol/L
especially if ketosis is present.2
Long-term Effects
Regular physical activity in children and adolescents with type 1 diabetes can improve
aerobic capacity6-8 and muscle strength;7 however the reported effect of physical activity on
glycaemic control (measured by HbA1c) varies.
One small RCT (n=9) showed an improvement in HbA1c with regular sustained physical
activity compared with 30 minutes vigorous physical activity three times per week (HbA1c
11.3% versus 13.3%); however this group of patients was in very poor metabolic control.8
Another small study (n=12) found that the HbA1c in both ‘poorly’ (HbA1c >9%) and ‘well’
controlled (HbA1c <9%) diabetic patients was not affected by 12 weeks of supervised
training.6 During the ensuing 12 week period of unsupervised training, any improvement in
aerobic capacity decreased to pre-training levels suggesting that compliance with
unsupervised training was poor.6 In a third study of a 12 week physical activity program, the
HbA1c of subjects with type 1 diabetes was reduced (only in those with poor glycaemic
control) by 1% (p <.05).7
The Evidence
The evidence for the long term effects of physical activity in children and adolescents with
type 1 diabetes is listed in Evidence Table 8.1.6-8
• Regular physical activity in children and adolescents with type 1 diabetes can improve
aerobic capacity6-8 and muscle strength;7 however the reported effect of physical activity
on glycaemic control (measured by HbA1c) varies. (II, IV)
100
•
The role of physical activity in health promotion and disease prevention has been
emphasised by the World Health Organization.1(T) There are no published studies which
indicate that these benefits are changed by having type 1 diabetes.2(T)
• Physical activity should be considered part of diabetes management. Children and
adolescents with type 1 diabetes should be encouraged to participate in a variety of sport
and physical activity and not be limited in their choice of activity.4(C)
• Regular physical activity in children and adolescents with type 1 diabetes should be
encouraged as it can improve aerobic capacity6-8 and muscle strength;7 however the
reported effect of physical activity on glycaemic control (measured by HbA1c) varies.(II,IV)
• Activities should be approached with caution if they are solo in nature, take place in water
or mid-air, or limit the individual’s ability to recognise and self-treat hypoglycaemia and a
‘buddy’ is recommended.4(C)
2
• Blood glucose levels need to be measured before, during and after physical activity. (C)
• Physical activity may necessitate extra carbohydrate intake and insulin reduction.
Experience and blood glucose monitoring help determine the most appropriate strategies
as the requirements vary for each individual.2(C)
• All children and adolescents participating in sport should have access to assistance from a
person aware of the management of hypoglycaemia.(C)
• A general recommendation is that 15 gm of easily consumed and quickly absorbed
carbohydrate or an extra serving should be taken for every 30 minutes of moderate to
intensive sport or physical activity.(C)
2;9
• Extra carbohydrate should be consumed if blood glucose level is <7 mmol/L. (C)
• Strenuous physical activity should be avoided if blood glucose levels are >15 mmol/L
especially if ketones are present.9(C)
T = Technical Report
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
9.
WHO Technical Report Series. Diet, Nutrition and the Prevention of Chronic Disease. Report of a Joint WHO/FAO Expert
Consultation. 2003.
and Young). 2004.
American Diabetes Association: Physical Activity/Exercise and Diabetes Mellitus. Diabetes Care 26:73S-777, 2003
Australian Diabetes Society. ADS Position Statements: SCUBA Diving. Hazel J. 1994. Westmead, NSW.
Roberts L, Jones TW, Fournier PA: Exercise training and glycemic control in adolescents with poorly controlled type 1 diabetes
mellitus. Journal of Pediatric Endocrinology & Metabolism 15:621-627, 2002
Mosher PE, Nash MS, Perry AC, LaPerriere AR, Goldberg RB: Aerobic circuit exercise training: effect on adolescents with wellcontrolled insulin-dependent diabetes mellitus. Archives of Physical Medicine & Rehabilitation 79:652-657, 1998
Campaigne BN, Gilliam TB, Spencer ML, Lampman RM, Schork MA: Effects of a physical activity program on metabolic control
and cardiovascular fitness in children with insulin-dependent diabetes mellitus. Diabetes Care 7:57-62, 1984
101
The following guidelines for the management of diabetic ketoacidosis take into account the
conclusions of a consensus statement resulting from a workshop that took place in the United
Kingdom involving the European Society for Paediatric Endocrinology (ESPE) and the
Lawson Wilkins Pediatric Endocrine Society (LWPES). The Consensus statement was
developed with close partnership between the ESPE and LWPES and the International
Society for Pediatric and Adolescent Diabetes (ISPAD), all three organisations being
represented by members who participated in the writing process. The statement was also
endorsed by and contributed to by related organisations; the Juvenile Diabetes Research
Foundation International (JDRFI), the World Federation of Pediatric Intensive and Critical
Care Societies, the European Society for Pediatric Critical Care, the European Society of
Paediatric and Neonatal Intensive Care (ESPNIC) and the Australian Pediatric Endocrine
Group (APEG) were represented by invited participants.1
Definition and Aetiology
Diabetic ketoacidosis is a life-threatening disorder that is due to decreased effective
circulating insulin concentration,2 in association with insulin resistance3;4 and increased
production of counter-regulatory hormones such as glucagon, catecholamines, cortisol and
growth hormone.5-8
The hormonal changes cause:
• Increased hepatic and renal glucose production and impaired peripheral glucose
utilisation, leading to hyperglycaemia and hyperosmolality.
• Increased lipolysis and unrestrained production of ketoacids (betahydroxybutyrate and
acetoacetate),9 resulting in ketonaemia and eventual metabolic acidosis.
Hyperglycaemia leads to osmotic diuresis, loss of electrolytes and dehydration, which can
exacerbate the metabolic acidosis.10
The biochemical criteria for the diagnosis of diabetic ketoacidosis include:
• Hyperglycaemia, defined by a blood glucose (BG) level >11 mmol/L.
• Venous pH <7.3
• Bicarbonate <15 mmol/L.
Rarely, young or partially treated children and pregnant adolescents may present in diabetic
ketoacidosis with near-normal glucose values (‘euglycaemic ketoacidosis’).10
Diabetic ketoacidosis may be classified by the severity of the acidosis:
• Mild (venous pH 7.25 to 7.30, bicarbonate concentration 10-15 mmol/L).
• Moderate (pH 7.1 to 7.24, bicarbonate 5-10 mmol/L).
10
• Severe (pH <7.1, bicarbonate <5 mmol/L).
Diabetic ketoacidosis is usually associated with at least 5% dehydration, vomiting and/or
drowsiness.
Factors associated with diabetic ketoacidosis in children with newly diagnosed type 1
diabetes include younger age (those aged less than five years are at greatest risk),11 children
without a first degree relative with type 1 diabetes,12 and those from families of lower
socioeconomic status.2;11;13 High dose glucocorticoids,14 antipsychotics,16 diazoxide and
102
immunosuppressive drugs have been reported to precipitate diabetic ketoacidosis in
individuals not previously diagnosed with type 1 diabetes. Diabetic ketoacidosis has been
reported in at least 25% of children with newly diagnosed type 2 diabetes.17;18
The risk of diabetic ketoacidosis in established type 1 diabetes is increased in children and
young people with poor metabolic control or previous episodes of diabetic ketoacidosis.11;15
The most common precipitating factors in the development of diabetic ketoacidosis include
infection,10;19 often as a result of inadequate insulin therapy during intercurrent illness and
insulin omission.11;20-22 Adolescent girls,23-25 children with psychiatric disorders,25;26 such as
eating disorders, and those from families of lower socio-economic status are also at increased
risk.22;27 Diabetic ketoacidosis is rare in children whose insulin is administered by a
responsible adult.21 Furthermore, after medical and educational interventions, metabolic
control improved and diabetic ketoacidosis decreased.21
Diabetic ketoacidosis has been reported in association with continuous subcutaneous
insulin infusion (CSII), as inappropriate interruption of insulin pump therapy can precipitate
diabetic ketoacidosis.11;28;29 Recent studies, however, have failed to find an increased risk of
diabetic ketoacidosis in patients treated with CSII.30;31 Children and adolescents are advised
to have needles and syringes in reserve in case of insulin pump malfunction.
Epidemiology
The frequency of diabetic ketoacidosis ranges from 16%-80% of children newly diagnosed
with diabetes, depending on geographic location.13;32;33 Diabetic ketoacidosis is the leading
cause of morbidity and is the most common cause of diabetes-related deaths in children and
adolescents with type 1 diabetes.34 Mortality is predominantly due to cerebral oedema which
occurs in 0.3% to 1% of all episodes of diabetic ketoacidosis.35;36
The aetiology and pathophysiology of cerebral oedema are poorly understood. Factors
associated with cerebral oedema include:
35;37;39
• Newly diagnosed type 1 diabetes.
37;38;39
• Younger age.
39
• Longer duration of symptoms.
36
• Indices of greater severity of diabetic ketoacidosis, such as dehydration and acidosis.
• During treatment of diabetic ketoacidosis, a smaller rise in measured serum sodium
concentration.36;40-42
Specifically, elevated blood urea at presentation of diabetic ketoacidosis has been associated
with increased risk of cerebral oedema,36 which probably reflects greater dehydration. The
severity of acidosis correlates with risk of cerebral oedema43 and bicarbonate treatment for
correction of acidosis has also been associated with an increased risk of cerebral oedema.36;44
Furthermore, after adjusting for the degree of acidosis, more severe hypocapnia at
presentation of diabetic ketoacidosis has been associated with cerebral oedema in two
studies.36;45
In contrast, an association between volume or sodium content of intravenous fluids, and
risk of cerebral oedema has not been found.36;39;42;45;46 Therefore, the association between
sodium change and cerebral oedema may be a consequence of cerebral salt wasting rather
than excessive fluid administration. Neither degree of hyperglycaemia at presentation nor rate
of change in serum glucose during treatment of diabetic ketoacidosis have been associated
with an increased risk of cerebral oedema.36;45
103
Management
Whenever possible a specialist/consultant paediatrician with training and expertise in the
management of diabetic ketoacidosis should direct management. The child should also be
cared for in a unit that has:
• Experienced nursing staff trained in monitoring and management of diabetic
ketoacidosis.
• Clear written guidelines for managing diabetic ketoacidosis.
• Access to laboratories that can provide frequent and accurate measurement of
biochemical variables.
Children with signs of severe diabetic ketoacidosis (long duration of symptoms, circulatory
compromise, depressed level of consciousness) or those who may be at increased risk for
cerebral oedema (<5 years of age, new onset, high blood urea, low pCO2) should be
considered for immediate treatment in an intensive care unit47 (paediatric if available) or a
children’s ward specialising in diabetes care with equivalent resources and supervision.
It may be possible to manage children with ketosis and hyperglycaemia at home or in an
ambulatory health care setting (such as an emergency ward) if they are not vomiting. The
response to treatment should be evaluated frequently (2-4 hourly). If ketosis is not corrected
by oral hydration and subcutaneous insulin within 12 hours, the child should be re-evaluated
and the need for IV fluids, insulin and admission to hospital should be reviewed.48;73
Steps in the Assessment and Management of Diabetic Ketoacidosis
The following steps are involved in the management of diabetic ketoacidosis:
• Clinical assessment.
• Resuscitation.
• Investigation.
• Monitoring.
• Rehydration.
• Sodium replacement.
• Potassium replacement.
• Insulin treatment.
• Management of cerebral oedema if present.
• Management of the recovery phase.
104
Algorithm for the Management of Diabetic Ketoacidosis
IMMEDIATE ASSESSMENT
Clinical History
Polyuria, polydipsia
Weight loss (weigh patient)
Abdominal pain
Tiredness
Vomiting
Confusion
Clinical Assessment
Assess hydration, perfusion, BP, GCS
Deep sighing respiration (Kussmaul)
Smell of ketones
Lethargy/drowsiness ± vomiting
Investigations
Venous blood gas, FBC, electrolytes, urea,
creatinine, other investigations as indicated
Biochemical signs of DKA include:
• Ketonuria/ketonaemia
• Blood glucose level >11mol/L
• pH <7.25, Bicarb <15 mmol/L
CONFIRMED DIAGNOSIS OF
DIABETIC KETOACIDOSIS
Contact Senior Staff
Shock (reduced peripheral pulses)
Reduced conscious level
Coma
Resuscitation
Airway ± insert NG tube
Breathing (100% O2)
Circulation (Saline 0.9%
10-20 ml/kg over 1-2 hours
(may need to repeat until
circulation restored)
Dehydration >5% but not in shock
Clinically acidotic (hyperventilation)
Vomiting
IV Therapy
Calculate fluid requirements
Correct over 48 hours
Use Saline 0.9% as initial fluid
Monitor ECG for elevated T-waves
Add KCL 40 mmol per litre fluid
Mild DKA (pH 7.25 to 7.3)
Clinically well
Tolerating fluids orally
Therapy
Start with SC insulin
Continue oral hydration
No improvement
Low-dose continuous INSULIN
INFUSION
0.1unit/kg/hour
(consider 0.05 U/kg/h for young child)
Critical Observations
Hourly blood glucose level, RR, HR, BP
Hourly accurate fluid input & output (insert urinary catheter if
conscious state impaired)
Neurological status at least hourly
Electrolytes and blood gas 2-4 hourly after start of IV therapy
Monitor ECG for T-wave changes
Acidosis not improving
Re-evaluate
IV fluid calculations
Insulin delivery systems & dose
Need for additional resuscitation
Consider sepsis
When blood glucose < 15 mmol/L
or blood glucose falls > 5 mmol/hour
IV Therapy
Change to Saline 0.45% + Glucose 5%
Adjust insulin infusion (not <0.05 U/kg/h)
Adjust sodium infusion to promote an
increase in serum sodium
Improvement
Clinically well, tolerating oral fluids
Source: adapted from ISPAD guidelines
Transition to SC Insulin
Start SC Insulin then
Stop IV insulin 90 mins later
Signs of neurological deterioration
Headache, slowing of heart rate,
irritability, decreased conscious level,
incontinence, specific neurological
signs
Exclude Hypoglycaemia
Is it cerebral oedema?
Management
Give Mannitol 0.25-1.0 g/kg
Restrict IV fluids
Call senior staff
Move to Intensive Care
Consider cranial CT/MRI only after patient stabilised
105
Clinical Assessment
The diagnosis and clinical assessment of diabetic ketoacidosis should be confirmed with the
following:
• Characteristic history of polydipsia and polyuria, which may be absent in the young
child.
• Full physical examination, including weight (where possible), BP, assessment for
evidence of acidosis (hyperventilation), assessment of conscious level (Glasgow Coma
Score) and severity of dehydration.
5% (reduced skin turgor, dry mucous membranes, tachycardia, tachypnoea).
10% (capillary return 3 seconds or more, sunken eyes).
>10% (shock, poor peripheral pulses, hypotension, oliguria).
Note: Volume deficit is difficult to assess accurately in diabetic ketoacidosis,
particularly in the young child, and may be overestimated because of the subjective
criteria used.49 Shock with haemodynamic compromise is uncommon in childhood
diabetic ketoacidosis.
• Biochemical confirmation: glycosuria, ketonuria, capillary BG level (which may be
inaccurate in the setting of circulatory compromise and acidosis) and acid-base status.
Resuscitation
The following aspects need to be considered in the resuscitation of a child or adolescent with
diabetic ketoacidosis:
• Assess and maintain airway patency and breathing.
• In severely shocked patients give 100% oxygen by facial mask.
• If shocked initiate IV fluid administration and volume expansion immediately with an
isotonic solution (0.9% saline). The volume and rate of administration depends on
circulatory status; where necessary the volume is typically 10-20 ml/kg over 1-2 hours,
which may be repeated as required.
• Use crystalloid and not colloid. There are no data to support the use of colloids in
preference to crystalloids in the treatment of diabetic ketoacidosis.
• Insert a nasogastric tube in patients with impaired consciousness or recurrent vomiting
to prevent aspiration of gastric contents.
Investigation
The following urgent baseline laboratory measurements should be ordered:
• Blood glucose.
• Blood electrolytes (calculate corrected sodium) (see correction formula for sodium
replacement) and osmolality (calculate by 2 [Na+ + K+] + glucose).
• Venous pH and acid base status (arterial blood gas if signs of shock are present).
• Full blood count and haematocrit (the white blood cell count may be elevated due to
stress and cannot be interpreted as a sign of infection).
• Blood urea and creatinine (creatinine measurements may be spuriously raised by assay
interference from ketones).
• Urine microscopy and culture.
• Blood cultures and chest x-ray if indicated.
• Urinalysis for ketones (and/or blood ketones).
106
Monitoring
The management of diabetic ketoacidosis in childhood is dependent on careful clinical
observation of progress. Throughout treatment, hourly clinical observations, IV and oral
medication, fluids and electrolytes, and laboratory results must be documented.
Signs of severe diabetic ketoacidosis (long duration of symptoms, cardiovascular
compromise, depressed level of consciousness) or increased risk for cerebral oedema
(including <5 years of age, new onset) should prompt immediate consideration of treatment
in an intensive care unit (paediatric if available) or in a children’s ward specialising in
diabetes care with equivalent resources and supervision.47
Monitoring includes:
• Hourly heart rate, respiratory rate, blood pressure.
• 2nd to 4th hourly temperature.
• Hourly accurate fluid input and output. If the level of consciousness is impaired, a
urinary catheter may be necessary. Fluid balance should be reassessed regularly (at
least 2nd hourly) because continuing polyuria may worsen dehydration.
• Hourly or more frequent neurological observations for warning signs and symptoms of
cerebral oedema.
Headache.
Inappropriate slowing of heart rate.
Recurrence of vomiting.
Change in neurological status (restlessness, irritability, increased drowsiness,
incontinence) or specific neurological signs (such as cranial nerve palsies, pupillary
response).
Rising blood pressure, decreased oxygen saturation.
Note: it may be difficult clinically to discriminate cerebral oedema from other causes of
altered mental status.
• Hourly capillary BG level measurement. Laboratory confirmation with venous glucose
should be performed every 2 to 4 hours because capillary methods may be inaccurate in
the presence of poor peripheral circulation and acidosis.
• Laboratory investigations: 2 to 4 hourly electrolytes, urea, haematocrit, venous BG
level and blood gases. In severe diabetic ketoacidosis it may be necessary to monitor
electrolytes hourly.
• In severe diabetic ketoacidosis, ECG monitoring may be helpful to assess T-waves for
evidence of hyperkalaemia or hypokalaemia.
• Urinalysis for ketones until negative.
Rehydration
Diabetic ketoacidosis is characterised by loss of water and electrolytes. The high effective
osmolality of the extracellular fluid (ECF) compartment results in a shift of water from the
intracellular fluid compartment (ICF) to the ECF. Elevated serum urea nitrogen and
haematocrit may be useful markers of severe ECF contraction. Dehydration is associated with
a reduction in glomerular filtration rate (GFR), leading to reduced glucose and ketone
clearance, which potentiate diabetic ketoacidosis.
Administration of IV fluid prior to insulin results in substantial falls in blood glucose,
because the resultant increase in GFR leads to increased urinary glucose excretion.50;51
The aims of fluid and sodium replacement therapy in diabetic ketoacidosis are:
107
•
•
•
•
Restoration of circulating volume.
Replacement of sodium and water deficits over at least 36-48 hours.
Restoration of GFR with enhanced clearance of glucose and ketones from the blood.
Avoidance of cerebral oedema, which may be caused by fluid shifts from the ECF to
the ICF compartment.
Following initial resuscitation, subsequent fluid management should be with 0.9% saline. If
hypernatraemia is present consider the use of 0.45% saline.
• As the severity of dehydration is difficult to determine and may be overestimated, daily
fluid infusion rates should rarely exceed 1.5-2 times the usual daily requirement based
on age, weight, or body surface area.
• IV or oral fluids that were given before the initiation of hospital management should be
included in calculations of deficit and replacement. Urinary losses should not be added
to the initial calculation of replacement fluids.
• The patient should remain ‘nil by mouth’ except for ice to suck.
• Calculation of effective osmolality may be useful to guide ongoing fluid and electrolyte
therapy.
Sodium Replacement
Measurement of serum sodium is an unreliable measure of the degree of ECF contraction and
may be depressed due to the dilutional effect of hyperglycaemia and fluid shift from the ICF
to the ECF.
Corrected sodium concentration can be calculated as:52
• corrected sodium = sodium + [2 x (glucose - 5.5)] / 5.5 (all values in mmol/L)
The calculation can be simplified to 2 mmol/L of sodium to be added for every 5.5 mmol/L
of glucose above 5.5 mmol/L.
Normal saline is used as the initial rehydration fluid.
Effective osmolality (2 [Na+ + K+] + glucose) at the time of presentation is frequently in the
range of 300-350 mOsm/L. If the corrected sodium is greater than 150 mmol/L, a
hypernatraemic as well as an independent glucose hyperosmolar state exists and correction of
dehydration and electrolyte imbalances should be over 48-72 hours. Normal Saline with 40
mmol/L KCl has an osmolality of 390 mOsm/L, which may exacerbate the hyperosmolar
state. The continued use of large amounts of 0.9% Saline has also been associated with the
development of hyperchloraemic metabolic acidosis.53
The use of hypotonic fluids, however, is associated with greater rises in intracranial
pressure compared to isotonic fluids. Therefore, the use of solutions with salt content less
than 0.45% NaCl, which contain a large amount of electrolyte free water, is likely to lead to a
rapid osmolar change, movement of fluid into the ICF compartment and may increase the risk
of cerebral oedema. The failure of the serum sodium to rise or development of hyponatraemia
during IV fluid administration has been shown to precede cerebral oedema.41;42
Potassium Replacement
Diabetic ketoacidosis in adults is associated with total body potassium deficits of
approximately 3-6 mmol/kg, but data are lacking in children. Hypertonicity, insulin
deficiency, and buffering of hydrogen ions within the cell lead to potassium loss. Serum
potassium may be reduced, normal or elevated at the time of presentation. Hypokalaemia
108
may be related to prolonged duration of disease, whereas hyperkalaemia is due to reduced
renal function. Administration of insulin and the correction of acidosis will drive potassium
back into the cells, decreasing serum levels.
The following issues need to be considered in potassium replacement:
• Potassium should be added after restoring normal circulation, concurrent with starting
insulin therapy.
• Replacement therapy should be based on serum potassium measurements.
If the patient is anuric (after passage of a catheter) or hyperkalaemic, defer
potassium replacement until urine output is documented and electrolytes are
available.
If the patient is hypokalaemic, start potassium replacement immediately.
• Commence replacement at a dose of 5 mmol/kg/day (40 mmol/L IV fluid).
• Do not exceed a maximal potassium infusion rate of 0.5 mmol/kg/hour without
consultation/cardiac monitoring.
• Potassium replacement should continue throughout intravenous fluid therapy.
• Potassium phosphate salts may be used as an alternative or in combination with
potassium chloride/acetate to avoid hyperchloraemia; however administration of
phosphate may induce hypocalcaemia54;55 and prospective studies have failed to show
significant clinical benefit from phosphate replacement.56-58
Bicarbonate Replacement
Severe acidosis is reversible by fluid and insulin replacement. Insulin administration arrests
further synthesis of ketoacids and allows excess ketoacids to be metabolised. The metabolism
of keto-anion results in the regeneration of bicarbonate and correction of acidaemia.
Furthermore, treatment of hypovolaemia improves poor tissue perfusion and renal function,
leading to excretion of organic acids and reversal of lactic acidosis, which may account for up
to 25% of the acidaemia.
Prospective controlled trials of sodium bicarbonate in small numbers of children and
adults with diabetic ketoacidosis have failed to demonstrate a clinical benefit or harm.36;59;60
Bicarbonate therapy may cause paradoxical CNS acidosis and rapid correction of acidosis
may cause hypokalaemia, accentuate sodium load and contribute to serum hypertonicity.
Bicarbonate therapy may also increase hepatic ketone production, thus slowing the rate of
recovery from the ketosis.61 No prospective randomised studies of patients with severe
diabetic ketoacidosis (pH <6.9) have been reported.
Some patients may benefit from cautious bicarbonate therapy, such as those with severe
acidaemia (pH <6.9 ± serum bicarbonate <5 mmol/L), which causes decreased cardiac
contractility, peripheral vasodilatation and impaired tissue perfusion, and patients with
potentially life-threatening hyperkalaemia. If bicarbonate is given, it should be administered
at a dose of 1-2 mmol/kg by an intravenous infusion over 60 minutes. Cardiac monitoring
should be performed in these patients due to the risk of inducing hypokalaemia.
Insulin
Rehydration alone will decrease the BG level to some extent; however insulin therapy is
required to normalise the BG level and to suppress lipolysis and ketogenesis. Insulin therapy
offsets insulin resistance and inhibits lipolysis and ketogenesis; causing suppression of
glucose production and stimulated peripheral glucose uptake. The resolution of acidaemia
usually takes longer than normalisation of blood glucose concentrations. Although different
109
routes (SC, IM, IV) and doses have been used, there is considerable evidence to support the
use of ‘low dose’ intravenous insulin.63-67
Outline of insulin treatment:
• Insulin dose: 0.1 units/kg/hour by IV infusion. Consider 0.05u/kg/hr in the younger
child.
• BG level should fall by approximately 4-5 mmol/L per hour, but initial rehydration
alone will cause the BG level to fall, so a greater drop in BG level can be accepted in
the first few hours of treatment.
• The dose of insulin should remain at 0.1 U/kg/hour at least until resolution of
ketoacidosis (pH >7.30, HCO3 >15 mmol/L and/or closure of anion gap).
• When the BG level falls to 15 mmol/L, glucose should be added to the IV fluid to
prevent an unduly rapid decrease in plasma glucose concentration and possible
development of hypoglycaemia. A solution of 0.45% saline and 5% dextrose (prepared
by adding 25 ml of 50% dextrose to 500 ml of 0.45% saline and 2.5% dextrose) is
commonly used.
• In cases of hyponatraemia, IV fluid with a higher sodium content (for example, Normal
Saline) may be used with dextrose added.
• The insulin infusion rate and/or the dextrose infusion rate should then be adjusted to
keep the BG level between 5-10 mmol/L.
• The insulin infusion rate should only be decreased if the BG level remains below the
target range despite dextrose supplementation.
• Do not stop insulin infusion or decrease below 0.05 units/kg/hour because continuous
supplies of both insulin and glucose substrate are required to promote anabolism and
reduce ketosis.
• If IV fluids are required after 24 hours 0.45% saline adjusted to 5% dextrose may be
used.
• If biochemical parameters of ketoacidosis (pH, anion gap) do not improve, reassess the
patient, review insulin therapy, and consider other possible causes of impaired response
to insulin (for example infection, errors in insulin preparation, adhesion of insulin to
tubing with very dilute solutions).
• In circumstances where IV administration is not possible, IM or SC insulin
administration has been used effectively and has been demonstrated to be safe.68 It
should be noted that poor perfusion will impair insulin absorption.69
The insulin infusion can be prepared by adding 50 units of short-acting or rapid-acting insulin
to 500 ml of 0.9% saline, resulting in a solution containing 1 unit of insulin per 10 ml. The
infusion may be run as a sideline with the rehydrating fluid, providing a volumetric pump is
used. Some intensive care units prefer to use a more concentrated solution of insulin and a
step syringe pump. If a volumetric pump is not available, a separate IV site may be required
for low infusion rates. The insulin infusion and the giving set should be changed every 24
hours, due to the potential for insulin to denature. The insulin infusion must be clearly
labelled so that confusion with the rehydrating solution does not occur.
Management of Cerebral Oedema
Treatment should be initiated as soon as the condition is suspected. Management should
involve:
• Reduction in the rate of fluid administration.
110
•
Intravenous mannitol should be given (0.25-1.0g/kg over 20 mins) in patients with
signs of cerebral oedema before impending respiratory failure. Although mannitol has
been shown to have possible beneficial effects in case reports, there has been no
definite beneficial or detrimental effect in epidemiological studies.37;70 Timing of
administration (delayed administration being less effective) may alter the response.
71
• Repeat mannitol administration in 2 hours if there is no initial response.
• Hypertonic saline (3%) 5-10 ml/kg over 30 mins may be an alternative to mannitol.
Intubation and ventilation may be necessary, but aggressive hyperventilation has been
associated with poor outcome in retrospective studies of diabetic ketoacidosis-related
cerebral oedema.36
• The patient should be transferred to an intensive care facility and a neurological
assessment and MRI or CT scan arranged.
Management of the Recovery Phase
Recovery management involves:
• Transition from IV fluids and ‘nil by mouth’ to oral fluids.
• Transition from continuous insulin infusion to subcutaneous insulin.
Oral fluids
• These should be introduced when the patient is metabolically stable (BG level <12
mmol/L, pH >7.30 and HCO3 >15 mmol/L). Low joule or low calorie fluids may be
given by mouth as tolerated and should be included in the fluid balance calculations.
Covering snacks and meals on intravenous insulin infusion
• It is useful to maintain the insulin infusion until the child or adolescent has had at least
one meal.
• For snacks the basal infusion rate is doubled at the commencement of the snack and
continued for the duration of the snack and 30 minutes afterwards before returning to
the basal rate.
• For main meals the basal infusion rate should be doubled at the commencement of the
meal and continued at this rate for the duration of the meal and for 60 minutes after the
meal. The infusion rate can then be returned to the basal rate.
• The insulin infusion can be discontinued when the patient is alert and metabolically
stable and when eating has been established.
Transition from intravenous to subcutaneous insulin
• The most convenient time to change to subcutaneous insulin is just before a mealtime.
The subcutaneous insulin should be given 30 minutes before the meal (or immediately
if rapid-acting insulin analogues are used). The insulin infusion should be continued
throughout the meal for a total of 30-90 minutes after the subcutaneous insulin injection
depending on the type of insulin used. The half-life of intravenous insulin is only 4.5
minutes; therefore it is important that the subcutaneous insulin is given before the
infusion is ceased.
• Short-acting insulin should be given 4 to 6 hourly, however the dose needs to be
individualised on the basis of serial blood glucose levels.
• The total daily dose required is at least 1 units/kg body weight/day, however this may
need to be adjusted on the basis of previous insulin dosages.
• Frequent monitoring in the post diabetic ketoacidosis interval is required to avoid
hypoglycaemia.62
111
•
Various regimens may be used:
The use of intermediate and short/rapid-acting insulin as a bd, tds or basal bolus
regimen will depend on the patient’s age and local practices. Typically for a bd
regimen the total insulin dose is approximately 1 unit per kg per day with _ given
before breakfast and _ before the evening meal, the ratio being _ intermediateacting insulin and _ short/rapid-acting (for further details, see Chapter 5).
The Evidence
The evidence for the definition and aetiology of diabetic ketoacidosis is listed in Evidence
Table 9.1.
• Diabetic ketoacidosis is due to decreased effective circulatory insulin concentration in
association with insulin resistance and increased production of counter-regulatory
hormones.3-8(III-2)
The evidence for the frequency of diabetic ketoacidosis is listed in Evidence Table 9.1.
• The frequency of diabetic ketoacidosis ranges from 16 to 80% in children newly diagnosed
with diabetes, depending on geographic location.13;32;33(IV)
The evidence for the factors associated with diabetic ketoacidosis is listed in Evidence Table
9.1.
• Factors associated with diabetic ketoacidosis in children with newly diagnosed type 1
diabetes include younger age (those aged less than five years are at greatest risk),11 children
without a first degree relative with type 1 diabetes,12 and those from families of lower
socioeconomic status.2;11;13(IV)
• Diabetic ketoacidosis has been reported in at least 25% of children with newly diagnosed
type 2 diabetes.17;18(IV)
The evidence for the most common precipitating factors of diabetic ketoacidosis in
established type 1 diabetes is listed in Evidence Table 9.1.
• The risk of diabetic ketoacidosis in established type 1 diabetes is increased in children and
young people with poor metabolic control or previous episodes of diabetic
ketoacidosis.11;15 The most common precipitating factors in the development of diabetic
ketoacidosis include infection, often as a result of inadequate insulin therapy during
intercurrent illness and insulin omission. 10;11;19;20-22 Adolescent girls,23-25 children with
psychiatric disorders,25;26 such as eating disorders, and those from families of lower socioeconomic status are also at increased risk.22;27(IV)
• Diabetic ketoacidosis has been reported in early studies in association with continuous
subcutaneous insulin infusion (CSII), as inappropriate interruption of insulin pump therapy
can precipitate diabetic ketoacidosis.11;28;29 However, more recent studies have not
documented an increased risk of diabetic ketoacidosis in patients treated with CSII.30;31(III2)
The evidence for mortality in diabetic ketoacidosis and risk factors for cerebral oedema is
listed in Evidence Table 9.1.
diabetes.10;11;22;34(IV)
• The greatest risk of mortality from diabetic ketoacidosis is from cerebral
oedema.10;11;22;35;36(IV)
• Although poorly understood, the risk factors for cerebral oedema in diabetic ketoacidosis
include presentation with new onset type 1 diabetes,35;37;39 younger age,37;38;39 elevated
serum urea nitrogen and/or severity of dehydration at presentation, severity of acidosis,36;43
greater hypocapnia at presentation (after adjusting for degree of acidosis), an attenuated
112
rise in serum sodium during treatment for diabetic ketoacidosis36;40-42; bicarbonate
treatment to correct acidosis has also been associated with cerebral oedema.36;44 (III/IV)
Most studies have not found an association between cerebral oedema and degree of
hyperglycaemia at presentation of diabetic ketoacidosis, rate of change of serum glucose
during diabetic ketoacidosis treatment or volume or sodium content of intravenous fluids
have.36;45;46(III/IV)
The evidence for predictors of need for admission to hospital or ICU for management of
diabetic ketoacidosis or ketosis with hyperglycaemia is listed in Evidence Table 9.1.
• Children with signs of severe diabetic ketoacidosis (long duration of symptoms,
circulatory compromise, depressed level of consciousness) or those who may be at
increased risk for cerebral oedema (<5 years of age, new onset, high blood urea, low
pCO2) should be considered for immediate treatment in an intensive care unit47 (paediatric
if available) or a children’s ward specialising in diabetes care with equivalent resources
and supervision.(IV)
• It may be possible to manage children with ketosis and hyperglycaemia at home or in an
ambulatory health care setting (such as an emergency ward) if they are not
vomiting.48;73(IV)
The evidence for difficulties in assessing dehydration in diabetic ketoacidosis is listed in
Evidence Table 9.1.
• Volume deficit is difficult to assess accurately in diabetic ketoacidosis, particularly in the
young child, and may be overestimated because of the subjective criteria used.49(III-3)
The evidence for issues in the management of diabetic ketoacidosis is listed in Evidence
Table 9.1.
53
• Hyperchloraemic acidosis and Sodium replacement. (III-2)
• Potassium phosphate salts may be used as an alternative or in combination with potassium
chloride/acetate to avoid hyperchloraemia; however administration of phosphate may
induce hypocalcaemia54;55(IV) and prospective studies have failed to show significant
clinical benefit from phosphate replacement.56-58(III-1)
• Prospective controlled trials of sodium bicarbonate in small numbers of children and
adults with diabetic ketoacidosis have failed to demonstrate a clinical benefit or harm.
36;59;60
Furthermore, bicarbonate therapy may cause paradoxical CNS acidosis and rapid
correction of acidosis may cause hypokalaemia, accentuate sodium load and contribute to
serum hypertonicity. Bicarbonate therapy may also increase hepatic ketone production,
thus slowing the rate of recovery from the ketosis.61(III-1)
• Although different routes (SC, IM, IV) and doses have been used, there is considerable
evidence to support the use of ‘low dose’ intravenous insulin.63-67(II)
• In circumstances where IV administration is not possible, IM or SC insulin administration
has been used effectively and has been demonstrated to be safe.68 It should be noted that
poor perfusion will impair insulin absorption.69(II)
The evidence for the management of cerebral oedema in diabetic ketoacidosis is listed in
Evidence Table 9.1.
• Intravenous mannitol should be given (0.25-1.0g/kg over 20 mins) in patients with signs of
cerebral oedema before impending respiratory failure. Although mannitol has been shown
to have possible beneficial effects in case reports, there has been no definite beneficial or
detrimental effect in epidemiological studies.37;70(IV)
71
• Repeat mannitol administration in 2 hours if there is no initial response. (IV)
113
•
Hypertonic saline (3%) 5-10 ml/kg over 30 mins may be an alternative to mannitol.
Intubation and ventilation may be necessary, but aggressive hyperventilation has been
associated with poor outcome in retrospective studies of diabetic ketoacidosis-related
cerebral oedema.36(III-3)
• The guidelines for the management of diabetic ketoacidosis take into account the
conclusions of a consensus statement resulting from a workshop that took place in the
United Kingdom involving the European Society for Paediatric Endocrinology (ESPE)
and the Lawson Wilkins Pediatric Endocrine Society (LWPES). The Consensus statement
was developed with close partnership between the ESPE and LWPES and the International
Society for Pediatric and Adolescent Diabetes (ISPAD), all three organisations being
represented by members who participated in the writing process. The statement was also
endorsed by and contributed to by related organisations; the Juvenile Diabetes Research
Foundation International (JDRFI), the World Federation of Pediatric Intensive and Critical
Care Societies, the European Society for Pediatric Critical Care, the European Society of
Paediatric and Neonatal Intensive Care (ESPNIC) and the Australian Pediatric Endocrine
Group (APEG).1
• The American Diabetes Association has produced a position statement on hyperglycaemic
crises in patients with diabetes mellitus.10
• The guidelines for the management of diabetic ketoacidosis should take into account the
conclusions of a consensus statement resulting from a workshop that took place in the
United Kingdom in June 2003 involving the European Society for Paediatric
Endocrinology (ESPE), the Lawson Wilkins Pediatric Endocrine Society (LWPES) and
other societies including the Australasian Paediatric Endocrine group (APEG).1(C)
• The most common precipitating factors in the development of diabetic ketoacidosis
include infection, often as a result of inadequate insulin therapy during intercurrent illness
and insulin omission.10;11;19;20-22(IV)
diabetes.10;11;22;34(IV)
• The greatest risk of mortality from diabetic ketoacidosis is from cerebral
oedema.10;11;22;35;36(IV)
• Although poorly understood, the risk factors for cerebral oedema in diabetic ketoacidosis
include presentation with new onset type 1 diabetes,35;37;39 younger age,37;38;39 elevated
serum urea nitrogen and/or severity of dehydration at presentation, severity of acidosis,36;43
greater hypocapnia at presentation (after adjusting for degree of acidosis), an attenuated
rise in serum sodium during treatment for diabetic ketoacidosis36;40-42; bicarbonate
treatment to correct acidosis has also been associated with cerebral oedema.36;44(III,IV)
• Immediate assessment for diabetic ketoacidosis should consist of clinical history,
assessment and biochemical confirmation (see algorithm).72(C)
• ‘Low dose’ intravenous insulin is recommended for the treatment of moderate to severe
diabetic ketoacidosis. 1(C)
• A specialist/consultant paediatrician with training and expertise in the management of
diabetic ketoacidosis should direct management.1(C)
• The child should be cared for in a unit that has experienced nursing staff trained in
monitoring and management of diabetic ketoacidosis, clear written guidelines for
114
managing diabetic ketoacidosis and access to laboratories that can provide frequent and
accurate measurement of biochemical variables.1(C)
• Children with ketosis and hyperglycaemia, but who are not vomiting, may be managed at
home or in an ambulatory care setting (such as an emergency ward). 48;73(IV)
• Children with signs of severe diabetic ketoacidosis or those who may be at increased risk
for cerebral oedema should be considered for immediate treatment in an intensive care unit
(paediatric if possible) or a children’s ward specialising in diabetes care.(C)
• The management of cerebral oedema in diabetic ketoacidosis is a medical emergency and
treatment (fluid restriction, mannitol, neurological assessment) should be initiated in an
intensive care facility as soon as the condition is suspected.37;70(IV)
III-1 = Evidence from well-designed pseudo-randomised controlled trials (alternate allocation or some other method).
III-2 = Evidence from comparative studies with concurrent controls and allocation, non-randomised (cohort studies), casecontrol studies, or interrupted time series with a control group
III-3 = Evidence from comparative studies with historical control, two or more single-arm studies, or interrupted time series
without a parallel control group
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complications in children with type 1 diabetes. Journal of the American Medical Association 287:2511-2518, 2002
Liss DS, Waller DA, Kennard BD, McIntire D, Capra P, Stephens J: Psychiatric illness and family support in children and
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Bello FA, Sotos JF: Cerebral oedema in diabetic ketoacidosis in children. Lancet 336:64, 1990
Duck SC, Wyatt DT: Factors associated with brain herniation in the treatment of diabetic ketoacidosis. Journal of Pediatrics
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Waldhausl W, Kleinberger G, Korn A, Dudczak R, Bratusch-Marrain P, Nowotny P: Severe hyperglycemia: effects of rehydration
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Adrogue HJ, Wilson H, Boyd AE, III, Suki WN, Eknoyan G: Plasma acid-base patterns in diabetic ketoacidosis. New England
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therapy. American Journal of Medicine 67:897-900, 1979
Zipf WB, Bacon GE, Spencer ML, Kelch RP, Hopwood NJ, Hawker CD: Hypocalcemia, hypomagnesemia, and transient
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replacement on erythrocyte 2,3-diphosphoglycerate and haemoglobin-oxygen affinity in diabetic ketoacidosis. Diabetologia 15:381385, 1978
Wilson HK, Keuer SP, Lea AS, Boyd AE, III, Eknoyan G: Phosphate therapy in diabetic ketoacidosis. Annuls of Internal Medicine
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Morris LR, Murphy MB, Kitabchi AE: Bicarbonate therapy in severe diabetic ketoacidosis. Annals of Internal Medicine 105:836840, 1986
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Baum JD, Jenkins P, Aynsley-Green A: Immediate metabolic response to a low dose of insulin in children presenting with diabetes.
Burghen GA, Etteldorf JN, Fisher JN, Kitabchi AQ: Comparison of high-dose and low-dose insulin by continuous intravenous
infusion in the treatment of diabetic ketoacidosis in children. Diabetes Care 3:15-20, 1980
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for Diabetic Ketoacidosis (Abstract). Diabetes 52:A139, 2003
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ketoacidosis. Lancet 2:1221-1224, 1975
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Pediatric Diabetes 2(4):191-4, 2001
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Care 12:347-351, 1996
117
Surgery on children with diabetes should only be undertaken in hospitals with dedicated
paediatric facilities for the care of children with diabetes and expert staff (medical,
anaesthetic, surgical and nursing).
Children with diabetes requiring a surgical procedure need insulin, even if fasting, to avoid
ketoacidosis. They may have increased insulin requirements peri-operatively due to
physiological stress and increased counter-regulatory hormones.1-3
When fasting before an anaesthetic an intravenous glucose infusion should be commenced
to prevent hypoglycaemia. Paediatric patients particularly those under the age of 5 years old
may be prone to hypoglycaemia during anaesthesia and surgery.4;5
Emergency Surgery
Unless it is absolutely clinically indicated, emergency surgery should be delayed in any
patient with ketoacidosis until diabetes control has improved and the diabetes stabilised.
Diabetic ketoacidosis may by itself cause an acute abdomen, which resolves with treatment of
the ketoacidosis.
Elective Surgery
Elective surgery should only be performed in a child or adolescent whose diabetes is under
good control.
If glycaemic control is uncertain or poor:
• The child or adolescent should enter hospital beforehand for assessment and
stabilisation of metabolic control.
• If control remains poor, surgery should be cancelled and re-booked.
Scheduling of Surgery
Operations should be scheduled early in the morning if possible. If surgery cannot be
scheduled for the morning, the patient with diabetes should be first on the afternoon list. This
will allow post-operative stabilisation during the day shift.
Maintaining Metabolic Control
Any patient with diabetes who is undergoing prolonged fasting requires:
• Continuous intravenous glucose.
• Hourly blood glucose monitoring in order to maintain blood glucose levels of 5-10
mmol/L.
• Adequate insulin replacement.
The management of diabetes during surgery or procedures that require fasting is complex and
exacting. There are different approaches and each case must be judged on its own merits. The
suggested protocols below have been shown to be efficacious but do not imply that other
protocols when carried out by physicians expert in the care of childhood and adolescent
diabetes cannot be used or are in any way less efficacious.
In children and adolescents with type 1 diabetes the optimal method of maintaining metabolic
control during major surgery or prolonged post-operative fasting is by an insulin infusion,3
118
which should be started in association with a maintenance saline/dextrose infusion when
fasting commences.
Blood glucose levels must be done hourly whilst on an insulin infusion. Other tests such as
electrolytes, blood gases and additional parameters will be determined by the underlying
clinical condition.
Intravenous Fluids
Intravenous fluid should commence at maintenance rates (see Table 9.1) when fasting begins.
The intravenous fluids should contain 5 percent dextrose (50 gm/L) initially. This can be
made by adding 25 ml of 50% dextrose to 500 ml of N/2 Saline + 2.5% dextrose, or by
adding 12.5 ml of 50% dextrose to 500 ml of N/4 + 3.75% dextrose. The glucose
concentration of the fluids can be increased if required. An alternative fluid schedule, which
does not vary with age, is to use 1500 ml/m2/24 hours.
Table 10.1: Maintenance Fluid Volume for Different Age Groups6
Age Group
ml/kg/day
Up to 9 months
120-140
12 months
90-100
2 years
80-90
4 years
70-80
8 years
60-70
12 years
50-60
Management of Short or Minor Procedures Involving Sedation or Anaesthesia
Patients on twice or three times daily insulin regimens
Procedure first on morning list
For short procedures involving sedation or anaesthesia, it may be possible to simplify the
management of the diabetes by strategies such as:
Option 1:
Arrange for the procedure to be performed at 8 am and delaying the morning insulin
(and giving a reduced dose) until food is allowed (providing food is tolerated before 10
am).
Hourly monitoring of the blood glucose levels is still required.
Intravenous glucose will usually be required but may not be required if the procedure
is short and the blood glucose is maintained.
If food is not tolerated by 10 am, short/rapid-acting insulin will need to be started by
infusion or subcutaneous injections, in addition to the glucose infusion and frequent
monitoring.
Option 2:
Give a reduced morning insulin dose at about 7am (50-60% of the usual intermediate
insulin dose, no short/rapid-acting unless blood glucose level is high).6
Commence IV fluids at the same time (N/2 Saline + 5% dextrose, or N/4 + 5%
dextrose).
Perform hourly blood glucose readings and increase glucose concentration of IV fluids
to 7.5% or 10% if required.6
Extra mid-morning short/rapid-acting insulin may be given if required (10-25% of total
daily dose).6
119
Cease IV fluids once oral intake resumes. The usual doses of evening insulin can be
given if eating normally.6
Procedures first on afternoon list
If breakfast is not allowed follow the advice below for ‘major surgery where oral intake
is not possible for prolonged period’.
If breakfast is allowed give a reduced morning insulin dose prior to breakfast (30-40%
of usual intermediate-acting insulin and 50% of usual short/rapid-acting insulin,
depending on BG level).
Commence IV fluids 2 hours after breakfast (N/2 Saline + 5% dextrose, or N/4 + 5%
dextrose) at maintenance rates.
daily dose).6
Post-operatively, IV fluids can be ceased once oral intake resumes and additional doses
of short/rapid-acting insulin given if required.
The usual dose of evening insulin can be given if eating normally. Otherwise a reduced
dose should be given.6
Patients on basal-bolus insulin regimens
Procedures first on morning list
Consider the need for reduction (by 20-30%) of evening intermediate acting insulin if
there is a pattern of low blood glucoses in the morning.6
At 7am give 40-50% of the usual short/rapid-acting insulin and commence IV fluids
(containing 5% dextrose).6
daily dose).6
6
Usually resume normal food and insulin from lunch.
Procedures first on afternoon list
6
The patient is usually allowed breakfast.
6
At 7am give 50-60% of the usual short/rapid-acting insulin.
Commence IV fluids (containing 5% dextrose) at maintenance rates 2 hours after
breakfast.6
6
At 12noon give about 10% of the total daily dose of short/rapid-acting insulin.
Postoperatively, additional short/rapid-acting insulin may be required (usually 10% of
the total daily dose as needed 4-hourly),6 until normal eating is resumed.
6
Give the usual insulin and food at dinner and supper.
Patients on insulin pumps
The diabetes team will determine the approach depending on the individual patient and
procedure
Minor procedures: The pump can be continued at the basal rate, keeping glucose
infusion to a minimum. Monitor blood glucose levels hourly. Correction doses can be
given preoperatively and postoperatively as needed and carbohydrate boluses when the
120
patient is ready to eat. Alternatively the pump can be discontinued preoperatively and a
basal-bolus regimen instituted with adjustment as above.6
Major procedures: The subcutaneous insulin pump is discontinued and an IV insulin
infusion used.6
Major Surgery or Surgery where Oral Intake is not Possible for a Prolonged Period
•
Commence insulin infusion (see below) and intravenous fluids (containing 5%
dextrose) at maintenance rate.
• Hourly BG levels must be done while on an insulin infusion.
• Maintain BG level between 5-10 mmol/L by adjusting the rate of the insulin infusion
by 10% increments as required.6
Insulin Infusion Rates
Short-acting insulin should be administered as a separate intravenous infusion and diluted in
0.9 percent Saline solution (50 units of insulin in 500 ml of 0.9 percent Saline - equivalent to
1 unit of insulin per 10 ml Saline). The insulin infusion should be run through a volumetric
pump at an initial maintenance rate of 0.02 unit/kg/hr in a line separate from the hydration
fluid.6 Another protocol is to infuse the insulin at a rate of 0.15 unit/gram of glucose in the
maintenance fluids per hour.6 However, whatever the protocol used, the insulin dosage must
be adjusted according to individual requirements.
The blood glucose levels are maintained between 5-10 mmol/L by adjusting the rate of the
insulin infusion by increments of 10 percent.
The insulin infusion therapy is continued until oral food intake has been established and
subcutaneous insulin therapy is possible. The subcutaneous insulin should be given 30
minutes before the meal (or immediately if rapid-acting insulin analogues are used). The
insulin infusion should be continued throughout the meal for a total of 30-90 minutes after
the subcutaneous insulin injection depending on the type of insulin used.6
The Evidence
The evidence for the management of surgery and fasting in children and adolescents with
• Children and adolescents with type 1 diabetes have increased insulin requirements perioperatively.3(III-3)
• In children and adolescents with type 1 diabetes peri-operative management with an
insulin infusion results in better blood glucose control than subcutaneous insulin
injection.3(III-3)
Additional Consensus Statements used to formulate the recommendations and principles of
clinical practice are listed in Evidence Table 10.2.
• Surgery on children with diabetes should only be undertaken in hospitals with dedicated
paediatric facilities for the care of children with diabetes and expert staff (medical,
anaesthetic, surgical and nursing).7;8(C)
• When fasting before an anaesthetic an intravenous glucose infusion should be commenced
to prevent hypoglycaemia.7;8(C)
121
•
Children with type 1 diabetes requiring a surgical procedure should receive insulin, even if
fasting, to avoid ketoacidosis. There may be increased insulin requirements perioperatively due to physiological stress and increased counter-regulatory hormones.3(III-3)
• In children and adolescents with type 1 diabetes the optimal method of maintaining
metabolic control during major surgery or prolonged post-operative fasting is by an insulin
infusion.3(III-3)
III-3 = Evidence obtained from comparative studies with historical control, two or more single arm studies, or interrupted
time series without a parallel control group
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
Raucoules-Aime M, Roussel LJ, Rossi D, Gastaud P, Dolisi C, Grimaud D: Effect of severity of surgery on metabolic control and
insulin requirements in insulin-dependent diabetic patients. BJA: British Journal of Anaesthesia 74:231-233, 1995
Thomas DJ, Platt HS, Alberti KG: Insulin-dependent diabetes during the peri-operative period. An assessment of continuous
glucose-insulin-potassium infusion, and traditional treatment. Anaesthesia 39:629-637, 1984
Kaufman FR, Devgan S, Roe TF, Costin G: Perioperative management with prolonged intravenous insulin infusion versus
subcutaneous insulin in children with type I diabetes mellitus. Journal of Diabetes & its Complications 10:6-11, 1996
Kirschner RM: Diabetes in pediatric ambulatory surgical patients. Journal of Post Anesthesia Nursing 8:322-326, 1993
Kelly JU, Kelly TJ: Insulin-dependent diabetes. Its effect on the surgical patient. Association of Operating Room Nurses Journal
54:61-68, 1991
Endocrinology and Diabetes. In The Children's Hospital at Westmead handbook: clinical practice guidelines in paediatrics. 4th ed.
Henry Kilham, David Isaacs, Eds. Sydney, McGraw-Hill Australia Pty Ltd, 186-216, 2004
122
Sick day management is the term used to describe the management of a child or adolescent
with diabetes who develops an intercurrent illness.
Diabetes and Infectious Illnesses
Children and adolescents with well-controlled diabetes have no greater risk of acquiring
infections than the general population, but having diabetes does introduce the need for extra
caution in the management of sick days.
While there are no epidemiological studies in children looking at independent risk factors
for infection in diabetes, many in vitro models have suggested altered immunity affecting
neutrophil function,1-3 although the exact relationship with glycaemic control remains
unclear. An association with glycaemic control is suggested by studies in diabetic adults
showing that more aggressive insulin therapy and blood glucose control post operatively can
improve neutrophil function in vitro,4 and decrease the incidence of wound infection post
operatively.5 Another study in critically ill adults (non diabetic) showed that intensive insulin
therapy to maintain blood glucose (BG) between 4.4 and 6.1 mmol/L compared with
conventional therapy (BG 10 – 11 mmol/L) reduced the mortality due to multi-organ failure
with a proven septic focus.6 The incidence of bacteraemia was decreased by 46% in the
intensive insulin therapy group.
Those with poorly controlled diabetes may have decreased immune defences against
infections resulting in:
• Increased risk of acquiring infections.
• Increased chance of infections spreading quickly.
• Increased risk of unusual infections (eg tuberculosis).
• Increased risk of infections from organisms that are not normally pathogenic.
• Poor response to antibiotics.
Diabetes may influence responses to the treatment of coexisting illnesses.
Impact of Illnesses on Diabetes
In general, children and adolescents with well-controlled diabetes cope with illnesses very
well.
Illnesses vary in their impact on the diabetes. Illnesses may cause:
• Little effect on blood glucose levels.
• Low blood glucose levels.
• High blood glucose levels.
Infections Causing Little Effect on Blood Glucose Levels
The key feature of these infections seems to be the lack of systemic upset and they often
cause no significant alteration in the metabolic status, eg intercurrent infections such as upper
respiratory tract infections, mild infectious mononucleosis or rubella. The transient fever
associated with immunisations is usually not associated with any problems with the diabetes.
123
Infections Causing Low Blood Glucose levels
Such illnesses are usually marked by nausea, vomiting and diarrhoea, but are not
accompanied by a fever or systemic features, and there is no increase in insulin resistance or
requirement. The problem seems to be mainly the inability to absorb or retain food. Common
causes are viral illnesses associated with mild gastritis (nausea and vomiting only) or a mild
gastroenteritis (vomiting and diarrhoea). Food poisoning may lead to a similar picture and
often the child may complain of abdominal discomfort or pain.
Infections Causing High Blood Glucose Levels
More commonly illnesses in childhood and adolescence raise blood glucose levels. Illnesses
associated with fever tend to raise blood glucose because of higher levels of stress hormones
and cytokines increasing gluconeogenesis and insulin resistance. In addition, ketones may
appear in the urine. Many of these infections have a silent prodromal phase which may cause
unexplained high glucose levels for several days before the illness declares itself.
Illnesses that cause raised blood glucose levels are usually those associated with general
malaise (lethargy, weakness, irritability, muscle aches, headache), fever and obvious signs of
an infection. The child or adolescent may feel nauseous, not feel like eating or drinking, and
may vomit.
Typical infections likely to be associated with increased insulin resistance:
• Viral illnesses associated with fever and systemic features, especially if associated with
vomiting. Common causes are viral pharyngitis, influenza, and the childhood illnesses
such as measles and varicella.
• Bacterial infections, especially if associated with fever. Common causes are tonsillitis,
ear infections, lower respiratory tract infections and urinary tract infections associated
with fever.
It is important for the child or adolescent to be seen by his/her doctor as bacterial illnesses
require antibiotic therapy or other specific therapy and the sooner these are started the better.
The combination of a high blood glucose level and ketones in the urine during illness is a
warning sign of a serious lack of insulin action in the body and is due to development of
insulin resistance. Treatment is urgent as without extra insulin this state may progress to
ketoacidosis.
General Principles of Sick Day Management
No studies were identified addressing insulin adjustment and sick day management in
children and adolescents with type 1 diabetes. However, current insulin regimens for sick day
management have stood the test of time.
The essential principles in sick day management are:
• Treat the underlying illness
The treatment of the underlying illness is no different in the child or adolescent with
diabetes, the only proviso being that medical assessment should be sought earlier in
case antibiotic or other therapies are required.
• Symptomatic relief
If a fever, headache or aches and pains are present, give regular paracetamol or
ibuprofen in recommended doses and make the child or adolescent comfortable.
124
•
Rest
Encourage bedrest and keep the child or adolescent at home if unwell.
• Sugar-free medications
It is important for the child or adolescent to take the medications as prescribed. For
young children, many syrups are available in sugar-free forms (antibiotics, paracetamol,
ibuprofen) and those not sugar-free are usually satisfactory as the amount of sugar
present in each dose is not large enough to cause a problem. For older children and
adolescents, most medications are available in tablet or capsule form and these are
sugar-free.
• Hydration
Encourage plenty of fluids. A child or adolescent with a fever loses more fluid due to
the increased body temperature. There may be continuing losses of quite large volumes
of fluid because of glycosuria causing an osmotic diuresis. It is important to remember
that because of the osmotic diuresis even markedly dehydrated children or adolescents
with diabetes can progress to more severe dehydration if the blood glucose remains
high. If the blood glucose is >15 mmol/L water or low joule drinks should be offered so
as not to raise the blood glucose further.
• Preparation for sick days
Each family should have a sick day kit prepared and ready to use (see Table 11.1).
Table 11.1: Emergency Kit for Sick Day Management at Home
• Rapid-acting insulin or short-acting insulin.
• Glucose test strips, meters and lancets/finger pricking devices.
• Urine test strips for glucose and ketone estimation or blood ketone meter and strips.
• Doctor’s/hospital’s phone number.
• Sweet cordial/fruit juice/lemonade or other soft drinks (caffeine is not recommended).
• Low joule (diet drinks) or water.
• Glucagon.
• Diabetes manual or emergency guidelines, including sick day foods.
• Thermometer.
• Diary.
• Paracetamol or ibuprofen - sugar-free syrup or tablets.
•
Education on sick day management
There are several key concepts that must be taught to all families:
Insulin must never be omitted.
Glucose levels during illness may rise, even in the absence of any ingested food due
to gluconeogenesis.
Vomiting is a serious sign.
The presence of ketones in the urine or blood with high blood glucose is a serious
sign.
Families must be aware of the signs that indicate the condition is too serious to treat at home
(see Table 11.2).
• General nutrition
If the child or adolescent is anorexic, encourage oral intake by tempting with fluids and
foods that may appeal (see Table 11.3).
125
Table 11.2: Indicators for Patient to be Transferred to Hospital
Sick day management at home should be abandoned and transfer to hospital arranged if:
• Vomiting persists, especially if it is frequent or becomes bile-stained.
• Hyperventilation occurs suggestive of Kussmaul respiration.
• Ketones are present and are increasing.
• Blood glucose continues to rise despite treatment.
• The child or adolescent becomes more unwell, drowsy, disoriented or confused.
• The nature of the illness is not understood.
• Abdominal pain is severe or localised.
• The caregivers are uncertain about how to handle the situation.
• The caregivers become exhausted.
• Other diseases coexist (e.g. cystic fibrosis).
• The patient is very young (e.g. under 2 years).
Table 11.3: Sick Day Foods and Fluids
The following quantities are approximately 1 exchange (15 gm of carbohydrate)
Fluids:
• _-_ cup orange, apple or pineapple juice.
• tea/water with 1 tablespoon of sugar or 1_ tablespoons of honey.
• _ cup of milk (170 ml) with 1 tablespoon of sweet drinking powder.
• _ cup of sweet soft drink.
Foods:
• Slice of bread or toast.
• _ cup potato or 1 medium size potato.
• _ cup boiled rice.
• _ English muffin.
• 2-3 plain dry biscuits.
• 2 scoops of ice-cream.
• 200 gm unsweetened yoghurt or _ carton (100 gm) sweetened yoghurt.
• _-_ cup unsweetened tinned fruit.
• _ cup sweet jelly.
• 1 small banana.
• 1 medium orange.
• 7 small jelly beans.
Insulin Regimens in Infections associated with Hyperglycaemia and Ketosis
Management at home
Additional insulin given at home can frequently avert hospitalisation in illnesses associated
with hyperglycaemia and ketosis.
The additional insulin used is short-acting or rapid-acting insulin given every 2-4 hours as
additional injections equal to 10-20 percent of the total insulin daily dosage.
The dosage, the frequency and the route of injection will vary according to the particular
circumstances for the particular patient.
The factors that have to be taken into account are:
• The degree of elevation of the blood glucose level.
• The length of time the blood glucose levels have been elevated.
• The patient’s age (extra caution in the very young).
• The total insulin dosage during a normal day.
126
•
•
Presence or absence of urinary ketones.
The response to the previous dose of insulin.
In general, 20 percent of total daily dosage is used for the additional injections if the patient is
very sick, has blood glucose in excess of 15 mmol/L and has moderate or larger amounts of
ketones in the urine. An acceptable regimen is shown below in Table 11.4.
Table 11.4: How to Calculate the Amount of Extra Insulin on Sick Days7;8
Blood
Urine
Blood
glucose
ketones
ketones
Management
(mmol/L)
(mmol/L)*
15
Negative
<1*
Do not give extra insulin.
Check blood glucose and ketones again in two hours.
>15
Negative
<1*
Re-check blood glucose in two hours.
Blood glucose may fall without extra insulin.
If persistently elevated consider an extra 5% of TDD
(total daily dose) of insulin.
>15
Trace
1.0-1.4* Give an extra 5 to 10% of TDD every 2-4 hours.
or small
Check blood glucose and ketones again in two hours.
>15
Moderate or
1.5*
Give an extra 10 to 20% of TDD every 2-4 hours.
large
Check blood glucose and ketones every hour.
Note: Extra insulin may be given as rapid-acting insulin or short-acting insulin analogues. To calculate the
Total Daily Dose (TDD) add up all the insulin given on a usual day (ie. Rapid-acting + intermediate/longacting). Do not include additional boluses given for unexpected hyperglycaemia.
*
Adapted from sample algorithm 8, no data available from clinical trials.
If a rapid response is required, the short-acting insulin can be given intramuscularly every 2
hours (Note: syringes with 8mm needles may not reach the muscle compartment). This
should be only under the direction of an endocrinologist and is outside the usual protocols
supervised by diabetes educators. Normally the condition is less urgent and the injections are
given subcutaneously at 4-hourly intervals until there is improvement.
Once the blood glucose is less than 15 mmol/L but above 12 mmol/L, repeated doses are
usually 10 percent of the total daily dose given every 4 hours (in addition to the usual
insulin).
Management in hospital
If the patient requires transfer to hospital for any reason (see Table 11.2) the management
should include the following:9
• If blood glucose level is >15 mmol/L and there are moderate or large ketones, but with
no or only mild ketoacidosis (venous pH >7.20).
IV fluids should be commenced (0.9% Saline initially at maintenance plus
replacement of estimated deficits over 24-48 hours.
Extra doses of short/rapid-acting sub-cutaneous insulin (10-20% of the total daily
dose given as short/rapid acting) are given every 2-4 hours until BG level <15
mmol/L and ketones have cleared.
• Once BG level falls below 15 mmol/L, dextrose should be added to the IV fluids. The
recommended dextrose containing fluid is N/2 Saline + 5% dextrose. This can be made
by adding 25 ml of 50% dextrose to 500 ml of N/2 Saline + 2.5% dextrose.
• Grade to oral intake when possible.
127
Insulin Regimens in Infections Associated with Persistent Hypoglycaemia
Management at home
These illnesses are marked by semi-starvation due to extreme anorexia, often associated with
vomiting and diarrhoea. The need is for frequent blood glucose testing, frequent sips of
sugar- or glucose-containing drinks or small portions of easily absorbed carbohydrate foods.
Insulin doses should be reduced but must not be suspended. In twice-daily insulin regimens
the short/rapid-acting insulin can be greatly reduced or possibly even omitted. The
intermediate insulin dosage may need reductions of 20-50 percent.
In basal-bolus regimens the short/rapid-acting doses may need to be reduced by 20-50
percent and the intermediate insulin by 20-50 percent.
Management in hospital
If the blood glucose level cannot be maintained by oral intake:
• IV fluids should be commenced with N/2 Saline + 5% dextrose.
• The BG level should be checked every 1-2 hours.
• Insulin doses should be reduced as described above.
Glucagon
For severe hypoglycaemia, in the hospital setting, the preferred treatment is intravenous
glucose (bolus dose 2-5 ml/kg of 10% dextrose over a few minutes) followed by dextrosecontaining maintenance fluids (see also severe hypoglycaemia). Intravenous dextrose raises
the blood glucose level faster than intramuscular glucagon.10;11 When intravenous access is
difficult or outside the hospital setting, severe hypoglycaemia should be treated with
intramuscular glucagon injection. The recommended dose is 0.5 units (or mg) for children
<25kg or <8 years old and 1.0 units (mg) for older children or those weighing >25kg).12
Remember that glucagon may make the child or adolescent vomit.
Minidose Glucagon
Under the supervision of a doctor or diabetes educator it is possible to prevent or treat ongoing mild hypoglycaemia in a child unwilling to eat or drink in an ambulatory setting with
small doses of subcutaneous glucagon.13 If hypoglycaemia is mild, ongoing or is impending
(ie blood glucose <4.4 mmol/L associated with gastroenteritis or food refusal),13 an injection
of a small dose of glucagon may reverse the hypoglycaemia without causing nausea and
vomiting and enable oral fluids to be re-established. This may prevent hospitalisation in some
cases. The recommended dose regimen is detailed below. Following the use of mini-dose
glucagon continued monitoring is imperative.
Table 11.5: Recommended Dose for Mini-dose Glucagon13
Quantity
Age
(yrs)
mcg (µg)
mg
ml
2
2 – 15
>15
20
10 per year of age
150
0.02
0.01 per year of age
0.15
0.02
0.01 per year of age
0.15
Units on insulin
syringe
2
1 per year of age
15
128
Insulin Pump Sick Day Management
The key points in the management of sick days are the same for insulin pump users as for
those on insulin injections. As people on pumps use only rapid-acting insulin and do not have
any injected depot of long-acting insulin, diabetic ketoacidosis can develop rapidly and
therefore hyperglycaemia must be taken very seriously.
If the blood glucose level is 15 mmol/L or above, the following steps should be taken:
• Immediately check for problems with the pump or delivery system.
• Check for ketones in the blood or urine.
• Proceed as directed in Table 11.6 depending on ketone result.
• To overcome insulin resistance, the basal rate and/or correction boluses may need to be
increased during the period of illness.
Table 11.6: Management of Sick Days with Insulin Pump14
If urine ketones are negative or small or
If urine ketones are moderate or high or
blood ketones less than 0.6 mmol/L.
blood ketones more than 0.6 mmol/L, or you
don’t think the pump is working.
• Give a correction bolus with the pump
• There may be a pump delivery problem or a
(see Insulin pump adjustments – Chapter
significant illness developing.
5).
• Liaise with diabetes pump team.
• Test the BG hourly.
• Use injected insulin given with a syringe or
• Drink extra low joule fluids.
pen to deliver the correction bolus dose (see
• If BG is lower after 1 hour, recheck again
Insulin pump adjustments - Chapter 5).
in 1 to 2 hours and decide if another
• Drink extra unsweetened (low joule) ‘diet’
correction bolus dose is needed (use the
fluids.
unused bolus rule, see Insulin pump
• Test the BG hourly.
adjustments - Chapter 5).
• Replace the insulin in the pump, and the
infusion set and cannula. Do not use the
• If the BG is not lower after the first bolus
pump again until the situation is under
proceed to give an injection with a syringe
control.
or pen (see column 2).
• If after 2 hours there is no improvement,
liaise with diabetes pump team.
• If after 2 hours the BG is improved, use the
unused bolus rule to decide if an additional
bolus is needed (see Insulin pump
adjustments - Chapter 5). Pump use can be
resumed.
• If BG remains high, ketones persist, or
nausea, vomiting or abdominal pain develop,
liaise with diabetes pump team or immediate
hospital assessment recommended.
Table adapted from Walsh and Roberts: Pumping insulin. Everything you need for success with an insulin
pump.15
When patients are eating less their meal boluses should be decreased; however as food
absorption may be poor during the illness, it may be necessary to decrease insulin boluses to
even less than the usual ratio. The basal insulin rate may also need to be decreased if the
blood glucose still tends to be low.
Hypoglycaemia should be treated in the usual way.
129
The Evidence
No studies were identified addressing insulin adjustment and sick day management in
The evidence for the management of severe hypoglycaemia (intravenous glucose versus
intramuscular or intravenous glucagon) is listed in Evidence Table 11.1.
• Intravenous dextrose raises the blood glucose level faster than intramuscular
glucagon.10;11(II)
The evidence for the management of mild or impending hypoglycaemia using minidose
glucagon is listed in Evidence Table 11.1.
• In a small case series, 28/33 children with type 1 diabetes who had gastroenteritis with
impending hypoglycaemia, were effectively managed at home with small doses of
intramuscular glucagon.13(IV)
• Families should be informed that intercurrent illnesses can cause high or low blood
glucose levels.7;16;17(C)
• All families should receive education about the management of sick days and have a sick
day kit at home containing rapid-acting or short-acting insulin, glucose test strips, meters,
lancets/finger pricking devices, urine test strips for glucose and ketone estimation or blood
ketone meter and strips, doctor’s/hospital’s phone number, sweet cordial/fruit
juice/lemonade or other soft drinks, low joule (diet drinks) or water, glucagon, diabetes
manual or emergency guidelines, sick day foods, thermometer, paracetamol or ibuprofen
(sugar-free syrup or tablets).7;16;17(C)
7;16;17
• Insulin should never be omitted even if unable to eat.
(C)
7;16;17
• Blood glucose and ketones should be monitored frequently.
(C)
7;16;17
• Any underlying illness should be treated promptly.
(C)
• Extra oral fluids should be encouraged especially if the blood glucose is high or ketones
are present.7;16;17(C)
• Additional boluses of short/rapid-acting insulin equal to 10-20 percent of the total insulin
daily dosage should be given every 2-4 hours if the blood glucose is high and ketones are
present.7;16;17(C)
• Patients/carers should seek assistance immediately if, after extra insulin boluses, the blood
glucose remains high, ketones persist, or nausea, vomiting or abdominal pain develop.
7;16;17
(C)
•
Severe hypoglycaemia should be treated with intravenous dextrose (in the hospital
setting).10;11(II)
• If venous access is difficult or outside the hospital setting, intramuscular glucagon should
be used to treat severe hypoglycaemia.7;16;17(C)
• Under the supervision of a doctor or diabetes educator, small doses of subcutaneous
glucagon may be used to prevent or treat mild hypoglycaemia in an ambulatory setting.
13
(IV)
130
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Mowat A, Baum J: Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. New England Journal of
Medicine 284:621-627, 1971
Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B: Impaired leucocyte functions in diabetic patients.
Diabetic Medicine 14:29-34, 1997
Gallacher SJ, Thomson G, Fraser WD, Fisher BM, Gemmell CG, MacCuish AC: Neutrophil bactericidal function in diabetes
mellitus: evidence for association with blood glucose control. Diabetic Medicine 12:916-920, 1995
Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP: Insulin infusion improves neutrophil function in diabetic
cardiac surgery patients. Anesthesia & Analgesia. 88:1011-1016, 1999
Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A: Glucose control lowers the risk of wound infection in
diabetics after open heart operations. Annals of Thoracic Surgery 63:356-361, 1997
van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon
R: Intensive insulin therapy in the critically ill patients. New England Journal of Medicine 345:1359-1367, 2001
Ambler G, Barron V, May C, Ambler E, Cameron F: Caring for Diabetes in Children and Adolescents. A parents manual. Sydney,
Laffel L: Sick-day management in type 1 diabetes. Endocrinology & Metabolism Clinics of North America 29:707-723, 2000
Royal Alexandra Hospital for Children: Endocrinology and Diabetes. In The New Children's Hospital Handbook. Kilham H, Isaacs
D, Eds. Sydney, 1999, p. 170-193
Medicine 7:73-77, 1990
Collier A, Steedman DJ, Patrick AW, Nimmo GR, Matthews DM, MacintyreCCA: Comparison of intravenous glucagon and
MediMedia Australia Pty Limited: MIMS Australia. 2003
Haymond MW, Schreiner B: Mini-Dose Glucagon Rescue for Hypoglycaemia in Children With Type 1 Diabetes. Diabetes Care
24:643-645, 2001
Ambler G, Groves G: Guide to Insulin Pump Therapy. The Children's Hospital at Westmead. 2003
Walsh J and Roberts R: Pumping insulin. Everything you need for success with an insulin pump. Torrey Pines, 2000
131
Hypoglycaemia is the most frequent acute complication of type 1 diabetes.1
It is the major factor limiting intensified regimens aiming for near-normoglycaemia.1;2
Severe hypoglycaemia is rated as the most anxiety-promoting feature of diabetes by both
children and parents and may lead to loss of self-esteem and social isolation.
Hypoglycaemia does not appear to cause permanent neuro-psychological impairment in
adults3-5 but may do so in younger children.6-10 Hypoglycaemia should be avoided in
children, especially in those under 5 years of age.11
Definition
There is no agreed definition of hypoglycaemia. The blood glucose level at which
hypoglycaemic clinical features occur varies considerably between individuals and even
within the same individual.12;13
Hypoglycaemia may be symptomatic or asymptomatic (hypo unawareness). The level at
which hypoglycaemia is recognised by the individual is influenced by preceding
hypoglycaemic episodes and also by preceding hyperglycaemia.14;15 The individual’s
recognition of hypoglycaemia is predominantly due to the autonomic features (see below).
Recognition of neuroglycopenic features varies considerably but may be improved in adults
by specific blood glucose awareness training programmes.14;16-21
Young children may not be able to recognise the clinical features of hypoglycaemia.
Counter-regulatory hormone and symptom responses to falling glucose levels develop at
higher levels in children than adults and may be detected at plasma glucose values between
3.5 and 4.0 mmol/L. Children and adolescents with poor glycaemic control may experience
symptoms and hormonal responses at even higher, sometimes normal, glycaemic levels.12
Whilst the precise definition of what constitutes hypoglycaemia remains controversial
parents and children need to know what levels of glucose to respond to. The brain needs a
constant supply of glucose, and cognitive defects in children and adolescents with diabetes
have been found at glucose values between 3.3 and 3.6 mmol/L.13 As a result, it is advisable
to maintain blood glucose values above 4.0 mmol/L in children with diabetes.
Symptoms and Signs
As in adults, symptom responses to hypoglycaemia in children or adolescents may be divided
into those described as autonomic or neuroglycopenic.
The autonomic symptoms and signs may be:
• Cholinergic (sweating, hunger, tingling around the mouth).
• Adrenergic (tremor, tachycardia, pallor, palpitations and anxiety).
Neuroglycopenic symptoms and signs include:
• Weakness.
• Headache.
• Visual disturbance.
• Slurred speech.
• Vertigo and dizziness.
• Difficulty in thinking.
• Tiredness.
• Drowsiness.
132
•
•
•
•
Change in affect (eg depressed, angry, argumentative).
Mental confusion.
Coma.
Convulsions.
Usually autonomic responses occur before neuroglycopenic features however in
hypoglycaemia unawareness, neuroglycopenic features occur before autonomic features
(which may be absent).
Parents and caregivers usually recognise symptoms of hypoglycaemia in younger children
who show behavioural changes such as irritability or show changes in appearance such as
pallor and sweatiness.
The symptoms of hypoglycaemia may not always be the same for a given blood glucose
level and parents and caregivers need to be aware of the protean nature of the clinical features
possible during hypoglycaemia.
Table 12.1: Symptoms of Hypoglycaemia in Diabetic Children and Recommendations
for its Treatment
Severity
Clinical Features
Treatment
Mild
Mild autonomic features (adrenergic Juice, sweet lemonade, cordial,
and cholinergic) - hunger, shakiness, snack. If the hypoglycaemia is
tremor, nervousness, anxiety,
very mild it may be possible to
sweatiness, pallor, palpitations and
bring forward the scheduled
tachycardia. Mild neuroglycopenia – meal if episode occurs within
decreased attention and cognitive
15-30 minutes of a planned
performance.
meal.
Moderate
Moderate neuroglycopenic and
10-20 gm of easily absorbed
autonomic features - headache,
carbohydrate followed by a
abdominal pain, behaviour changes,
snack with carbohydrate foods.
aggressiveness, impaired or double
vision, confusion, drowsiness,
weakness, difficulty in talking,
tachycardia, dilated pupils, pallor,
sweatiness.
Severe
Severe neuroglycopenic features Outside hospital: Glucagon by
extreme disorientation, loss of
injection (s.c., i.m. or i.v.) 0.5
consciousness, focal or generalised
mg <8 years of age or <25kg,
seizures.
1.0 mg >8 years of age or
>25kg. If no response in 10
minutes, check blood glucose.
If still low repeat once. Followup with carbohydrate foods and
frequent monitoring.
In hospital: intravenous
dextrose (2-5 ml/kg body
weight of 10% dextrose)
followed by 5-10% dextrose
infusion to maintain blood
glucose level between 5-10
mmol/L.
133
Grading
Hypoglycaemia may be symptomatic or asymptomatic.22
Symptomatic hypoglycaemia can usefully be divided into three grades on the following
clinical criteria:
• Grade 1 or mild when the child or adolescent with diabetes is able to detect and treat
the hypoglycaemia himself/herself. Hypoglycaemia occurring in children under the age
of 5 years can not be classified as grade 1 or mild because young children are not able
to treat themselves.
• Grade 2 or moderate hypoglycaemia occurs when someone else has to go to the aid of
the child or adolescent with diabetes, but treatment is possible orally.
• Grade 3 or severe hypoglycaemia occurs when the child or adolescent is unconscious,
convulsion or unable to take oral glucose because of extreme disorientation and the
only therapy is either glucagon by injection or intravenous glucose.
Frequency
In the Diabetes Control and Complications Trial, adolescents receiving intensive therapy had
86 episodes of hypoglycaemia per 100 patient-years requiring assistance and 27 episodes of
hypoglycaemic coma or seizures per 100 patient-years. Adolescents on conventional therapy
had 28 and 10 episodes per 100 patient-years respectively.23
In the UK, a national audit of children aged less than 17 years with type 1 diabetes
reported that 4% experienced one or more episodes of severe hypoglycaemia per year.24
In a recent audit of glycaemic control in NSW and ACT, the prevalence of severe
hypoglycaemia (coma or convulsion) was 36 episodes per 100 patient-years.25;26 In Western
Australia (in 1995), the incidence of severe hypoglycaemia (coma or convulsion) was 15.6
per 100 patient-years.27
Adolescents have a higher incidence of moderate and severe hypoglycaemia despite
having higher HbA1c levels than adults.23;28;29 The increased risk of hypoglycaemia in
adolescence may be related to:
• The need for larger insulin doses during the phase of rapid growth.
• Irregular diet.
• Irregular activity levels.
Nocturnal Hypoglycaemia
Nocturnal hypoglycaemia is frequent, often prolonged and may be asymptomatic.30 Nocturnal
hypoglycaemia does not necessarily disturb sleep patterns. It may be suspected if prebreakfast blood glucose is low, confusional states, nightmares or seizures occur during the
night or impaired thinking, lethargy, altered mood31 or headaches are experienced on waking.
Counter-regulatory responses may be impaired during sleep.32;33
Nocturnal hypoglycaemia is not reliably predictable on the basis of a bedtime blood
glucose level;34 therefore, blood glucose monitoring with regular measurements after
midnight is essential to detect nocturnal hypoglycaemia.
Nocturnal hypoglycaemia may be reduced by careful attention to the dose and type of
insulin used. The 11pm blood glucose level does not accurately predict the 2am blood
glucose level.34 Periodic early morning blood glucose levels are recommended.
134
Consequences
The adverse consequences of hypoglycaemia include:
• Injury or accident during a hypoglycaemic episode. A recent international multicentre
survey of drivers with type 1 diabetes found that they are at increased risk for driving
mishaps than drivers who do not have type 1 diabetes.35
• Death.
Hypoglycaemia was implicated in 8% of diabetes related deaths in children
<20years old.36
• Fear of hypoglycaemia by the parents of a young child. This often interferes with any
attempts to improve control.37 Similarly, for an adolescent, an unexpected
hypoglycaemic episode is an embarrassment that he/she may seek to avoid, even at the
expense of hyperglycaemia and poorer control.
• Direct effects of hypoglycaemia on the brain.
Although no adverse neuropsychological effects have been demonstrated in adults
following severe hypoglycaemia,3;4;38 there are greater concerns about the
consequences of hypoglycaemia in young children because of the continued growth
and development of the brain. Cognitive deficits have been reported in children who
have developed diabetes before the age of five years, or if the child has had
hypoglycaemia induced seizures.6-9;39;40 Both inadequate glycaemic control and the
sensitivity of the young brain to hypoglycaemia may account for these findings. In
children who have developed diabetes after the age of 5 years, this difference has
not been found.
• In a recent cost-of-illness study hypoglycaemia was found to have significant
socioeconomic costs.41
Counter-Regulatory Responses to Hypoglycaemia and Hypoglycaemia Unawareness
In non-diabetic individuals, a number of responses are generated by insulin-induced
hypoglycaemia. Initially, endogenous insulin secretion is suppressed at an early stage.
Secondly, glucagon and adrenaline, the rapid-acting counter-regulatory hormones, are
promptly released.42 This results in glycogenolysis, but if hypoglycaemia is prolonged,
gluconeogenesis is also stimulated. Adrenaline has additional effects on peripheral glucose
utilisation and stimulates lipolysis. Finally, when hypoglycaemia is prolonged, growth
hormone and cortisol responses increase hepatic glucose production and suppress glucose use
in peripheral tissues.42
The integrity of glucose counter-regulation is disturbed by type 1 diabetes.12;43 In diabetic
subjects receiving insulin by injection, insulin levels cannot therefore be suppressed and in
addition glucagon responses to insulin-induced hypoglycaemia are characteristically lost.
Unfortunately adrenaline responses may also be disrupted.
The reduction in adrenaline responses may be:
• Permanent.
• Reversible and be the result of hypoglycaemia per se, ie. hypoglycaemia-associated
autonomic failure.
Hypoglycaemia-associated autonomic failure is often associated with loss of symptomatic
responses.14;16;21 It may be reversible by prevention of hypoglycaemia.
The development of hypoglycaemia unawareness in childhood should lead to suspicion of
previous episodes of undiagnosed hypoglycaemia (often nocturnal).44
135
Prevention
Hypoglycaemia in children is largely preventable. However there is a significant proportion
of severe hypoglycaemic episodes in which no obvious cause can be determined. The most
common causes of hypoglycaemia are:
• Inadequate or missed meals or snacks.
• Physical activity (unplanned or more prolonged than usual) without appropriate food
intake.
• Insulin administration errors (eg inadvertent reversal of morning and evening doses or
of the short/rapid- and intermediate-acting insulins).
• Alcohol ingestion (resulting in impaired hepatic gluconeogenesis).
• Idiopathic (no obvious cause discernible). It is likely that some of these are related to
variations in insulin absorption.
All children and adolescents with diabetes should carry glucose tablets or readily absorbed
carbohydrate foods (preferably in waterproof sealed wrap) on their person and have glucagon
available at home (and in boarding schools where there is a nurse on staff).
Children and adolescents with type 1 diabetes should be encouraged to wear a MedicAlert37;45 (or similar warning information), and people rendering first aid should be made
aware to look for such warning devices.
Adequate parental education and support should be available so that proper insulin and
dietary adjustments can be made to reduce the risk of hypoglycaemia. For example, parents
and children should be taught how to deal with unusual exercise and events such as school
camps.
Confirmation
Although it is useful to have the hypoglycaemia confirmed by a blood glucose measurement,
treatment is urgent and should not be withheld if undue delay is likely.
Treatment
Mild to moderate hypoglycaemia
Treatment involves immediate consumption of 10-20 gm of an easily absorbed form of
carbohydrate, followed by a snack of carbohydrate foods to maintain normoglycaemia until
the next meal or snack.45
Glucose cannot be absorbed from the oral cavity therefore massaging the outside of the
cheek against the gum is not effective.46
In adults, a RCT crossover study compared the rises in blood glucose levels after various
therapies for hypoglycaemia. After 10 gm oral glucose, peak BG level reached 5.4 ± 0.4
mmol/L, after 20 gm oral glucose peak BG level reached 6.8 ± 0.7 mmol/L and after 1 mg
glucagon peak BG level reached 11.8 ± 0.8 mmol/L.47
Lemonade and glucose tablets (which must be easily chewable) are examples of
appropriate foods for the treatment of mild to moderate hypoglycaemia.
If giving a drink to a hypoglycaemic child, it is useful to put the child’s hands around the
cup and to guide the cup to the mouth. This minimises the natural reaction of rejecting the
drink. Insulin and dietary adjustments should be made to prevent further hypoglycaemia
when appropriate.
136
Severe hypoglycaemia
For severe hypoglycaemia therapy is urgent. People who are either unconscious or fitting are
unable to swallow. Nothing should be given by mouth. The airway should be checked to
ensure that respiration is unhampered, the person should be placed on their side (resuscitation
position) to prevent aspiration of material into the lungs and emergency services (dial 000)
called.
Parents are taught to administer glucagon by injection according to the manufacturer’s
instructions. The recommended dose is 0.5 units (or mg) for children who are <25kg or <8
years old, and 1.0 units (mg) for older children or those weighing >25kg. All children and
adolescents with diabetes should have glucagon at home and their families shown (by ‘hands
on’ practice during diabetes education sessions) how to administer it in times of severe
hypoglycaemia. Following treatment with IM glucagon, further treatment with intravenous
dextrose by emergency services may occasionally be required if hypoglycaemia persists.
Glucagon is normally administered intramuscularly or subcutaneously but can also be
given intravenously in the hospital setting. Glucagon frequently causes nausea and
vomiting.48
Figure 12.1: Glucagon Kit for Treatment of Hypoglycaemia
Intravenous glucose (dextrose) is more rapid at reversing hypoglycaemia than IM49 or IV50
glucagon. However, intravenous glucose can only be administered by doctors or specially
trained health care professionals such a paramedics or intensive care ambulance officers. The
dose is 0.2-0.5 gm/kg body weight. This can be given as 2-5 ml/kg of 10 percent dextrose. If
25 percent dextrose is used, the dose is 1.0-1.5 ml per kg body weight, but care must be taken
not to exceed this because of the danger of causing severe hyperglycaemia rapidly. The
dextrose should be given slowly over a few minutes. Care should be taken to avoid
extravasation because its hyperosmolality may cause local tissue irritation or necrosis. 50%
dextrose should not be used.
Intramuscular epinephrine (0.3 mg) has been shown to be less effective than IM glucagon
(1.0 mg) in raising the blood glucose at 15 minutes (2.6 ± 0.2 versus 0.5 ± 0.3 mmol/L).51
Other therapies which have been shown to have effect in adult studies include oral terbutaline
(5.0 mg), subcutaneous terbutaline (0.25 mg) and oral alanine (40 gm).47 Glucagon remains
the drug of choice if intravenous dextrose is not readily available.
Follow-Up of Treatment of Hypoglycaemia
The initial treatment for hypoglycaemia may need to be repeated if follow-up blood glucose
testing indicates a recurrence or continuation of the hypoglycaemia.
137
Many children vomit persistently after severe hypoglycaemia, especially after glucagon.
After the emergency treatment of the hypoglycaemia, it is necessary to ensure that the
hypoglycaemia does not recur and hence the following actions are needed:
• Frequent measurement of blood glucose levels.
• Ensuring that food is tolerated (either as frequent small amounts of sugary drinks or an
adequate amount of easily absorbed carbohydrate).
• Supervision by a relative or friend who should accompany the person home.
• Arranging an early appointment with the doctor for review of diabetes management.
• If food is not tolerated, then hospitalisation for a continuous infusion of 5-10 percent
dextrose and frequent monitoring is necessary.
Hypoglycaemia and Physical Activity
Hypoglycaemia may occur during, immediately after or many hours after physical activity.
Special attention should be given to children and adolescents performing intensive sports,
especially those involving endurance training, due to the association with delayed
hypoglycaemic reactions which may occur in the middle of the night or before breakfast the
next day. Advice should be sought from a dietitian for foods suitable for those undertaking
endurance sports.
Most sports days can be readily managed by increasing caloric intake during and after the
sport. A general recommendation is that an extra serve of easily absorbable carbohydrate be
taken for every half hour of sport. Requirements for extra carbohydrate with physical activity
are very individual.
Intensive sports need to have appropriate reductions made in dosages of the insulin acting
during and for the following 12-24 hours after the physical activity.
Blood glucose levels need to be measured before, during and after intensive sport.
Experience and blood glucose monitoring help determine the most appropriate strategies.
All children and adolescents participating in sport should have access to help in case of
hypoglycaemia. Participating in physical activity in isolation should be discouraged. Those
involved in strenuous and potentially dangerous sports should have a ‘buddy’ able to offer
assistance.
If weight gain is an issue, decreasing insulin before exercise lessens the need for extra
food.
Somogyi Phenomenon
The concept of hypoglycaemia causing rebound hyperglycaemia was generally referred to as
the Somogyi phenomenon or effect.52 Fasting hyperglycaemia was thought to be due to a
counter-regulatory overshoot of the blood glucose following unrecognised nocturnal
hypoglycaemia.52;53 Whilst the Somogyi phenomenon has been shown to exist, the dawn
phenomenon and the waning of insulin levels are more likely causes of prebreakfast
hyperglycaemia.53-55
Hypoglycaemia in School
Teachers and carers at schools should be informed as to the symptoms of hypoglycaemia and
appropriate treatment. They should also have access to advice when necessary.
It may be useful for a member of the diabetes team to visit the school and provide this
education to the teacher.
138
Children should not be restricted in activities at school but extra carbohydrate should be
given prior to sports or physical education activities. Easily absorbed carbohydrate should be
available at school.
Foods for Management of Hypoglycaemia
Examples of the foods suitable for the management of hypoglycaemia are indicated below.
Easily absorbed carbohydrate should be followed within 15-20 minutes by a choice of
carbohydrate foods to maintain blood glucose levels.
Easily absorbed carbohydrate to begin with:
• 125-200 ml ordinary soft drink or diluted cordial.
• 4 large jelly beans, 7 small jelly beans.
• 2-3 teaspoons of sugar.
• Glucose tablets (10-20 gm).
Carbohydrate foods to follow up with (equivalent to 15 gm carbohydrate or 1 exchange):
• 1 slice of bread.
• 1 banana or apple.
• 200 gm unsweetened yoghurt or 100 gm sweetened yoghurt.
• 1 glass of milk (300 ml).
The Evidence
The evidence for the effect of intensive diabetes management on the incidence of
hypoglycaemia in type 1 diabetes is listed in Evidence Table 12.1.
• In the Diabetes Control and Complications Trial, adolescents receiving intensive therapy
had 86 episodes of hypoglycaemia per 100 patient-years requiring assistance and 27
episodes of hypoglycaemic coma or seizures per 100 patient-years. Adolescents on
conventional therapy had 28 and 10 episodes per 100 patient-years respectively.23(II)
• In NSW and ACT, the prevalence of severe hypoglycaemia (coma or convulsion) was 36
episodes per 100 patient years.25;26(IV)
• A prospective study in Western Australia found that the incidence of severe
hypoglycaemia (coma or convulsion) increased from 4.8 to 15.6 per 100 patient-years in
parallel with a decrease in HbA1c from 10.2% in 1992 to 8.8% in 1995. This increase was
particularly marked in younger children (<6 years) in whom severe hypoglycaemia
increased from 14.9 to 42.1 episodes/100 patient-years.27(IV)
• Adolescents have a higher incidence of moderate and severe hypoglycaemia than adults
despite having higher HbA1c levels than adults.23;29(II)
The evidence for the management of severe hypoglycaemia (intravenous glucose versus
intramuscular or intravenous glucagon) is listed in Evidence Table 12.2.
• RCT’s have found that intravenous glucose (dextrose) is more rapid at reversing
hypoglycaemia than IM49 or IV50 glucagon.(II)
The evidence for the effects of hypoglycaemia on cognitive function in children and
adolescents with type 1 diabetes is listed in Evidence Table 12.3.
• Hypoglycaemia has been associated with neurocognitive dysfunction in children
especially if there is a history of hypoglycaemic seizures or if the child had early onset of
diabetes.6-10;39;40(II, III, IV)
139
The Consensus Statements used to formulate the recommendations and principles of clinical
practice are listed in Evidence Table 12.4.
23;25;26;27;29
• Hypoglycaemia is the most frequent acute complication of type 1 diabetes.
(II)
• Hypoglycaemia is the major factor limiting intensified regimens aiming for nearnormoglycaemia.23;25;26;27;29(II)
• Severe hypoglycaemia should be avoided in children, especially in those less than 5 yrs
old.6-10;39;40(II, III, IV)
• Blood glucose values should be maintained above 4.0 mmol/L in children and adolescents
with diabetes.37;56;57(C)
• Children and adolescents with diabetes should wear some form of identification or
warning of their diabetes.37;56;57(C)
• All children and adolescents with diabetes should carry glucose tablets or readily absorbed
carbohydrate (preferably in waterproof sealed wrap) on their person and have glucagon
available at home (and in boarding schools where there is a nurse on staff).37;56;57(C)
• Hypoglycaemia in children is largely preventable; however there is a significant
proportion of severe hypoglycaemic episodes in which no obvious cause can be
determined.56;57(C)
• School teachers and carers at schools should be informed of the symptoms and appropriate
treatment of hypoglycaemia and should have access to advice when necessary.37;56;57(C)
• In the hospital setting severe hypoglycaemia should be treated with intravenous dextrose
as this is the most rapid way of treating severe hypoglycaemia.49;50(II)
• The recommended dose of intravenous dextrose is 2-5ml/kg of 10% dextrose. 50%
dextrose should not be used because of dangers of tissue necrosis associated with
extravasation.(C)
• Intramuscular or subcutaneous glucagon is an effective way of treating severe
hypoglycaemia in a home-care setting or if intravenous dextrose is not possible.49;50(II)
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Reichard P, Pihl M: Mortality and treatment side-effects during long-term intensified conventional insulin treatment in the
Stockholm Diabetes Intervention Study. Diabetes 43:313-317, 1994
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Diabetes Control and Complications Trial. Annals of Internal Medicine 124:379-388, 1996
Austin EJ, Deary IJ: Effects of repeated hypoglycemia on cognitive function: a psychometrically validated reanalysis of the
Diabetes Control and Complications Trial data. Diabetes Care 22:1273-1277, 1999
study. Journal of Pediatrics 134:503-506, 1999
Hershey T, Bhargava N, Sadler M, White NH, Craft S: Conventional versus intensive diabetes therapy in children with type 1
diabetes: effects on memory and motor speed. Diabetes Care 22:1318-1324, 1999
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Jones TW, Boulware SD, Kraemer DT, Caprio S, Sherwin RS, Tamborlane WV: Independent effects of youth and poor diabetes
control on responses to hypoglycemia in children. Diabetes 40:358-363, 1991
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GB: Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness
and counterregulation. Diabetes 46:1172-1181, 1997
Jones TW, Borg WP, Borg MA, Boulware SD, McCarthy G, Silver D, Tamborlane WV, Sherwin RS: Resistance to
Neuroglycopenia: An Adaptative Response during Intensive Insulin Treatment of Diabetes. Journal of Clinical Endocrinology &
Metabolism 82:1713-1718, 1997
Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Di Vincenzo A, Modarelli F, Ciofetta M, Lepore M, Annibale B, Torlone E:
Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia,
following institution of rational, intensive insulin therapy in IDDM.[erratum appears in Diabetologia 1995 Feb;38(2):254].
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Cox DJ, Gonder-Frederick L, Polonsky W, Schlundt D, Kovatchev B, Clarke W: Blood glucose awareness training (BGAT-2):
long-term benefits. Diabetes Care 24:637-642, 2001
Kinsley BT, Weinger K, Bajaj M, Levy CJ, Simonson DC, Quigley M, Cox DJ, Jacobson AM: Blood glucose awareness training
and epinephrine responses to hypoglycemia during intensive treatment in type 1 diabetes. Diabetes Care 22:1022-1028, 1999
Cox D, Gonder-Frederick L, Polonsky W, Schlundt D, Julian D, Clarke W: A multicenter evaluation of blood glucose awareness
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Cox DJ, Gonder-Frederick L, Julian DM, Clarke W: Long-term follow-up evaluation of blood glucose awareness training. Diabetes
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Fanelli CG, Epifano L, Rambotti AM, Pampanelli S, Di Vincenzo A, Modarelli F, Lepore M, Annibale B, Ciofetta M, Bottini P:
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Davis EA, Keating B, Byrne GC, Russell M, Jones TW: Impact of improved glycaemic control on rates of hypoglycaemia in insulin
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Responses to Hypoglycemia during Sleep. New England Journal of Medicine 338:1657, 1998
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142
Impact on Child
Type 1 diabetes in childhood imposes a number of psychological stresses on both the child
and the family. Fluctuations in blood glucose levels may contribute directly to alterations in
behaviour and mood, with increased restlessness and irritability and reduced capacity to
concentrate.
A social worker and a clinical psychologist should be part of the multidisciplinary team
involved in the management of children and adolescents with diabetes.1
Psychological morbidity is increased in children with diabetes2;3 as it is in children with
other chronic illnesses.4
Initial adjustment to diabetes is characterised by sadness, anxiety, withdrawal, depression,
and dependency.5-7 Such difficulties often resolve within the first year, but poor adaptation in
this initial phase has been found to place children at risk for later emotional difficulties.8
Diabetes treatment routines may:9;10
• Impose a lack of spontaneity in lifestyles.
• Engender passivity and inappropriate dependence upon adults for decision-making and
self-care.
• Foster feelings of rebellion in some young people.
• Engender a loss of confidence.
Treatment regimens may be difficult to accept and may lead to some children and adolescents
struggling with developmentally appropriate issues of independence and autonomy.
Adolescents develop an increasingly sophisticated understanding of the implications of
chronic illness for future wellbeing, life opportunities, and career choices. This may cause a
sense of being ‘damaged’ at a time when a strong sense of self and an unlimited future are of
key importance for psychological well being.
An Australian prospective study of neuropsychological and psychosocial functioning
followed 133 children from diagnosis of type 1 diabetes. At ten years 36 percent of an
adolescent subset met the criterion for one or more DSM-IV diagnoses,10 approximately
double the prevalence reported in a recent Australian community sample of similar-aged
peers.11
Impact on Family
The diagnosis of type 1 diabetes itself is experienced as a significant psychological crisis in
which the parents grieve the loss of the idealised child. Family adaptation to illness is not a
static process, but must change to take account of the child’s developing maturity and
capacity for self-management of their condition.
Frequently expressed parental feelings include:
• Anxiety over the ever-present possibility of hypoglycaemia.
• Frustration over failure to achieve perfect glycaemic control.
• Concern over long term complications.
• Guilt and responsibility for transmitting the genetic components of diabetes.
• Diminished enjoyment of the parental role as parents struggle to balance the
psychological needs of the child with the restrictions and treatment requirements
imposed by the illness.
143
•
•
Higher parenting stress levels.7
Feeling less cohesive and more rigidly organised than control families.7
Other family members are also affected by the presence of a child with diabetes:
• Siblings may resent the extra parental time directed to the child with diabetes.
• Siblings may resent that family activities are curtailed to take account of the demands
of the diabetes regimen.
• Siblings may be fearful that they have caused the illness in their sibling.
• Family members may fear that they may themselves develop diabetes.
• Grandparents may be fearful of their ability to look after their grandchild.
• Grandparent’s desire to compensate the child may undermine parental management,
especially in regard to issues around food.
Type 1 diabetes in children and adolescents is associated with higher rates of psychiatric
disorders including adjustment disorders, major depression, anxiety disorders9 and eating
disorders.12 Psychiatric disorders in childhood increase the risk of subsequent psychiatric
disorders in adolescence and adulthood.13
Serious problems with self management in childhood diabetes tend to arise about 3.5 years
after diagnosis or in early adolescence and are difficult to treat.14 The optimal time for
interventions to address later problems with compliance in early adolescence appears to be in
the initial period following diagnosis when compliance tends to be high.14
Mild cognitive deficits have been observed to occur more frequently in children with type
1 diabetes; especially in those children who were first diagnosed under two years of age.15
Such deficits are associated with learning difficulties which may require specialist
recommendations and remediation for academic problems.
Clinical psychology assessment and early intervention for psychological problems in
children with type 1 diabetes and their families are essential to maximise health outcomes
Psychosocial Factors and Metabolic Control
Relationships between psychological factors (child adjustment, parental mental health, family
functioning) and metabolic control are of great interest in type 1 diabetes. Psychological
distress in siblings and adult family members may impair their relationship with the child
with type 1 diabetes, reducing opportunities for effective family support.
A number of studies have found an association between psychological difficulties in the
child and chronic poor metabolic control.10;16-19 Causality is unproven but it is assumed that
troubled children are less likely to adhere to treatment regimens, leaving them at ‘double
jeopardy’ for adverse physical and mental health outcomes.
In contrast, associations between mood disorders and family conflict and very ‘tight’ or
good metabolic control have also been reported,20-22 raising the possibility that neurotic
symptoms may either contribute to, or result from, obsessive pre-occupation with the
demands of the diabetes regimen.
In the Australian longitudinal study, adolescents were divided into three groups on the
basis of their metabolic control history.10 Fifty percent of the mixed poor control group
(HbA1c >9.5% for more than one third the time since diagnosis) had a psychiatric diagnosis
compared with twenty five percent of the well controlled group (no hyper- or
hypoglycaemia), with the hypoglycaemia group (no severe hypoglycaemia) falling between
these two extremes.10
144
Relationships between parameters of family functioning and metabolic control in the child
have shown:
23;24
• Rigidly organised, inflexible families have been associated with both better
and
25
poorer metabolic control in the child.
• Strict parental supervision was associated with better health outcomes but greater
psychological dependency in the child.23
Metabolic control and psychological outcomes do not always coincide. Over-zealous
adherence with treatment regimens may have a psychological cost for some children.
Psychological dependency on parents exerting strict control may lead to failure of the child to
develop age appropriate competencies and self management strategies necessary for effective
metabolic control in adolescence and early adulthood.
Adherence to Therapy
Non-adherence to therapy should be considered in children and particularly adolescents with
poor metabolic control, especially in those presenting with recurrent diabetic ketoacidosis.
Medical regimens that are long-term, complex and that encroach considerably upon daily
living are less likely to elicit adherence.26
Higher levels of education in parents of children with diabetes and in adolescents with
type 1 diabetes are associated with improved adherence to therapy.27;28
Most children administer insulin assiduously. However, recommendations for diet,
physical activity, and self-monitoring of blood glucose (and hence self-adjustment of insulin
doses) are relatively neglected.29-33
Non-adherence is associated with deterioration in glycaemic control and increases the risk
of complications; however, the consequences of non-adherence are not sufficient to motivate
self-care behaviour.16;34
The NICE Guidelines for the Diagnosis and Management of Type 1 Diabetes in Children
and Young People have systematically reviewed the literature on non-adherence in diabetes
management.35 Non-adherence has typically been associated with adolescence36-39 as the
responsibility for maintaining an adequate diabetic regimen in younger children is often the
responsibility of parents.40
In a longitudinal study of school-age children with diabetes, serious non-adherence with
the medical regimen over nine years occurred in 45%.41 The initial episode of non-adherence
occurred at an average age of 14.8 years, while time spent being non-adherent was greatest
when the patients were aged between 17 and 19 years.41
At a time of increasing desire for autonomy, there may be conflict between parents and an
adolescent who desires independence and a sense of self-normality within peer groups.36;42
There appears to be a fine balance involved in the transfer of responsibility, with
significant problems in diabetes management occurring when self-care autonomy is promoted
or impeded at an inappropriate time.43
Psychiatric disorders may impact on blood glucose control by decreasing adherence with
medical requirements.17;41;44 In depression, the lack of motivation, loss of interest in daily
activities, and hopelessness may undermine the motivation to carry out tasks necessary to
maintain good glycaemic control.
Kovacs and colleagues (1992) found that 56% of children with psychiatric illnesses failed
to comply with their medical regimen, as compared to 17% of those without psychiatric
disorders.41
Psychological factors, such as low self-esteem, self-efficacy, and depressive symptoms,
have been found to account for 50% of the variance in treatment adherence.34
145
Intentional non-adherence, as opposed to non-adherence secondary to motivational or
attentional difficulties, is an area that is particularly problematic in individuals with type 1
diabetes exhibiting suicidal ideation or eating disorders. The rate of non-adherence to
treatment, which may be a form of self-destructive behaviour, rises from 25% to 63.3% when
suicidal ideation has been present in the past year.45
Adolescents with eating disorders are more likely to neglect the glycaemic monitoring,
and diet components of their treatment,46 and have also been found to omit or reduce insulin
dose in order to produce glycosuria as a method of weight control. 46;47;48
Risk Factors
Not all children with type 1 diabetes develop psychological difficulties. The following factors
have been studied for their impact on the development of psychological difficulties in
children with diabetes:
3;10
• Some studies report that females with diabetes are at greater risk,
while others have
failed to identify gender as a risk factor for psychiatric disorder.2;45
9;45;49
• Socioeconomic status is not predictive of psychological difficulties.
3
50
• Maternal psychopathology, conflictual or dysfunctional family environments and
5
avoidance coping behaviours have all been associated with poor psychological
adjustment to diabetes.
• Poor initial adaptation to diabetes is predictive of ongoing psychological
difficulties.8;9;51
• In the Australian longitudinal cohort study, children with behaviour problems at the
time of diagnosis were significantly more likely to have a DSM-IV psychiatric
diagnosis ten years later and to have had a history of chronic poor metabolic control.10
• A Victorian study on clinical and quality of life outcomes demonstrated lower quality
of life measures in rural youth with diabetes despite glycaemic control.
Treatments and Interventions
Effective care of children and adolescents with diabetes involves not only optimised medical
management, but also sensitive attention to psychological well being. The treatment regimen
should as simple and non-disruptive to lifestyle as possible, consistent with glycaemic targets.
Effective intervention with ‘at risk’ children is essential to prevent adverse physical and
mental health outcomes.
A Health Technology Assessment systematic review on the effects of educational and
psychosocial interventions for adolescents with diabetes found an overall small but positive
effect of interventions on HbA1c and psychosocial outcomes. However, as many of the
studies were small and different interventions were used, the need for larger high quality
RCT’s in this area is identified.52
Wysocki et al (2001)53 used Behavioral Family Systems Therapy (BFST) to teach
problem-solving and communication skills to adolescents and parents. When compared to
adolescents receiving standard, physician-directed treatment or those whose families had
attended groups focusing on education and social support, families involved in BFST showed
some improved parent-adolescent relations, and reduction in the amount and intensity of
family conflict.
Diabetes-specific conflict also decreased in the BFST group compared to the two control
groups. Interestingly, total glycated haemoglobin values increased throughout the study but
there were no significant between group or interaction effects on GHb at any measurement
point..
146
Several other groups have studied interventions promoting and maintaining family
involvement in diabetes management.54;55
54
• Anderson et al (1999) reported greater parental involvement in diabetes care and
significantly decreased diabetes-related conflict over time but no improvement in
glycaemic control.
55
• In contrast Laffel et al (2003) observed significantly improved diabetes control in the
treatment group compared to controls, but no improvement in health-related quality of
life or diabetes-related family conflict at one-year follow-up. Maintenance of, or an
increase in family involvement in diabetes management were comparable to those
found by Anderson et al (1999).54
Early research into promotion of personal and social coping skills reported promising
results for children and adolescents with diabetes.56;57
In a more recent and methodologically rigorous piece of research, group Coping Skills
Training (CST) was implemented as an adjunct to intensive diabetes management in
adolescents.58 The treatment group used role-plays focused on social situations that are
challenging for adolescents with diabetes, to develop social problem solving and conflict
resolution skills using cognitive behaviour modification principles. All groups reported a
decrease in HbA1c. Adolescents receiving intensive therapy plus CST reported better selfefficacy, less distress or difficulty in coping, and less impact of diabetes on quality of life in
comparison to the control group. One-year later both physiological and psychological
functioning had actually improved further.59 The level of distress or difficulty in coping was
the only factor where between-group differences dissipated over time.
Other studies also reported that diabetes-specific stress decreased over time in response to
the intervention, but metabolic control, regimen adherence, coping styles, and self-efficacy
about diabetes were unchanged.50;51
It is clear that no single intervention trialled to date results in improvement across all the
variables of interest, nor do psychological and physical health parameters always respond in
tandem. Further research is clearly needed, particularly with younger children and their
families.
The Evidence
The evidence for the incidence and risk factors for non-adherence in children and adolescents
with type 1 diabetes is listed in Evidence Table 13.1.
• Non-adherence with treatment regimens is common in children and adolescents with type
1 diabetes.16;27;28;30-34;36-39;41;45(IV)
36-39
• Non-adherence with treatment regimens is common especially during teenage years,
when an underlying psychiatric disorder is present,34;41;45 when the parents or child have a
low level of education,27;28 when self-care autonomy is promoted or impeded at an
inappropriate time,43 and when there is low level of cohesion within the family.27(IV)
• Adolescents have also been found to omit or reduce insulin doses in order to produce
glycosuria as a method of weight control.46;47;48(IV)
The evidence for the effects of psychosocial interventions on metabolic and psychological
outcomes in children and adolescents with type 1 diabetes is listed in Evidence Table 13.2.
• A Health Technology Assessment systematic review on the effects of educational and
psychosocial interventions for adolescents with diabetes found an overall small but
positive effect on HbA1c and psychosocial outcomes. However, as many of the studies
were small and different interventions were used, the need for larger high quality RCT’s in
this area is identified.52(I)
147
•
An RCT (n=119) comparing Behavioral Family Systems Therapy (BFST) with standard
treatment showed that BFST improved parent-adolescent relations and reduced family
conflict, but effects on glycaemic control were mixed.53(II)
• Another RCT (n=77) found the Coping Skills Training resulted in lower HbA1c and better
diabetes and medical self-efficacy, and less impact of diabetes on their quality of life (P
=0.005) than those receiving conventional management alone after 1 year.59(II)
• An RCT comparing family focused teamwork with standard care found significantly
improved diabetes control in the treatment group compared to controls, but no
improvement in health-related quality of life or diabetes-related family conflict was found
at one-year follow-up.55(II)
• Type 1 diabetes in childhood imposes a number of psychological stresses on both the child
and the family.1;35;60;61(C)
• Non-adherence with treatment regimens is common in children and adolescents with type
1 diabetes.16;27;28;30-34;36-39;41;45(IV)
36-39
• Non-adherence with treatment regimens is common especially during teenage years,
34;41;45
when an underlying psychiatric disorder is present,
when the parents or child have a
27;28
when self-care autonomy is promoted or impeded at an
low level of education,
inappropriate time,43 and when there is low level of cohesion within the family.27(IV)
• Health care professionals should be aware that adolescents may omit or reduce insulin
doses in order to produce glycosuria as a method of weight control.46;47;48(IV)
• Psychological interventions have been shown to improve HbA1c and psychosocial
outcomes.52;53;55;59(I)
I = Evidence from a systemic review of all relevant RCT’s
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Lavigne JV, Faier-Routman J: Psychological adjustment to pediatric physical disorders: a meta-analytic review. Journal of
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Grey M, Cameron M, Lipman T, Thurber FW: The relationship of initial coping behaviours to adjustment one year later in children
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Northam E, Anderson P, Adler R, Werther G, Warne G: Psychosocial and family functioning in children with insulin-dependent
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Wrigley M, Mayou R: Psychosocial factors and admission for poor glycaemic control: a study of psychological and social factors in
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Fonagy P, Moran GS, Lindsay MK, Kurtz AB, Brown R: Psychological adjustment and diabetic control. Archives of Disease in
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150
Long-term microvascular complications of diabetes can cause:
• Blindness due to diabetic retinopathy.
• Renal failure due to diabetic nephropathy.
• Disabling pain due to diabetic neuropathy.
Early microvascular changes are subclinical but can be detected by sensitive testing methods.
The most important antecedents for the development of microvascular complications in
children and adolescents are:
• Longer duration of diabetes.1
• Older age.1
• Poor glycaemic control.2
3
• Family history of diabetes complications.
The pubertal years accelerate the progression of microvascular complications of diabetes
(retinopathy, nephropathy and neuropathy). Hypertension,4-9 dyslipidaemia10-13 and
smoking14-19 influence the development of microvascular complications as well as
macrovascular complications.20
Discussing Complications
Families with a child or adolescent with diabetes should be made aware of the potential longterm complications of diabetes as part of their diabetes education.
This information should also be made gradually known to the adolescent at a rate
appropriate to his/her maturity and developmental stage.21
Young people need positive encouragement and education about complications during the
adolescent period.21
Improvements in diabetes control, no matter how small, all reduce the risk for the
development of microvascular complications.22;23
It is essential to emphasise that:
• Long-term good metabolic control reduces the risk of development and progress of
complications.2
• Outside of the normal range, there is no HbA1c threshold below which diabetes
complications will not occur.22;23
22;23
• For every degree of improvement in diabetes control a benefit is obtained.
These important facts can be used to motivate persons with diabetes to aim for gradual
improvements, no matter how small, in their diabetes control.
Screening for diabetes complications during adolescence reinforces this education process.
The threat of complications should not be made in trying to motivate adolescents or the
family to improve diabetes control.
Diabetic Retinopathy
Diabetic retinopathy is the fifth commonest cause of all blindness in Australia after
congenital causes.24 Diabetes is estimated to be the commonest cause of new blindness in
working age adults.25
151
The features of background retinopathy are:26
• Microaneurysms (the only specific feature of diabetic retinopathy).
• Haemorrhages (intraretinal and preretinal).
• Soft exudates (microinfarctions).
• Hard exudates (protein and lipid leakage).
• Intra-retinal microvascular abnormalities (IRMA).
• Dilatation, constriction and tortuosity of vessels.
Background retinopathy is not vision-threatening and may remain stable for years. It is an
almost universal finding in individuals with diabetes of over 20 years duration.
Microaneurysms are specific to diabetes and are not found in nondiabetic adolescents.27 They
may be transient, lasting from months to years.28
In some cases background retinopathy can progress to vision-threatening retinopathy which
includes:1;26;29;30
• Pre-proliferative retinopathy.
• Proliferative retinopathy.
• Maculopathy.
Pre-proliferative retinopathy is characterised by vascular obstruction, progressive IRMA and
infarctions of the retinal nerve fibre layer causing ‘cotton wool’ spots.
Proliferative retinopathy is characterised by the formation of new blood vessels
(neovascularisation) in the retina and/or vitreous posterior surface and is vision-threatening.
The vessels may rupture or bleed into the vitreoretinal space. Encasement in connective tissue
results in adhesions, which can cause haemorrhage and retinal detachment. High-risk
characteristics for visual loss are the location and extent of neovascularisation and signs of
vitreous or preretinal haemorrhage.31
In diabetic maculopathy, decreased vascular competence and microaneurysm formation
produce exudation and swelling in the central retina that can significantly decrease visual
acuity.
The most sensitive detection methods for retinopathy are:
• Stereoscopic fundal photography.
• Fluorescein angiography.
Stereoscopic fundal photography is at least twice as sensitive as direct ophthalmoscopy for
the less severe disease.32;33 Fundal photography (7-field) is comparable to two- field
fluorescein angiography in detecting retinopathy,34 however the latter requires intravenous
injection of fluorescein. Fluorescein commonly causes nausea and may cause anaphylactic
reactions.35 Fluorescein angiography reveals functional abnormalities (vascular permeability)
as well as structural abnormalities in the blood vessels whereas fundal photography reveals
only structural abnormalities. Both methods produce a recording (hard copy or electronic),
which can be referred to in subsequent assessments and can be shown to the adolescent.
Prevalence and association studies of retinopathy
The largest epidemiological study of diabetic retinopathy revealed the prevalence of any
grade of retinopathy to be:6
• 17% in those with less than five years diabetes duration.
• 50% after 5-6 years diabetes duration.
• 98% after 15 or more years duration.
152
Proliferative retinopathy was present in:6
• 4% after 10 years duration.
• 25% after 15 years.
• 67% after 35 years.
The frequency and severity of retinopathy were strongly associated with increasing diabetes
duration.6 The severity of retinopathy was also independently associated with increasing age.
Children less than 13 years of age had a lower prevalence of background retinopathy (9
percent) than those over 13 years (34 percent) with the same mean duration.36
In 1994, an Australian study of adolescents with type 1 diabetes showed that background
retinopathy was found in 42 percent (using stereoscopic fundal photography), with highly
significant associations with both total diabetes duration and glycaemic control.37 At a
median follow-up of 1.3 years, progression had occurred in 11% and regression in 5%.38
High blood pressure is a risk factor for the development and progression of retinopathy4;6;8
even after controlling for microalbuminuria.4
The evidence for an association of smoking with retinopathy is inconsistent.15;17;18;19;30;39
Higher cholesterol has been correlated with hard exudates and macular oedema10 and
lower HDL-cholesterol is associated with more retinopathy.12
Proliferative retinopathy is rare before 10 years of diabetes. In the Wisconsin study,
proliferative retinopathy, though rare, did occur in patients less than 20 years of age and, in a
few, as early as five years after diabetes.6
Screening for retinopathy
There is no evidence available to determine the optimal frequency for screening for
retinopathy in the paediatric and adolescent age group. One study is currently underway using
7-field stereoscopic fundal photography and thus data to answer this question may be
available soon. The current ISPAD recommendation is to screen for retinopathy annually in
adolescents after 2 years of diabetes and after 5 years of diabetes in those who are
prepubertal.21 The Canadian Guidelines 2003 recommend annual screening in those >15
years of age and after 5 years of diabetes.40 The NICE Guidelines do not offer a
recommendation for children and adolescents and recognise there is a diversity of views but
indicate that for adults with type 1 diabetes screening should start at diagnosis and be
performed annually.41
If stereoscopic fundal photography is used then biennial assessment may be appropriate
for those with minimal background retinopathy, diabetes duration of less than 10 years and if
the HbA1c is not significantly elevated. If significant retinopathy is present then more
frequent review is necessary.21;42
Immediate expert ophthalmological management should be sought if any of the following are
noted:42
• Progression of retinopathy to more than 10 microaneurysms.
• Moderate non-proliferative or preproliferative retinopathy.
• Visual change or deterioration, macular oedema or proliferative changes.
The ISPAD Consensus Guidelines 2000 recommend that assessment as a minimum should be
by ophthalmoscopy through dilated pupils by an observer with special expertise in diabetic
eye disease21 (pupil dilation by Cyclopentilate 1% + Phenylephrine 2.5% or Tropicamide 1%
± Phenylephrine 10%). Whilst the preferred method is by stereofundal retinal photography
through dilated pupils, the need for mydriasis is being investigated. Nonmydriatic retinal
photography may have a place in retinal screening in type 2 diabetes in which maculopathy is
153
a commoner form of sight-threatening disease. However, its place is not clear in type 1
diabetes which is characterised by proliferative, often peripheral, retinopathy as a cause of
sight-threatening disease. The Health Technology Board for Scotland assessment report43
states that there is no clear evidence that mydriasis or the routine use of more than one image
significantly alters the sensitivity or specificity of screening for the detection of sightthreatening retinopathy in adults. Comparable screening accuracy is achieved with digital
cameras, with or without mydriasis, however direct comparisons suggest that mydriasis may
occasionally result in a successful image when non-mydriatic imaging fails.43
Interventions to prevent or delay progression of diabetic retinopathy
The Diabetes Control and Complications Trial showed that intensive diabetes management
reduced the risk and progression of background retinopathy by 53% in adolescents.2 In the
adolescent cohort, vision-threatening retinopathy was too infrequent to allow comparison
between the intensive and conventionally managed groups.
In the subsequent four year follow-up after completion of the DCCT (EDIC-Epidemiology
of Diabetes Interventions and Complications), the intensive group continued to have a
reduction in significant progression despite a narrowing of the HbA1c difference between
intensively and conventionally treated groups (median 6.5 years of intervention).44 Laser
intervention was needed in 6% of the conventional group compared with 1% of the formerly
treated intensive group.44
Improved metabolic control may initially worsen diabetic retinopathy, however within 1.5 to
3 years; definite advantages of intensive treatment in these patients are evident.45-47
Intervention to improve glycaemic control is currently the only established therapy to
retard the progression of early retinopathy in adolescents. A randomised controlled trial in
adults showed reduction in progression of retinopathy with lisinopril (angiotensin converting
enzyme inhibitor) over a 2-year period in normotensive adults with type 1 diabetes.48
Randomised controlled trials using the older lipid-lowering drugs have shown a reduction in
retinal hard exudates.49-51
Large multicentre randomised trials in adults have shown that laser therapy reduces visual
loss from proliferative retinopathy.31;52 In at-risk eyes, timely laser intervention halves the
risk of blindness. Focal laser photocoagulation is beneficial in eyes with macular oedema.
Intervention needs to occur before clinical symptoms of visual loss.
Cataracts
The lens should be assessed, preferably by slit lamp examination, as specific stellate cataracts
can be seen in children after relatively short diabetes duration. On close questioning these
children often have symptoms suggestive of a prolonged antecedent history. The cataracts
can be vision-threatening and therefore may need excision.
Clinical examination of the eyes for the presence of cataracts should be performed soon
after diagnosis,21 especially if there has been a slow/prolonged onset of diabetes.53;54
Refractive Errors
Changes in blood glucose levels (e.g. during prolonged hyperglycaemia or more commonly
following stabilisation or initiation of treatment on diagnosis) can cause transient
accommodative problems. If there have been changes in glycaemic control, it is preferable to
delay the prescription of spectacles for 3 months.
154
Diabetic Nephropathy
Diabetic nephropathy is the second most common cause of end-stage renal disease in
Australia (after glomerulonephritis) and the commonest in New Zealand.55 Diabetic
nephropathy is also associated with premature death, generally due to associated
macrovascular disease.56;57
Persistent microalbuminuria has been shown to predict the development of clinical
diabetic nephropathy marked by gross proteinuria 6-14 years later.58-60 This progresses to
end-stage renal failure and is associated with increased risk of macrovascular disease.56;57
Albumin excretion rate can vary by as much as 40% for an individual so more than a
single sample is recommended when screening for renal disease.61
The definitions of microalbuminuria vary from centre to centre and include:
• Albumin excretion rate (AER) greater than 20 ug/min but less than 200 ug/min on a
minimum of two of three consecutive timed overnight urine collections.62
62
• Albumin/creatinine ratio (ACR) 2.5 - 25 mg/mmol (spot urine).
• (3.5 – 25 has been proposed in females because of lower creatinine excretion)
62
• Albumin/creatinine ratio (ACR) 30-300 mg/gm (spot urine).
62
• Albumin concentration (AC) 30-300 mg/L (early morning urine).
• In the DCCT microalbuminuria was defined as urinary albumin excretion greater or
equal to 40 mg per 24 hours (or 27.8µg/min) and less than 300 mg per 24 hours.63
Some groups have found that elevation at even lower levels predicts progression.64 In a
collaborative Australian study, a mean AER of 7.2 to 20µ g/min predicted progression to
microalbuminuria (four of six overnight urine specimens greater than 20µg/min) compared
with adolescents with a mean AER less than 7.2µg/min.65
Regression of microalbuminuria was documented in the DCCT and other studies. In an 8
year follow-up study of patients aged 15-44 years with microalbuminuria (defined as a mean
albumin excretion rate of 30-299 ug/min determined over the first two years), the six year
regression rate was 58% with progression to proteinuria only in 15%.66
Even using a definition of two of three abnormal timed collections for persistent
microalbuminuria, it has been recognised that regression back to normal can occur.67;68
Although an effect of duration has not always been demonstrated,69 the Oxford Regional
Prospective Study Group found that the cumulative probability for developing
microalbuminuria in children was 40% after 11 years of diabetes duration.70
Hypertension is generally established by the time of overt nephropathy. It remains
controversial whether blood pressure actually starts to rise during the transition from
normoalbuminuria to microalbuminuria or once microalbuminuria occurs. High blood
pressure is clearly associated with microalbuminuria. Mathiesen found the blood pressure to
rise only after microalbuminuria had occurred.71 In contrast, others have found that blood
pressure rose in parallel with the rise in AER.72 A cross sectional Australian study of
adolescents showed that ambulatory blood pressure measurements were already higher during
the phase of intermittent microalbuminuria compared to measurements in normoalbuminuric
adolescents.73 Longitudinal studies have shown that nocturnal hypertension74 and increased
ambulatory blood pressure75;76 precedes microalbuminuria.
Screening for nephropathy
The current ISPAD recommendation is to screen for microalbuminuria annually in:21
• Adolescents after 2 years of diabetes.
• Prepubertal children after 5 years of diabetes.
155
Screening should be by either:21
• Timed urine collections (preferably overnight).
or
• A spot urinary albumin/creatinine ratio.
The Canadian Guidelines 2003 recommend annual screening in postpubertal adolescents with
a duration of diabetes >5years or at the commencement of puberty and having a duration of
diabetes >5years.40 The NICE guidelines recognise the above diversity of views.41
Overnight timed collections are regarded as preferable as they avoid orthostatic and postexercise proteinuria. The spot or random albumin/creatinine ratios have the convenience of
ease of collection but are less sensitive for detecting rises within the normal range of albumin
excretion.
If microalbuminuria is found then screening should be more frequent, and other renal
investigations undertaken and specific focus should be placed on blood pressure
measurements.21 Implications of persistent microalbuminuria should be discussed with the
adolescent and the family.
Other factors that can cause microalbuminuria or lead to the false diagnosis of
microalbuminuria are:
• Glomerulonephritis.
• Urinary tract infection.
• Intercurrent infections.
• Menstrual bleeding.
• Vaginal discharge.
• Orthostatic proteinuria.
• Strenuous exercise.
Interventions to prevent or delay progression of diabetic nephropathy
The Diabetes Control and Complications Trial showed that intensive diabetes management
reduced the risk of developing microalbuminuria by 55% in adolescents in the secondary
intervention arm (with diabetes duration >5 years at entry).2 In the adolescent primary
prevention cohort, intensive diabetes management reduced the risk of developing
microalbuminuria by 10% percent. In the EDIC Study (the subsequent 4 year follow-up after
completion of the strict two treatment arms), the intensive group continued to have a
reduction in significant reduction in development of microalbuminuria (53%) and proteinuria
(86%).44
Effective antihypertensive therapy in patients with nephropathy (protein excretion >500
mg/ 24 hours or AER >200 ug/min) has dramatically prolonged the time to end-stage renal
disease from 7 to 21 years. Angiotensin Converting Enzyme Inhibitors (ACEI) slows the
decline in renal function more effectively than other antihypertensive agents.77;78 The
introduction of ACEI must be combined with monitoring of serum potassium and creatinine
concentrations. ACEIs are not licensed for use in pregnancy. If hypertension is not treated
effectively with ACEI alone, additional antihypertensives should be considered.
In normotensive patients with microalbuminuria, ACEI reduce urinary albumin
excretion;79 however a delay in progression to clinically overt nephropathy has not been
shown. They may in fact only mask the signs of the disease. Cessation of therapy has led to a
rapid increase in albuminuria similar to those in the placebo treated group.
The angiotensin II receptor antagonists are a relatively new class of drugs that are
promising and have a more specific effect on renoprotection than ACEI although to date most
large studies have been in adults with type 2 diabetes and nephropathy.80-82 Some reviews
156
indicate that they may also have a role in paediatric patients with diabetes and renal disease
although published studies are still awaited.83
Close attention to improving glycaemic control,2 cessation of smoking,16 care in
prescribing of OCP’s (see Chapter 18)14 and monitoring of lipids are important aspects in the
management of the patient with microalbuminuria.11
Lowering of the nutritional protein intake to decrease protein excretion in growing
children is not recommended, however excessive nutritional protein intake should be
discouraged (recommended maximum of 1.0-1.2 gm/kg body weight/day).21
Diabetic Neuropathy
Although clinical symptoms and signs of nerve disease in children and adolescents with type
1 diabetes are rare, studies have now demonstrated the presence of subclinical abnormalities.
The natural history of these subclinical findings is not yet clear; in particular, which
patients from this group progress to having more significant clinical abnormalities.
The presence of reduced sensation in the feet places the adolescent at increased risk of foot
problems and a referral for podiatric assessment is indicated.
Neuropathy needs to be considered in such situations as a child with recurrent vomiting
(possibly due to autonomic neuropathy) or persistent pain syndromes (possibly due to
peripheral neuropathy). The prepubertal child is not necessarily protected from risk.84
Peripheral neuropathy predisposes to foot ulceration and amputation. Painful peripheral
neuropathy can be disabling in young adults with childhood-onset diabetes85.
Autonomic neuropathy has been associated with an increased risk of sudden death (due to
hypoglycaemic unawareness or arrhythmia) and increased mortality.86
Screening for neuropathy
In adults with type 1 diabetes the consensus recommendation is for annual clinical evaluation
for the presence of peripheral nerve function. Clinical neuropathy is rare in children and
adolescents with type 1 diabetes even though prospective nerve conduction studies and
autonomic neuropathy assessment studies have demonstrated increased prevalence of
abnormal findings with greater duration of diabetes.21;87-90 Persistence of such abnormalities
is an inconsistent finding.87 With the exception of intensifying diabetes management no other
treatment is available. In the presence of poor diabetes control the following clinical
assessment should be undertaken:
• History, especially of numbness, pain, paraesthesia.
• Assessment of vibration sensation (by tuning fork or biothesiometer).
• Assessment of ankle reflexes.
• Assessment of sensation (by conventional neurologic examination or by graduated
filaments).
In addition, non-invasive tests of subclinical nerve function are available in some major
paediatric diabetes centres. These tests include:
• Autonomic nerve tests:
Heart rate response to deep breathing.
Heart rate response to standing.
Heart rate response to Valsalva manoeuvre.
Postural change in blood pressure.
Pupillary responses (dark adapted pupil size, rate of constriction and dilatation
following a flash of light).
• Peripheral nerve tests:
157
Vibration sensation threshold (using a biothesiometer).
Thermal discrimination thresholds.
Nerve conduction.
With all of the above tests of subclinical nerve function it is important that age- and genderspecific normal ranges are applied when interpreting results. The long-term implications of
finding early neuropathy are not yet established and apart from recommending improved
glycaemic control there is no proven specific therapy available.
Interventions to prevent or delay diabetic neuropathy
In the Primary Prevention Cohort of the DCCT, intensive therapy caused a 69% reduction in
the development of clinical neuropathy and in the Secondary Intervention Cohort a 56%
reduction.63 Clinical neuropathy was not sufficiently common for a significant effect to be
seen in the combined Adolescent Cohort (7/103 in the conventional group and 3/92 in the
intensive group).2
Aldose reductase inhibitors may have a place in the treatment of neuropathy91 but are not
yet available for clinical use.
Macrovascular Disease
Cardiovascular disease is the major cause of mortality in adults with type 1 diabetes. Clinical
macrovascular disease is rare under the age of 30 years. However, increased aortic and
carotid intima-media thickness has been detected by ultra-sensitive ultrasound in adolescents
with type 1 diabetes.92-94 Intensive therapy during the DCCT resulted in decreased
progression of intima-media thickness six years after the end of the trial.95
Even though macrovascular disease is not seen in type 1 diabetes in the childhood or
adolescent years, risk factors that predispose to it are frequently present, and adolescents and
their families should be aware of these:
• Hypertension.
• Dyslipidaemia.
• Smoking.
• Obesity.
• Microalbuminuria and diabetic nephropathy.
• Hypercoagulability.
• Family history of cardiovascular disease.
Hypertension
Blood pressure assessment in children and adolescents
Due to the pivotal role that blood pressure (BP) plays in the evolution of the microvascular
complications of diabetes, early and accurate diagnosis of hypertension is important to enable
early initiation of treatment where indicated.
Method for BP measurement
Blood pressure measurement needs to be accurate and reproducible. A variety of methods
exist to measure blood pressure, each of which has its strengths and weaknesses.
Irrespective of the method used, standardisation of the method of measurement is
important to reduce interobserver error. These include:
• Position of patient: for static measurement of BP, the patient should be seated quietly
for at least 5 minutes.
158
•
Blood Pressure Cuff Size: An appropriate selection of cuff sizes is required to ensure
that the bladder spans the circumference of the arm and covers at least 75% of the
upper arm without obscuring the antecubital fossa.
Sphygmomanometer
The sphygmomanometer is the most frequently used and least expensive method of BP
measurement. It is also the method most likely to result in readings with significant
intraindividual and interobserver variability. To reduce this problem the method of recording
BP should be standardised by:
• Readings should be taken in the right arm.
• The arm should be held at the level of the heart.
• The manometer should be positioned at the eye level of the person performing the
measurement to avoid parallax error.
• Initial cuff inflation should occur while manually palpating the radial pulse to estimate
systolic BP.
• The stethoscope should then be placed lightly over the brachial artery (excessive
pressure may create turbulence and confound results) and the cuff inflated to 20 mm Hg
above systolic pressure.
• Deflation should be at 2-3 mm Hg per second.
• Systolic blood pressure corresponds with the onset of the audible sound (K1 - the first
Korotkoff sound).
• As deflation of the cuff continues, the sounds will become muffled (K4) before
eventually disappearing (K5).
• Diastolic BP was previously taken as K4 in children less 13 years of age, and as K5 in
children greater than 13 years of age. The update on the 1987 taskforce report on high
blood pressure in children and adolescents, published in 1996 recommends the use of
K5 in all age groups even if Korotkoff sounds are audible down to 0 mm Hg.96
• 2 measurements should be made per visit with the mean systolic and diastolic BP taken.
• Results should be interpreted in light of age, gender and height specific centiles (Table
14.1).96
Dinamap
Static oscillometric blood pressure measurement devices are being used in increasing
numbers in the clinical setting. Although more expensive than the sphygmomanometer, they
provide reliable, reproducible readings and require minimal training. Issues of standardisation
of measurement technique and appropriate equipment use are the same as for measurements
with sphygmomanometer.
Studies that have compared this method of measurement with conventional
sphygmomanometry have obtained reasonable, although not perfect correlation97 for
population. Comparison for individuals may not correlate as well, although this will be
influenced by the degree of inter- and intraindividual variability that occurs with
sphygmomanometer measurements.
Single BP measurements with Dinamap can not differentiate ‘white coat hypertension’
(transient elevation of BP in a clinic setting) from persistent hypertension. The use of
multiple supine values is more effective because BP frequently falls with repeated
measurement. There are practical issues with this approach in the busy clinic setting.
Paediatric reference values
There are no studies that establish paediatric reference values using Dinamap. Studies that
employ static oscillometric devices frequently use reference data from the second taskforce
159
on BP in children, which may not be valid, given that systolic BP is higher and diastolic BP
lower with Dinamap measurements when compared with BP measurement using
sphygmomanometer.98;99
Ambulatory blood pressure monitoring
Ambulatory blood pressure monitoring provides more information than any other method of
BP measurement, and correlates best with the risk of hypertension-induced target organ
damage.100 Ambulatory blood pressure monitors use either an auscultatory or an oscillometric
method to measure blood pressure. The auscultatory method requires the use of a microphone
to detect the Korotkoff sounds. This method directly measures systolic and diastolic BP and
is more prone to false positive readings due to interference from environmental noise or
damage to the microphone. Oscillometric monitors are simpler, more robust, and not as prone
to false positive readings. They measure systolic and mean blood pressures directly and
calculate diastolic pressure. They are prone to the same variation as the Dinamap when
compared with sphygmomanometer readings. Most of the studies that have developed
reference ranges for ambulatory BP monitoring in children have used oscillometric monitors.
Advantages of ambulatory BP monitoring over other methods of BP measurement include:
• Ability to differentiate ‘white coat hypertension’, which may not pose the same risk of
morbidity as persistent hypertension.
• Ability to evaluate diurnal blood pressure variability - lack of nocturnal fall in BP is a
predictor of progression of diabetes complications.74
• Ability to determine blood pressure burden and more effectively determine
effectiveness of interventions.
• Better correlation with end organ damage.
• Simultaneous evaluation of heart rate variability, which may be an early marker of
autonomic dysfunction.
Disadvantages of ambulatory BP monitoring over other methods of BP measurement include:
• Cost - average ambulatory blood pressure monitors costs $2000-$4000 to purchase.
• Time consuming to staff and patient - which limits its usefulness as a screening tool.
• Monitoring disturbs sleep in some adolescents.
Paediatric reference values
Several large studies have established paediatric reference ranges for ambulatory BP
monitoring using oscillometric monitors101;102 although there are no large studies of this in an
Australian paediatric population. Systolic ambulatory BP correlates with height SDS, BMI
SDS, and heart rate SDS, whereas diastolic ambulatory BP correlates weakly with BMI SDS
only.101
Summary of blood pressure measurement methods
• Manual methods of BP measurement are most prone to measurement error although are
cheapest and have the most well-established reference ranges.
• Automated methods are simpler to use although values need to be interpreted carefully
given that they use a different method of measuring blood pressure.
• Ambulatory BP monitoring:
Provides the most detail.
Is useful for identifying borderline hypertension, and individuals with ‘white coat
hypertension’, in addition to establishing treatment effectiveness.
Is good at detecting early signs of autonomic neuropathy.
160
Is expensive and the time required to perform this technique mean that it is
frequently not used as a primary screening tool.
Age of screening for hypertension
Screening for hypertension should start at 3 years of age, although if the aim is to identify
hypertension resulting from non-diabetes related causes, measurement should start at
diagnosis of diabetes regardless of age, and continue at least annually if BP is less than 90th
centile for age and height.
When blood pressure reaches the 90th-95th centile, BP should be measured at least 6
monthly. If systolic and/or diastolic BP exceeds the 95th centile, measurements should be
performed at each visit, given that the diagnosis of hypertension requires persistent elevation
on three consecutive occasions.
Definition of hypertension
The US Task Force on BP control in children has defined hypertension as the average of
systolic and/or diastolic BP readings greater than or equal to the 95th percentile for age and
sex based upon measurements obtained on at least three occasions96 (Table 14.1). BP
readings between 90th and 95th percentiles are regarded as high normal BP and require close
and repeated monitoring.
In addition to height, age and gender, weight and parental hypertension are major
influences of BP.103 Family studies of patients with type 1 diabetes who develop nephropathy
commonly have non-diabetic parents who have essential hypertension, and also patients with
diabetes who have a family history of cardiovascular disease are up to 3 times more likely to
develop nephropathy.104
BP readings should be tracked longitudinally since even children without diabetes whose
BP is in the upper centiles are more likely to become hypertensive as adults.96 Nomograms,
based upon US data, are available for children that take into account age, gender and
height.105 Obesity can also result in significant increases in blood pressure.
Management of hypertension
All children with type 1 diabetes who are discovered to have hypertension need investigation
to establish the cause. There are frequently clinical clues that direct investigations that may
include:
• Clinical examination to look for evidence of cardiac murmurs (coarctation) or renal
bruits (renal artery stenosis).
• ECG and echocardiographic assessment of left ventricular size and thickness (looking
for left ventricular hypertrophy).
• Fundoscopy looking for retinal changes of hypertension.
• Microscopy of urine for sediment and red cell content and morphology.
• Determination of urine protein excretion.
• Measurement of electrolytes, urea and creatinine.
• Other investigations which may be indicated based upon clinical findings may include:
Renal ultrasound.
DMSA renal scan.
Renin and aldosterone measurement.
Urinary catecholamine measurement.
• Drug treatment (see Interventions to prevent or delay progression of diabetic
nephropathy).
161
Table 14.1: Blood Pressure Ranges for Height Centiles
Boys
Systolic BP by
Height Centile
Girls
Diastolic BP by
Height Centile
Systolic BP by
Height Centile
Diastolic BP by
Height Centile
Age
(yrs)
Height
centile
BP
Centile
1
90th
94
98
102
50
53
55
97
100
104
53
54
56
95th
98
102
106
55
57
59
101
104
107
57
58
60
90th
100
105
109
59
61
63
100
103
106
61
62
64
95th
104
109
113
63
65
67
104
107
110
65
66
68
90th
104
108
112
65
67
69
103
106
109
65
67
69
95th
108
112
116
69
71
74
107
110
113
69
71
73
90th
106
111
115
69
72
74
106
109
112
69
70
72
95th
110
115
119
74
76
78
110
113
116
73
74
76
90th
109
113
117
72
74
77
110
113
116
71
73
75
95th
113
117
121
76
79
81
114
117
121
75
77
79
90th
112
117
121
74
76
78
114
117
120
74
75
77
95th
116
121
125
78
80
83
118
121
124
78
79
81
90th
117
122
126
75
77
80
118
121
124
76
78
80
95th
121
126
130
79
82
84
121
125
128
80
82
84
90th
123
127
131
77
79
81
121
124
127
78
79
82
95th
127
131
135
81
83
86
124
128
131
82
83
86
90th
128
133
136
81
83
85
122
125
128
79
80
82
95th
132
136
140
85
87
89
126
129
132
83
84
86
3
5
7
9
11
13
15
17
5%
50%
95%
5%
50%
95%
5%
50%
95%
5%
50%
95%
Adapted from: Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: A
Working Group of the NHBPEP. Pediatrics. 98(4):649-658.
162
Dyslipidaemia
There is no consensus about the optimum age at which screening for lipid abnormalities
should commence in children with diabetes.
The natural history of lipid disorders has not been clearly established in children with type
1 diabetes, although the adverse effects of poor glycaemic control and of puberty on the lipid
profile are known. Children with diabetes have been shown to have higher levels of total and
LDL cholesterol, HDL cholesterol and apolipoproteins A1 and B than their siblings106 or
controls without diabetes.107
Even with good glycaemic control and normal or increased HDL-C levels, adult patients
with type 1 diabetes are at increased risk of developing accelerated atherosclerosis. Type 1
diabetes is associated with a greater proportion of smaller, more atherogenic LDL particles,
than controls without diabetes. Oxidation108 and non-enzymatic glycation109 increase the
atherogenic risk of LDL particles, by interfering with their clearance.
Hypercholesterolaemia is a risk factor for atherosclerotic vascular disease in all adult
groups studied although children and adolescents have not been studied.
In adults with type 1 diabetes, interventions that lower LDL cholesterol to levels <2.8
mmol/l, lower triglycerides and raise HDL cholesterol result in a reduction in the number of
cardiovascular events.110
The American Diabetes Association recommends screening for lipid disorders on an
annual basis in adults and 5 yearly in children >12 years of age if initial values are considered
low risk.110;111
Another group recommends screening for dyslipidaemia within 6 months of diagnosis and
re-testing mid-puberty.112
In most Australian tertiary paediatric diabetes clinics, screening for lipid disorders starts in:
• Prepubertal children after 5 years.
• Pubertal or postpubertal children after 2 years.
Screening should include measurement of:
• Total cholesterol.
• LDL cholesterol.
• HDL cholesterol.
• Triglycerides.
This should ideally be performed following an overnight fast, given that reference values for
cholesterol subfractions have been established on fasting samples. For screening purposes,
random measurement of lipid levels is acceptable, although triglyceride levels may be higher,
which affects calculated LDL cholesterol levels.
Interventions for dyslipidaemia
There are no studies that have determined the age at which treatment should be initiated in
adolescents with type 1 diabetes and dyslipidaemia.
Interventions to be considered in adolescents with dyslipidaemia include:
• Intensive glycaemic control.
• Attempts to achieve a more normal weight if obese.
• Regular exercise.
• Low saturated fat intake (<10% of energy intake).
163
•
•
•
•
•
Low cholesterol diet (step 1 cholesterol intake <300 mg/day, step 2 cholesterol intake
<200 mg/day).
Statins.113
Nicotinic acid.114;115
Bile acid sequestrants.115
Fibroic acid derivatives.
Fibrates have been shown to lower the rate of carotid intima medial thickening in
asymptomatic hyperlipidaemic adults with type 1 diabetes.116 There is limited experience
with their use in children.
Combination of a statin and a fibrate may increase the beneficial effects on lipids but also
increases the risk of adverse events including abnormal liver function tests, rhabdomyolysis
and myositis.110
Hypercoagulablity
Diabetes is associated with hypercoagulability.
Low dose aspirin has been recommended for adults with diabetes. However, the American
Diabetes Association guidelines advise against its use in those under age 20 years because of
the increased risk of Reye Syndrome.110
Cost Issues
No studies were identified which addressed the costs associated with screening for and
treating of microvascular or macrovascular complications of type 1 diabetes in children and
adolescents. A few studies were identified that addressed these issues in adults in different
health care settings. These results may not be applicable to the Australian health care setting.
In 1996 the Diabetes Control and Complication Research Group (using a Monte Carlo
model system) concluded that intensive therapy (compared with conventional therapy) was
well within the range of cost-effectiveness considered to represent good value in the
American health care system.117 This model did not include future costs. Another analysis
based on the DCCT model did include future costs and concluded that intensive therapy is
even more cost effective when future costs are considered.118
A computer model analysis (from the Swiss health insurance payer perspective) found that
screening for microalbuminuria and retinopathy followed by appropriate treatment, were cost
saving, with reduction in cumulative incidence of end stage renal disease and blindness
respectively and an improvement in life expectancy for those with microalbuminuria.119
Whilst other computer model analysis agree that screening for nephropathy is cost
effective,120 some disagree.121
The Evidence
The evidence on the effect of intensive diabetes management on microvascular and
macrovascular complications in adolescents with type 1 diabetes is listed in Evidence Table
14.1.
• The Diabetes Control and Complications Trial confirmed the relationship between good
glycaemic control (HbA1c) and decreased incidence of microvascular and macrovascular
complications in both adults and adolescents.2;20;22;63;95(II)
164
No studies were identified specifically addressing the optimum frequency of screening for
microvascular complications of type 1 diabetes in children and adolescents, therefore the
recommendations for screening reflect current consensus guidelines.21;122(C)
macrovascular complications of type 1 diabetes in children and adolescents; therefore the
recommendations for screening reflect current consensus guidelines.110;111;122(C)
• Type 1 diabetes confers the risk of long-term diabetes microvascular
complications.2;20;63;95(II)
• Families with a child or adolescent with diabetes should be made aware of the potential
long-term complications of diabetes as part of their diabetes education. Adolescents
should be made aware at a rate appropriate to their maturity.21;122(C)
• Families with a child or adolescent with diabetes should be made aware that long-term
good metabolic control reduces the risk of development and progress of
complications.2;63(II)
• Families with a child or adolescent with diabetes should be made aware that other
modifiable risk factors for diabetic microvascular complications include higher blood
pressure, smoking and dyslipidaemia.2;63(II)
• Screening for retinopathy should be performed annually in adolescents after 2 years of
diabetes and after 5 years of diabetes in those who are prepubertal.21;122(C)
• Assessment for retinopathy should be by an observer with special expertise in diabetic eye
disease. If stereoscopic fundal photography is used then biennial assessment may be
appropriate for those with minimal background retinopathy, diabetes duration of less than
10 years and if the HbA1c is not significantly elevated. If moderately severe retinopathy is
present then more frequent review is necessary.42;122(C)
• Clinical examination of the eyes for cataracts should be performed soon after diagnosis,
especially if there has been slow or prolonged onset of diabetes.21;122(C)
• Screening for microalbuminuria should be performed annually in adolescents after 2 years
of diabetes and after 5 years of diabetes in those who are prepubertal. Assessment should
be either by timed overnight urine collections or a spot urinary albumin/creatinine ratio. If
microalbuminuria is found then screening should be more frequent, and other renal
investigations undertaken and specific focus should be placed on blood pressure
measurements.21;122(C)
• In the presence of poor diabetes control, clinical evaluation of peripheral nerve function
should occur annually and should as a minimum include:122(C)
History (especially of numbness, pain, paraesthesia).
Assessment of vibration sensation (by tuning fork or biothesiometer).
Assessment of ankle reflexes.
Assessment of sensation.
• Type 1 diabetes frequently results in accelerated atherosclerosis. Good glycaemic control
can decrease this risk.20;95(II)
• Blood pressure measurements should be recorded at diagnosis and, if normal, annually.
Hypertension should be considered to be present if repeated blood pressure levels are
>95th centile for age, gender and height specific normative data.122(C)
165
•
Screening for lipid disorders should begin within 6-12 months of diagnosis of diabetes,
and if normal should be performed every 5 years in prepubertal children and every second
year in pubertal children.110;111(C)
II = Evidence obtained from at least one properly designed RCT
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169
Lipodystrophy (Lipoatrophy and Lipohypertrophy)
Lipoatrophy is now seldom seen with the use of human insulin. Although recent case
reports1;2 describe lipoatrophy occurring in pump patients treated with lispro insulin, it is still
an uncommon side effect.
Lipohypertrophy is a frequent complication of insulin therapy. It is estimated to be present
in almost 30% of those with type 1 diabetes.3
Non-rotation of injection sites has been consistently reported as an independent risk factor
for lipohypertrophy.3;4 Not only is it unsightly but insulin may be absorbed erratically and
unpredictably from these areas.5
Necrobiosis Lipoidica Diabeticorum
These are well circumscribed, raised reddish lesions sometimes progressing to central
ulceration, usually seen on the pre-tibial region. The reported prevalence in children varies
from 0.06% to 10%.6;7 The aetiology is not clearly understood. Necrobiosis lipoidica
diabeticorum has been associated with underlying microvascular complications.8;9 A wide
variety of treatments in adults have been used over the years including: topical, systemic or
intra-lesional steroids, aspirin, cyclosporin, mycophenolate, becaplermin, excision and
grafting, laser surgery, hyperbaric oxygen, topical granulocyte-macrophage colonystimulating factor and photochemotherapy with topical PUVA.10-17 None has been proven
useful in controlled clinical trials and many of these treatments have significant side effects.
Limited Joint Mobility
Limited joint mobility is a common complication affecting about 30% of those with type 1
diabetes in childhood and adolescence.18;19 One study describes a decreased prevalence over
the last 20 years (from 31% to 7%) which may reflect improved glycaemic control.20
Limited joint mobility is demonstrated by opposing the palms in a ‘praying position’
which demonstrates inability to straighten interphalangeal and metacarpophalangeal joints,
sometimes associated with limited mobility of wrists, elbows, neck and spine.
Limited joint mobility is associated with microvascular complications in children and
adolescents21;22 as well as in adults.23-25 This condition is sometimes associated with
thickening of the skin.
Contractures are seen more often in patients with poor long-term diabetic control.21
Limited joint mobility in the feet may lead to secondary foot problems associated with
abnormal pressure areas.26;27;28;29
There is no satisfactory treatment for limited joint mobility.
Osteopenia
Osteopenia (low bone mineral density) may occur in children and adolescents with type 1
diabetes. Decreased bone mineral density has been documented in diabetic children soon
after the diagnosis of clinical diabetes30 and in those with longer diabetes duration.31;32 The
underlying mechanism is not well understood and the long-term clinical significance of this is
uncertain.
170
Impaired Growth and Development
Monitoring of growth and development and the use of percentile charts is a very important
part of ongoing care of children and adolescents with diabetes.
Increased height at diagnosis of type 1 diabetes has been frequently reported.33-36 The
precise mechanism for this and whether or not this increased height is maintained is unclear.
Some studies report that poorly controlled patients show a decrease in height standard
deviation score over the next few years, whilst better controlled patients maintain their height
advantage.34;36 Others have not shown this relationship with diabetic control.35
In a recent Australian study, children treated with modern regimens (diagnosed after 1990)
maintained their increased height better than children diagnosis before 1991.33 Although the
median HbA1c did not differ significantly, those diagnosed after 1990 had a significantly
higher number of insulin injections per day.
Poor gain of height and weight and late pubertal development (Mauriac syndrome) are
often seen in children with persistently poorly controlled diabetes. Insulin insufficiency,
coeliac disease and other gastrointestinal disorders should be considered in this setting. There
is no role for human growth hormone therapy in the poorly growing child with diabetes,
unless it is associated with documented growth hormone deficiency.
Once the child or adolescent has reached a satisfactory weight after diagnosis, excessive
weight gain may indicate excessive energy intake and this may be related to excessive
insulin. Excessive weight gain is more common during and after puberty.37 The Diabetes
Control and Complications Trial and other studies have described greater weight gain as a
side effect of intensive insulin therapy.38-40 As obesity is a modifiable cardiovascular risk
factor, careful monitoring and management of weight gain in diabetes should not be
overlooked.
As large doses of insulin are required during the adolescent growth spurt, it is important to
remember to reduce the dose, if possible, as adult height is approached.
Associated Autoimmune Conditions
Hypothyroidism
Primary hypothyroidism due to autoimmune thyroiditis occurs in approximately 3-5 percent
of children and adolescents with diabetes. Antithyroid antibodies have been shown to occur
in up to 25% of individuals with diabetes,41-44 but are not necessarily associated with
hypothyroidism. Screening of thyroid function by Thyroid Stimulating Hormone (TSH) every
two years is recommended in asymptomatic individuals without a goitre or in the absence of
autoantibodies.45;46 More frequent assessment is indicated otherwise.
Clinical features may include the presence of a painless goitre, increased weight gain,
decreased growth, tiredness, lethargy, cold intolerance and bradycardia. Diabetic control may
not be significantly affected.
Hypothyroidism is confirmed by demonstrating a low free thyroxine and a raised TSH.
Compensated hypothyroidism may be detected in an asymptomatic individual with a normal
thyroxine level and a modestly raised TSH.
The treatment is oral L-thyroxine (T4) replacement sufficient to normalise TSH levels and
usually this allows regression of the goitre if present.
Hyperthyroidism
Hyperthyroidism is less common than hypothyroidism in association with diabetes,43;47 but
still more common than in the general population. It may be due to Grave’s disease or the
hyperthyroid phase of Hashimoto’s thyroiditis.
171
Hyperthyroidism should be considered if there is unexplained difficulty in maintaining
glycaemic control, weight loss without loss of appetite, agitation, tachycardia, tremor, heat
intolerance, thyroid enlargement or characteristic eye signs.
Treatment is anti-thyroid drugs such as carbimazole or propylthiouracil. Beta-adrenergic
blocking drugs are helpful during the acute phase of thyrotoxicosis to control tachycardia and
agitation. Treatment options for persistent or recurrent hyperthyroidism include surgery or
radio-active iodine.
Coeliac disease
Coeliac disease occurs in 1-10% of children and adolescents with diabetes.48-54 Recent
Australian paediatric studies have shown prevalence rates of 2.6-5.7% in diabetes clinic
populations.55;56 Coeliac disease is often asymptomatic52;54;57 and not necessarily associated
with poor growth or poor diabetes control (although it should be considered in these
situations). Any child with gastrointestinal signs or symptoms including diarrhoea, abdominal
pain, flatulence, dyspeptic symptoms, recurrent aphthous ulceration, unexplained poor
growth or anaemia should be investigated. Undiagnosed coeliac disease has also been
associated with increased frequency of hypoglycaemic episodes and a progressive reduction
of insulin requirement over the 12 months prior to diagnosis.58
Screening by immunological tests
At present there are no clear data regarding how frequently coeliac disease should be
screened for. Current consensus recommendations suggesting screening (by looking for the
presence of antiendomysial antibodies (EMA) or antigliadin antibodies when EMA is not
available) should be carried out around the time of diagnosis and every 2-3 years
thereafter46;59;60 or if the clinical situation suggests the possibility of coeliac disease.45 This
may need to be revised when more data are available.
IgA deficiency (which is present in 1: 500 people) should be excluded when screening for
coeliac disease by measuring the total IgA level. EMA IgA may not be detected in IgA
deficiency, resulting in a false negative test. If the child is IgA deficient, then IgG antigliadin
should be used for screening. It is important to remember that coeliac disease is more
common in those with IgA deficiency than in the general population (1.7% compared with
0.25%).61
Although experience with a recently introduced assay for tissue transglutaminase (tTG)
antibodies suggests that tTG may be more sensitive than EMA (91% vs 86%), the latter is
slightly more specific for coeliac disease (100% vs 96%).62 If EMA or tissue
transglutaminase antibodies are not available, then IgA antigliadin or IgG antigliadin (in the
<2-year-old child) antibodies are sensitive but less specific screening tests (than EMA) for
coeliac disease.
Follow up of positive antibody tests
In the presence of an elevated antibody level, a small bowel biopsy is needed to confirm the
diagnosis of coeliac disease (by demonstrating subtotal villus atrophy).
Treatment
A gluten-free diet normalises the bowel mucosa and frequently leads to disappearance of
EMA but may not lead to improved diabetic control. In an asymptomatic child with proven
coeliac disease the justifications for a gluten-free diet are to reduce the risk of subsequent
gastrointestinal malignancy and conditions associated with subclinical malabsorption
(osteoporosis and iron deficiency). Whilst this is a prudent recommendation, there is no
literature documenting the long-term benefit of a gluten-free diet in asymptomatic children
172
diagnosed with coeliac disease by routine screening. One paediatric case series has shown an
increase in height-for-weight following the introduction of a gluten-free diet.57 Another
demonstrated a non-significant increase in BMI and a non-significant reduction in HbA1c.63
Some studies have demonstrated short term benefits in other patient groups in terms of
improved wellbeing and increased bone mineral density.64-66 Another study demonstrated that
bone mineral density was already significantly decreased at the time of diagnosis of coeliac
disease in truly asymptomatic adults.67
A Swiss population based study found the risk of enteropathy associated T-cell lymphoma
to be low (0.07/100,000 per year). None of the 10 patients identified suffered from type 1
diabetes.68
Children with proven coeliac disease should be referred to a paediatric gastroenterologist
and receive support from a paediatric dietitian with experience in gluten-free diets.
Vitiligo
Vitiligo is an acquired, pigmentary disorder characterised by a loss of melanocytes resulting
in white spots or leukoderma.69 It is a common autoimmune condition associated with type 1
diabetes and is present in about 6% of diabetic children.7 Treatment is difficult and multiple
therapies have been tried with little success.
Oedema
Generalised oedema due to water retention is a rare complication of insulin therapy. Oedema
may be seen during establishment of glycaemic control after prolonged periods of poor
glycaemic control, particularly if there has been significant omission of insulin.70;71 The
oedema spontaneously resolves over a period of days to weeks with continued good
glycaemic control.
Primary adrenal insufficiency (Addison's disease)
Up to 2% of patients with type 1 diabetes have detectable antiadrenal autoantibodies.41;72;73
Addison’s disease is occasionally associated with type 1 diabetes (Autoimmune
Polyglandular Syndrome, APS I or II).
The condition is suggested by the clinical picture of:
• Frequent hypoglycaemia.
• Unexplained decrease in insulin requirements.
• Increased skin pigmentation.
• Lassitude.
• Weight loss.
• Hyponatraemia and hyperkalaemia.
Diagnosis is by demonstrating a low cortisol response to a Synacthen test. Treatment with
glucocorticoid and mineralocorticoid is urgent and lifelong.
In asymptomatic children with positive adrenal antibodies detected on routine screening,
methods of follow up vary. A rising ACTH level suggest a failing adrenal cortex and the
development of primary adrenal insufficiency.
The Evidence
No studies were identified addressing the optimal frequency of screening for thyroid disease
and coeliac disease in children and adolescents with type 1 diabetes. Therefore the
recommendations for screening are based on current consensus guidelines.45;59
173
The evidence for the effect of a gluten-free diet in children and adolescents with type 1
diabetes detected to have coeliac disease on routine screening is listed in Evidence Table
15.1.
• Only two short-term studies were identified describing the effect of a gluten-free diet in
asymptomatic children and adolescents with type 1 diabetes who have been detected to
have coeliac disease on routine screening. One case series has shown an increase in
height-for-weight following the introduction of a gluten-free diet.57 Another case series
demonstrated a non-significant increase in body mass index and a non-significant
reduction in HbA1c following a gluten-free diet.63(IV)
• No long-term studies were identified showing the benefits of a gluten-free diet in children
and adolescents with type 1 diabetes who do not have symptoms of coeliac disease when
detected by routine screening.
• Monitoring of growth and development and the use of growth charts is a very important
part of ongoing care of children and adolescents with type 1 diabetes.45;59(C)
• Screening of thyroid function by Thyroid Stimulating Hormone (TSH) every 2 years is
recommended in asymptomatic individuals without a goitre or in the absence of thyroid
autoantibodies. More frequent assessment is indicated otherwise.45(C)
• Screening for coeliac disease should be carried out around the time of diagnosis and every
2-3 years thereafter. More frequent assessment is indicated if the clinical situation suggests
the possibility of coeliac disease.46;59;60(C)
• Although the benefits of a gluten-free diet have not been proven in those with type 1
diabetes detected to have coeliac disease on routine screening,57;63 these children should
be referred to a paediatric gastroenterologist and on confirmation of the diagnosis receive
support from a paediatric dietitian with experience in gluten-free diets.59;74(C)
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Journal of Dermatological Treatment 8:123-125, 1997
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adolescents with insulin-dependent diabetes mellitus. Pediatric Dermatology 11:310-314, 1994
Infante JR, Rosenbloom AL, Silverstein JH, Garzarella L, Pollock BH: Changes in frequency and severity of limited joint mobility
in children with type 1 diabetes mellitus between 1976-78 and 1998. Journal of Pediatrics 138:33-37, 2001
Garg SK, Chase HP, Marshall G, Jackson WE, Holmes D, Hoops S, Harris S: Limited joint mobility in subjects with insulin
dependent diabetes mellitus: relationship with eye and kidney complications. Archives of Disease in Childhood 67:96-99, 1992
Frost D, Beischer W: Limited joint mobility in type 1 diabetic patients: associations with microangiopathy and subclinical
macroangiopathy are different in men and women. Diabetes Care 24:95-99, 2001
Arkkila PE, Kantola IM, Viikari JS, Ronnemaa T, Vahatalo MA: Limited joint mobility is associated with the presence but does not
predict the development of microvascular complications in type 1 diabetes. Diabetic Medicine 13:828-833, 1996
Montana E, Rozadilla A, Nolla JM, Gomez N, Escofet DR, Soler J: Microalbuminuria is associated with limited joint mobility in
type I diabetes mellitus. Annals of the Rheumatic Diseases 54:582-586, 1995
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predictors of elevated plantar pressure in diabetes. Diabetes 40:513 A, 1991
Cavanagh PR, Ulbrect JS: Clinical plantar pressure measurements in diabetes: rational and methodology. The Foot 4:123-135, 1994
Fernando DJS, Masson EA, Veves A, Boulton AJM: Relationship of limited joint mobility (LJM) to abnormal foot pressures and
diabetic foot ulceration. Diabetes Care 14:8-11, 1991
Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger JR: Decreased bone mineral density and bone formation markers
shortly after diagnosis of clinical type 1 diabetes mellitus. Journal of Pediatric Endocrinology & Metabolism 14:525-528, 2001
Valerio G, Del Puente A, Esposito-del Puente A, Buono P, Mozzillo E, Franzese A: The lumbar bone mineral density is affected by
long-term poor metabolic control in adolescents with type 1 diabetes mellitus. Hormone Research 58:266-272, 2002
Gunczler P, Lanes R, Paz-Martinez V, Martins R, Esaa S, Colmenares V, Weisinger JR: Decreased lumbar spine bone mass and low
bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. Journal of Pediatric
Endocrinology & Metabolism 11:413-419, 1998
Donaghue KC, Kordonouri O, Chan A, Silink M: Secular trends in growth in diabetes: are we winning? Archives of Disease in
Childhood 88:151-154, 2003
Gunczler P, Lanes R: Poor metabolic control decreases the growth velocity of diabetic children. Diabetes Care 22:1012, 1999
Bognetti E, Riva MC, Bonfanti R, Meschi F, Viscardi M, Chiumello G: Growth changes in children and adolescents with short-term
diabetes. Diabetes Care 21:1226-1229, 1998
Holl RW, Grabert M, Heinze E, Sorgo W, Debatin KM: Age at onset and long-term metabolic control affect height in type-1
diabetes mellitus. European Journal of Pediatrics 157:972-977, 1998
Holl RW, Heinze E, Seifert M, Grabert M, Teller WM: Longitudinal analysis of somatic development in paediatric patients with
IDDM: genetic influences on height and weight. Diabetologia 37:925-929, 1994
Holl RW, Grabert M, Sorgo W, Heinze E, Debatin KM: Contributions of age, gender and insulin administration to weight gain in
subjects with IDDM. Diabetologia 41:542-547, 1998
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children with diabetes mellitus: report on two prospective multicentre studies, one cross-sectional, one longitudinal. European
Journal of Pediatrics 151:258-262, 1992
De Block CE, De Leeuw IH, Vertommen JJ, Rooman RP, Du Caju MV, Van Campenhout CM, Weyler JJ, Winnock F, Van
Autreve J, Gorus FK, The Belgian DR: Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1
diabetes. Clinical & Experimental Immunology 126:236-241, 2001
Holl RW, Bohm B, Loos U, Grabert M, Heinze E, Homoki J: Thyroid autoimmunity in children and adolescents with type 1
diabetes mellitus. Effect of age, gender and HLA type. Hormone Research 52:113-118, 1999
Kontiainen S, Schlenzka A, Koskimies S, Rilva A, Maenpaa J: Autoantibodies and autoimmune diseases in young diabetics.
Diabetes Research 13:151-156, 1990
Kordonouri O, Klinghammer A, Lang EB, Gruters-Kieslich A, Grabert M, Holl RW: Thyroid autoimmunity in children and
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Adolescents. 1998
Umpierrez GE, Latif KA, Murphy MB, Lambeth HC, Stentz: Thyroid Dysfunction in Patients With Type 1 Diabetes: A longitudinal
Aktay AN, Lee PC, Kumar V, Parton E, Wyatt DT, Werlin SL: The prevalence and clinical characteristics of coeliac disease in
juvenile diabetes in Wisconsin. Journal of Pediatric Gastroenterology & Nutrition 33:462-465, 2001
Calero P, Ribes-Koninckx C, Albiach V, Carles C, Ferrer J: IgA antigliadin antibodies as a screening method for nonovert coeliac
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Crone J, Rami B, Huber WD, Granditsch G, Schober E: Prevalence of Coeliac Disease and Follow-up of EMA in Children and
Adolescents With Type 1 Diabetes Mellitus. Journal of Pediatric Gastroenterology & Nutrition 37:67-71, 2003
De VI, Ghirlanda G, Gasbarrini G: Prevalence of coeliac disease in type I diabetes: a multicentre study. Acta Paediatrica
Supplement. 412:56-57, 1996
Hansen D, Bennedbaek FN, Hansen LK, Hoier-Madsen M, Hegedu LS, Jacobsen BB, Husby S: High prevalence of coeliac disease
in Danish children with type I diabetes mellitus. Acta Paediatrica 90:1238-1243, 2001
Not T, Tommasini A, Tonini G, Buratti E, Pocecco M, Tortul C, Valussi M, Crichiutti G, Berti I, Trevisiol C, Azzoni E, Neri E,
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clinical characteristics and response to gluten-free diet. Diabetic Medicine 15:38-44, 1998
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pattern of clinical presentation and of gluten-free diet on bone mass and metabolism in adult coeliac disease. Bone 18:525-530,
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screening. Lancet 354:744-745, 1999
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Lang-Muritano M, Molinari L, Dommann-Scherrer C, Schueler G, Schoenle EJ: Incidence of enteropathy-associated T-cell
lymphoma in celiac disease: Implications for children and adolescents with type 1 diabetes. Pediatric Diabetes 3:42-45, 2002
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Immunopathology 82:37-42, 1997
176
Children and adolescents with diabetes do not display the devastating foot problems seen in
older people with diabetes. However, structural and functional abnormalities known to
predispose adults with diabetes to plantar ulceration are already present in young people with
diabetes.
Young people with diabetes may present with potentially destructive foot changes include
deformity, plantar callus and high plantar pressure. Although these abnormalities are not
unique to diabetes they have been shown to contribute to soft tissue breakdown, ulceration
and even amputation in adults. Other structural changes such as soft tissue thickening and
limited joint mobility in the foot are specific complications of diabetes and have been found
to alter the mechanics of the foot leading to high plantar pressure and ulceration.
When any of these abnormalities is associated with the macrovascular and/or neuropathic
complications of diabetes their effect is potentially devastating.
The identification of potentially destructive foot problems in young people with diabetes is
not always simple for the clinician. General foot deformities such as hammer toes, hallux
abductovalgus and plantar callus are simple to detect clinically. Superficial skin lesions such
as interdigital maceration, heloma durum (corns), onychocryptosis (ingrown toenails) or
verrucae (warts) are also simple to detect clinically. However less obvious structural
abnormalities require closer inspection by the clinician. The clinical assessment process
should include checking for abnormalities, which may indicate that the individual has some
form of mechanical imbalance.
Deformity
Any of the following abnormalities may indicate a functional imbalance, which can result in
abnormal pressure changes on the plantar surface of the foot or abnormal pressure from
footwear:
• A significant leg length discrepancy - greater than 1cm.
• Genuvarum or genuvalgum - genuvarum is normal up to the age of 2, genuvalgum is
normal between 2 to 7 year olds.
• Internal or external knee position.
• Varus or valgus foot position - a small degree of valgus alignment is normal up to 7
years old.
• In-toeing or out-toeing.
• Abnormal shoe wear patterns – the heel should wear to the centre or slightly laterally,
the sole should show even wear and the upper of the shoe should not be deformed.
• Inadequate shoe fit – either too small or too large.
Studies by Barnett et al1 and Larsen2 found that the incidence of foot deformities and skin
lesions (including plantar callus) in young people with diabetes is higher than that found in
those without diabetes. Both these studies also found that young people with diabetes were
more likely to wear shoes that were too small.
Some of the lower limb abnormalities outlined above should lead to examination by a
podiatrist, orthopaedic surgeon, paediatrician or physiotherapist with experience in
biomechanical evaluation of children.
177
Plantar Callus
Two studies have shown that the incidence of plantar callus is higher in the young diabetic
population.1;2 A more recent study3 found that there was no significant difference in the
number of diabetic subjects who presented with callus compared to age and sex matched
controls. Although, in this study, the number of subjects affected with plantar callus was no
different, those with callus had significantly higher plantar pressure than those without.
Plantar callus and high plantar pressure have been strongly linked to plantar ulceration in
adults with diabetes.
Young people presenting with plantar callus should be monitored closely for any indication
of soft tissue damage. They should also be advised to see a podiatrist for general foot care
and/or possibly some form of orthotic device because:
• Plantar callus may indicate structural or functional abnormality in the foot.
• Plantar callus can increase plantar pressure.
• People with plantar callus should always be regularly monitored for soft tissue change.
High Plantar Pressure
In adults high plantar pressure is a reliable predictor of subsequent ulceration in diabetic
people. Although neuropathy is an essential part, it is now believed that high plantar
pressures are a major determinant for the development of these lesions.4-8
No significant difference in plantar pressure between young people with diabetes and nondiabetic controls has been detected.3 However those with plantar pressures two standard
deviations above the non-diabetic control mean may be at risk of future foot pathology.
Treatment should be instigated when high plantar pressure is detected. Treatment should be
instigated when high plantar pressure is detected. Effective and non-invasive pressure
reducing treatments have also been investigated. These include simple cushioning insoles,
orthoses or both in conjunction.3
Plantar callus may be present in some individuals but there are no clinical signs of high
plantar pressure. The only method of evaluating plantar pressure is by using pressure analysis
equipment. This equipment should be available at most high-risk foot clinics and diabetes
complications assessment clinics.
Plantar pressure is assessed using pressure analysis equipment. High plantar pressure may
damage underlying soft tissue. People with diabetes who have high plantar pressure should be
encouraged to have regular foot examinations.
Soft Tissue Changes
Skin changes in diabetes are similar to those found in scleroderma and the aging process.9;10
In essence these changes result in the loss of elasticity and anchoring fibrils and thickening of
the dermis.11;12 This predisposes plantar skin to injury from minor trauma.12 Qualitative and
quantitative examination of the skin has been undertaken in young people with diabetes.
Rosenbloom et al13 found that the skin on the dorsum of the hands appeared thick, tight and
waxy in some young people with diabetes. This prompted investigation of the skin on the sole
of the foot using ultrasonography but no thickening of plantar skin was noted when diabetic
subjects were compared to non-diabetic controls.14
Thickening of the plantar aponeurosis has been found to be associated with increased
forefoot plantar pressure and limited joint mobility in adults with diabetes.15;16
178
Plantar aponeurosis thickening (greater than two standard deviations above the nondiabetic control mean) has been detected by ultrasound in thirty-two per cent of young people
with diabetes.14 In this study, thickening of the aponeurosis was associated with limited
subtalar joint mobility, but not with high plantar pressure in these younger individuals. It is
possible that the soft tissue changes found in these younger patients may not have progressed
sufficiently to alter plantar pressure. However, these young people should be closely
monitored for any increase in plantar pressure. Features to note include:
• Changes in skin tone which may predispose the foot to damage from minor trauma.
• Reduced adipose tissue on the plantar surface of the foot which increases mechanical
stress on plantar skin.
• Increased thickness of the plantar aponeurosis which may be associated with higher
plantar pressure.
Limited Joint Mobility
Limited joint mobility in the feet of adults with diabetes increases plantar pressure, which in
turn leads to tissue breakdown and ulceration.4-6;17;18 High plantar pressures in adults with
neuropathy are uncommon when joint mobility is within normal range.7 The primary
determinant of high plantar pressures is limited joint mobility, and neuropathy is a secondary
phenomenon.4-6
Limited joint mobility has also been detected in the feet of young people with
diabetes.1;14;19 The foot joints affected include the ankle, subtalar, 1st metatarsophalangeal and
interphalangeal joints. Joint limitation particularly at the 1st metatarsophalangeal joints has
been shown to increase plantar pressure under the hallux, an area at great risk of developing a
plantar ulcer.3
Limited joint mobility at the 1st metatarsophalangeal joint is relatively simple to detect
clinically. Young people with less than 60° of dorsiflexion (in a weightbearing position)
should be suspected of having limited joint mobility and more in-depth investigations of
other foot joint motion and plantar pressure should be undertaken.
The Evidence
The evidence for the effect of type 1 diabetes on joint mobility in the feet of young people is
1;14;19
• Reduced joint mobility in the feet has been found in young people with diabetes.
( IV)
The evidence data for the management of high plantar pressure in adolescents with type 1
diabetes is listed in Evidence Table 16.2.
• The effects of orthosis, cushioning or both in combination were monitored in 17 diabetic
subjects with high peak plantar pressure and in 17 diabetic subjects with plantar callus;
reductions of up to 63% were achieved. Diabetic subjects who had not received any
interventions showed no significant change in peak plantar pressure.3(IV)
No studies were identified addressing the optimal frequency of screening for foot
complications in children and adolescents with type 1 diabetes. Therefore the
recommendations for screening are based on current consensus guidelines.20(C)
179
• Health care professionals should be aware that the structural and functional abnormalities
known to predispose adults with diabetes to plantar ulceration are already present in young
people with diabetes.1;14;19(IV)
• Young people presenting with plantar callus, or detected to have high plantar pressures or
limited joint mobility need to be monitored closely for foot complications.20(C)
• Orthosis, cushioning or both in combination may be used to treat high peak plantar
pressure.3(IV)
IV = Evidence obtained from case series, either post-test or pre-test and post test
Reference List
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73:151-153, 1995
Larsen K, Katz L, Nielsen B: Footwear and deformity in diabetic children's feet. The chiropodist 11:435-437, 1980
Duffin A, Kidd R, Chan A, Donaghue K: High plantar pressure and callus in diabetic adolescents. Journal of the American
Podiatric Medical Association 93:214-220, 2003
Cavanagh PR, Fernando DJS, Masson EA, Veves A, Boulton AJM: Limited joint mobility (LJM) and loss of vibration sensation are
predictors of elevated plantar pressure in diabetes. Diabetes 40:513 A, 1991
Cavanagh PR, Ulbrect JS: Clinical plantar pressure measurements in diabetes: rational and methodology. The Foot 4:123-135,
1994
Fernando DJS, Masson EA, Veves A, Boulton AJM: Relationship of limited joint mobility (LJM) to abnormal foot pressures and
diabetic foot ulceration. Diabetes Care 14:8-11, 1991
Masson EA: What causes high foot pressures in diabetes: how can they be relieved. The Foot 2:212-217, 1992
Veves A, Murray H, Young M, Boulton A: The risk of foot ulceration in diabetic patients with high foot pressure: a prospective
study. Diabetologia 35:660-663, 1992
Brik R, Berant M, Vardi P: The Scleroderma-Like Syndrome of Insulin Dependent Diabetes Mellitus. Diabetes/ Metabolism
Reviews 7:121-128, 1991
Goodfield M, Millard L: The skin in diabetes mellitus. Diabetologica 31:567-575, 1988
Braveman I, Yen A: Ultrastructural abnormalities of the microvasculature and elastic fibres in the skin of juvenile diabetics. Journal
of Invesigative Dermatology 82:270-274, 1984
Dowd P, Gaywood I, Kurtz A, Shipley M: Diabetic Sclerodactyly. British Journal of Dermatology 116:21, 1986
Rosenbloom A, Silverstein J: Connective tissue and joint disease in diabetes mellitus. Endocrinology and metabolism clinics of
North America 25:473-481, 1996
Duffin AC, Lam A, Kidd R, Chan AKF, Donaghue KC: Ultrasonography of plantar soft tissues thickness in young people with
D'Ambrogi E, Giurato L, D'Agostino MA, Giacomozzi C, Macellari V, Caselli A, Uccioli L: Contribution of plantar fascia to the
increased forefoot pressures in diabetic patients. Diabetes Care 26:1525-1529, 2003
Kidd R, Kidd R: The role of abnormal collagen synthesis in the pathomechnics of the diabetic foot: A re-evaluation of the paradism
of neuropathy in podiatric practice. Australian Podiatrist 97-101, 1993
Delbridge L, Perry P, Marr S, Arnold N, Yue DK, Turtle JR, Reeve TS: Limited joint mobility in the diabetic foot: relationship to
neuropathic ulceration. Diabetic Medicine 5:333-337, 1988
Mueller MJ, Diamond JE, Delitto A, Sinacore D: Insensitivity, limited joint mobility and plantar ulcers in patients with diabetes
mellitus. Physical Therapy 69:453-462, 1989
180
The maintenance of dental health and the prevention of dental disease is important for
children and adolescents with diabetes mellitus.
The assessment of dental health should be a part of the regular medical follow-up. The
overall dental management for children and adolescents with diabetes includes:
• Maintaining oral hygiene using all available cleaning techniques (brushing, flossing,
and using toothpastes and antibacterial rinses).
• Regular cleaning and scaling of teeth by the dentist.
• Dietary advice.
• In some cases, chlorhexidine rinses.
• In some cases, antibiotics.
Children and adolescents with diabetes should be referred early to a dental specialist, such as
a periodontist or paediatric dentist, if there are special periodontal or decay problems.
Assessment of dental health includes not just the teeth, but the whole mouth cavity. It
should be remembered that patients with type 1 diabetes, especially those with poor
metabolic control, have an increased risk of oral candida carriage.1;2 This may also be
associated with dryness of the mouth, a burning sensation and painful fissures in the mouth
and lips.1
Dental Caries
Sugary foods and poor toothbrushing promote formation of dental plaque on the surface of
the tooth. Acids made by plaque bacteria become trapped under the plaque and cause tooth
decay. Substances released from the surface of the dental plaque (eg bacterial
lipopolysaccharides) activate a destructive inflammatory response in the gingivae.
For the child and adolescent with good glycaemic control, dental caries is no more likely than
for those without diabetes.3
However, dental decay is increased in those with poor glycaemic control and this has been
attributed to:4
5
• Reduced amount of saliva in the mouth.
• High glucose content in the saliva.
Periodontal Disease
Diabetes is a risk factor for periodontal disease especially when metabolic control is poor or
when diabetes duration is long.6-9
Periodontal disease is a chronic, potentially progressive bacterial infection resulting in
inflammation and destruction of tooth-supporting tissues. Diabetes is associated with
increased incidence, greater progression and severity of periodontal disease.
The periodontal tissues are made up of the:
• Gingivae (gums).
• Ligament holding the tooth into the bone (periodontal ligament).
• Bone itself.
181
The point of attachment of the gingival tissues to the tooth is a shallow groove around the
neck of the tooth (gingival crevice). The gingival crevice needs to be kept clean if it is to stay
healthy. If dental plaque is left on the surface of the teeth adjacent to the dental crevice,
inflammation of the gingivae will occur (periodontal disease). In diabetes there are changes in
the small blood vessels of the gingiva and changes in the local immune response to plaque,
particularly the neutrophil response. These changes can increase the risk of periodontal
disease.
Periodontal disease includes:
• Gingivitis.
• Periodontitis.
In gingivitis:
• The gingivae become red, swollen and bleed easily.
• The infection damages the attachment between the teeth.
• The infection is typically painless and little attention is usually paid to it.
10
• Associated smoking is a major risk factor for periodontal disease and can accelerate
the onset of periodontitis in teenagers.
In periodontitis:
• Periodontitis is unusual in children and adolescents; gingivitis is far more common.
• Progression to periodontitis occurs when the gum margins lose their tight seal against
the surface of the tooth and a pocket is formed between the gum and the tooth. Such
pockets provide an ideal spot for the growth of bacteria and are hard to clean out. The
bacteria are typically gram-negative anaerobes including Porphyromonas gingivalis,
Prevotella intermedia, spirochaetes and occasionally the micro-aerophilic organism
Actinobacillus actinomycetemcomitans.11
• Periodontitis is characterised by destruction of the gingiva, periodontal ligament,
alveolar bone, cementum and loss of connective tissue attachment.
• The gingivae may recede and the teeth begin to look longer (the recession may become
so severe that the teeth get very loose and need to be removed).
Gingivitis or more severe problems can be recognised just by looking and by gently probing
the gum margins to see if there is any bleeding or pocketing around the necks of the teeth.
Those with poor glycaemic control are more liable to gingivitis. If more detailed assessment
of the bone around the teeth is required then dental x-rays are used.
Prevention and Treatment of Dental Caries and Gingivitis
Tooth decay and gingivitis can be both prevented and/or reversed by:
• Using low fluoride or ‘Junior’ toothpaste (until 8 years of age), and daily use of a low
dose fluoride mouthwash to help repair any surface damage to the teeth.
• Regularly examining (twice yearly) for the presence of gingivitis or periodontal
disease.
• Taking extra care with dental hygiene in adolescents with orthodontic bands and wires
which make the cleaning of teeth very difficult and can exaggerate the gum response. In
this situation, the routine dental team should review more frequently for caries.
• Brushing and flossing teeth at least twice a day to remove the plaque from the surfaces
of the teeth and gingivae. Important points to note are:
182
The best brush is one with soft bristles and a small head and to use small circular
movements or short backward and forward vibration strokes.
Children seldom have the ability to perform efficient cleaning before the age 10
years and often the duration of their brushing is too brief.
Children also forget to clean the backs of their teeth and for these reasons parents
should brush young children’s teeth routinely.
With older children ‘parental brushing’ as often as possible is important.
The use of a battery-powered automatic toothbrush often improves a child’s
acceptance of this and increases the duration of brushing.
The Evidence
The evidence for the effect of type 1 diabetes on dental health in children and adolescents is
4
• Dental decay is increased in those with poor glycaemic control. (IV)
• Diabetes is a risk factor for periodontal disease especially when metabolic control is poor
or when diabetes duration is long.6-9( IV)
dental pathology in children and adolescents with type 1 diabetes; therefore the
recommendations for screening reflect current consensus guidelines.12(C)
• Children and adolescents with type 1 diabetes should be informed that dental decay is
increased when glycaemic control is poor.4(IV)
• Health care professionals should be aware that diabetes is a risk factor for periodontal
disease especially when metabolic control is poor or when diabetes duration is long.6-9(IV)
• Children and adolescents with type 1 diabetes should be informed that tooth decay and
gingivitis can be prevented and/or reversed by brushing and flossing teeth at least twice a
day to remove plaque from the surfaces of the teeth and gingivae.12(C)
• The mouth should be examined regularly (twice a year) for the presence of gingivitis or
periodontitis.12(C)
IV = Evidence obtained from case series, either post-test or pre-test and post test.
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
Bai KY, Reddy CD, Abu-Talib SH: Oral candidal carriage in young insulin dependent diabetics. Journal of the Indian Society of
Pedodontics & Preventive Dentistry 13:20-23, 1995
Hill LV, Tan MH, Pereira LH, Embil JA: Association of oral candidiasis with diabetic control. Journal of Clinical Pathology
42:502-505, 1989
Iughetti L, Marino R, Bertolani MF, Bernasconi S: Oral health in children and adolescents with IDDM--a review. Journal of
Pediatric Endocrinology & Metabolism 12:603-610, 1999
Twetman S, Johansson I, Birkhed D, Nederfors T: Caries incidence in young type 1 diabetes mellitus patients in relation to
metabolic control and caries-associated risk factors. Caries Research 36:31-35, 2002
Moore PA, Guggenheimer J, Etzel KR, Weyant RJ, Orchard T: Type 1 diabetes mellitus, xerostomia, and salivary flow rates. Oral
Surgery, Oral Medicine, Oral Pathology, Oral Radiology, & Endodontics 92:281-291, 2001
Miralles-Jorda L, Silvestre-Donat FJ, Grau Garcia-Moreno DM, Hernandez-Mijares A: Buccodental pathology in patients with
insulin-dependent diabetes mellitus: a clinical study. Medicina Oral 7:298-302, 2002
Pinson M, Hoffman WH, Garnick JJ, Litaker MS: Periodontal disease and type I diabetes mellitus in children and adolescents.
Journal of Clinical Periodontology 22:118-123, 1995
Marin N, Loyola-Rodriguez JP, Valadez-Castillo FJ, Hernandez-Sierra JF, Jesus Pozos-Guillen A: Effect of metabolic control in
diabetes mellitus type 1 patients and its association with periodontal disease. Revista de Investigacion Clinica 54:218-225, 2002
183
9.
10.
11.
12.
Takahashi K, Nishimura F, Kurihara M, Iwamoto Y, Takashiba S, Miyata T, Murayama Y: Subgingival microflora and antibody
responses against periodontal bacteria of young Japanese patients with type 1 diabetes mellitus. Journal of the International
Academy of Periodontology 3:104-111, 2001
Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG, Machtei EE, Norderyd OM, Genco RJ: Assessment of risk for periodontal
disease. I. Risk indicators for attachment loss. Journal of Periodontology 65:260-267, 1994
Sakamoto M, Takeuchi Y, Umeda M, Ishikawa I, Benno Y: Application of terminal RFLP analysis to characterize oral bacterial
flora in saliva of healthy subjects and patients with periodontitis. Journal of Medical Microbiology January 52:79-89, 2003
184
Introduction
Adolescents often struggle to cope with the demands of diabetes care. Adolescence is a time
when major physiological changes occur leading to increased insulin resistance. Insulin
dosages are typically higher during adolescence and most teenagers need to switch to a
multiple injection regimen.1 The DCCT demonstrated that HbA1c levels were generally 1%
higher in adolescents, both in the intensively treated and in the conventionally treated groups
but despite this had a higher prevalence of severe hypoglycaemia.2;3. Young people with type
1diabetes need to maintain and develop self-esteem and independence at a time when
diabetes care itself is at its most challenging.
The major risks faced by adolescents with type 1 diabetes include:4
• Deterioration of glycaemic control (see chapter 6).
• Risk-taking behaviour.
• Hypoglycaemia (see chapter 12)
• Recurrent diabetic ketoacidosis (see chapter 9).
• Accelerated microvascular complications (see chapter 14).
When managing adolescents with type 1 diabetes the aim is to achieve:
• Normal growth.
• Normal pubertal development.
• Normal psychological development.
1
• Maintenance of glycaemic control.
2;3
• Prevention of acute complications of diabetes (hypoglycaemia, diabetic
ketoacidosis5;6)
7
• Prevention or minimisation of microvascular complications.
• Normal lifestyle.
• Normal education opportunities.
• Avoidance of risk taking behaviours (smoking, substance abuse).
• Regular attendance to medical supervision.
• Comprehensive preparation for and transition to adult care.
An Approach to the Assessment of Adolescents
The HEADSS technique may be used (along with the routine medical history taking) to guide
the assessment of any adolescent.8 This comprehensive technique includes questions about:
• Home
• Education (or employment)
• Activities
• Drugs (also including alcohol and smoking)
• Sexuality (including contraception)
• Suicide (including other mental health issues)
Transition to Adult Care
Adolescents with diabetes have specific health needs relating to the physical, emotional,
psychological and socio-cultural stages of adolescence.9 Adolescents are less likely to adhere
to prescribed care and have poor glycaemic control.10-13 The transition from a paediatric to an
185
adult service for the adolescent with diabetes is often difficult. The position paper on
transition prepared by the Society for Adolescent Medicine outlines principles for successful
transition including:14
• The need for services to be appropriate for both chronological age and developmental
attainment.
• Transitional programmes to be flexible enough to meet the needs of a wide range of
young people, health conditions and circumstances.
• Transitional programmes to be prepared to address common concerns of young people
including growth and development, sexuality, mood and other mental health disorders
and damaging behaviours.
• Transfer of care to be individualised to meet specific needs.
If the transition is not carefully managed the following consequences may occur:
13
• Non-adherence to insulin regimens.
• Lack of follow-up.
• Prolonged period of poor glycaemic control resulting in suboptimal health.
• Acceleration of microvascular complications.
• Loss of access to emergency advice.
Of the 7 studies identified which addressed the issue of transition to adult services for
adolescents with type 1 diabetes, 6 were surveys of the patient15-19 or their paediatrician,20
and one was a case series.21
An Australian survey of young people with type 1 diabetes found that 5.7% felt the
transfer should occur before the age of 17 years, 48.6% between 17-20 years, and 44.8% at
any stage up to 25 years of age.15 Overseas surveys reported the mean ages for transition
were:
18
• Canada 18.5 years.
21
• Finland 17.5 years.
16
• United Kingdom (Exeter) 15.9 years.
A study of transition processes in the Oxford region, UK, showed that the 2 year clinic
attendance (at least 6 monthly) fell from 98% pre-transfer to 61% post-transfer (p<0.0005)
and the attendance rate for the first appointment on transfer was only 79%.17 A Canadian
survey of transition mean age 18.5 years) revealed 21% would have preferred earlier transfer
whereas 65% felt they would have liked transfer later.18 After transfer 13% had no regular
contact with the adult service, 3% maintained contact with a family practitioner only while
the remainder had regular contact with either an endocrinologist in private practice or an
adult clinic.18 Thirty-three percent reported problems with the transition process. A delay of
more than 6 months between the last visit to the paediatric service and the first visit to the
adult service occurred in 27% and in 17% the transition process took more than a year.18
As none of the studies compared different models of transition, the following
recommendations for transition are largely consensus based.
The formal transition phase should occur at a time of relative stability in the adolescent’s
health and may be coordinated with other life transitions. A useful age at which transition
should take place is the end of high school or when the adolescent leaves school to join the
workforce, however the following factors need to be taken into account:
• The admission policy of the hospital if care is managed through a hospital-based
diabetes service (many now incorporate adolescent services allowing care to the age of
18 years, while others have an age limit of 13-14 years).
• The wishes of the adolescent.
186
•
•
•
Emotional maturity.
Physical maturity.
Presence of any coexisting medical, surgical or psychiatric disorders that may be more
appropriately managed through the paediatric service.
Ideally the transfer to an adult service should involve:
• A preparation phase (from 12 years) which should be:
Planned well in advance.
Organised by a special transition service.
Discussed with the adolescent and family progressively over several years and
supplemented with written information outlining the transition process and the
available options.
• A formal transition phase (16-18 years) which should be:
Directed to an adult diabetes specialist or a clinic with a special interest in young
adults with type 1 diabetes.
Facilitated by a visit to the adult service or by having the adult physician attend the
adolescent clinic if care is provided through a paediatric hospital-based diabetes
service.
Formally arranged with appropriate letters of referral and details of past history.
Accompanied by clear directions on which emergency service to contact in the
transition period.
• An evaluation phase (18-19 years) to follow-up and confirm that the transition has
taken place in a timely fashion and that continuing appointments have been arranged.
Career Options
In previous times, there were a number of career paths which people with diabetes were
discouraged from pursuing. However, with improved understanding and management of
diabetes there are now few occupations from which people with diabetes are excluded.
In recent years a number of cases of workplace discrimination against people with
diabetes mellitus have been successfully challenged in the courts.
However, it is still prohibited to enter professions in:
• The Australian defence forces.
• The full-time or volunteer fire brigade.
• The police force (currently under challenge).
• The aviation industry - commercial or private pilot licences.
(Note: An individual already employed in one of the above listed services prior to a diagnosis
of diabetes mellitus may be removed from active duties following diagnosis and placed in a
more administrative role within the service).
It is not advisable for people with type 1 diabetes to work at heights (because of the risk to
themselves and others if they are affected by hypoglycaemia.
Driving
In the first instance, adolescents with diabetes should discuss with their parents and medical
team the issue of driving. The importance of having a good knowledge about hypoglycaemia,
its treatment and prevention cannot be overemphasised. The adolescent must be made aware
that the combination of alcohol, with its potential to cause hypoglycaemia, and diabetes can
result in fatal accidents. The main hazard to driving is unexpected hypoglycaemia.
187
Results from a recent American survey of drivers revealed an increased incidence of
driving mishaps in drivers with type 1 diabetes.22 Driving performance is significantly
disrupted at relatively mild hypoglycaemia.23 A responsible attitude towards driving is
therefore essential.
Adolescents should be taught to do a blood glucose estimation immediately before
driving a car and to have rapidly absorbed carbohydrate (eg glucose tablets) readily
accessible and to take these at the first indication of hypoglycaemia.
When considering hypoglycaemia for licensing purposes the Road and Traffic
Authorities are concerned with severe episodes which may impair consciousness, awareness,
motor skills or result in abnormal behaviour. Each State and Territory has its own set of
regulations governing the issue of licences to people with diabetes and health care
professionals should acquaint themselves with the regulations applying in their State or
Territory.
The second edition of ‘Assessing fitness to drive: Guidelines and standards for health care
professionals in Australia’ produced by Austroads Inc. in 2001, and approved by all
Australian Driver Licensing Authorities makes the following statements in relation to
suitability of people with diabetes to drive:24
• If there is poor management of a diabetic condition, or poor compliance by a patient to
their specified treatment, then the patient with diabetes should be advised not to drive.
• Patients with diabetic retinopathy may drive if their vision meets the specified criteria;
regular review by an eye practitioner is required.
• Patients with type 1 diabetes may drive providing they meet the other criteria in the
book. Two yearly review is required but the physician may recommend a shorter
review period.
• Patients newly starting on insulin therapy should be advised to notify the driving
licensing authority of the condition and the treatment.
• Patients should not drive after admission to hospital for stabilisation of diabetes until
cleared by their primary health physician.
• Patients should not drive after a major hypoglycaemic episode or hypoglycaemic
episode whilst driving until cleared by a physician.
Patients should be made aware about the effects of their condition on driving and advised of
their legal obligation to notify the driver licensing authority where driving is likely to be
affected. As a last resort, practitioners may themselves advise the driver licensing authority.24
Individuals who wish to pursue licences other than for cars, light trucks (up to 8 tonnes
gross vehicle mass) and motor cycles, should make enquires to their nearest driver licensing
authority.
Risk Taking Behaviour
Smoking
Smoking should be actively discouraged in diabetes25 and the education process should be
commenced in paediatric services. The risk of morbidity and mortality among smokers with
type 1 diabetes is increased.26
Clinicians working with adolescents should use outpatient office visits as an important
‘teachable moment’ to prevent tobacco use.27 Brief interventions (taking 1-2 minutes to ask
about smoking and make some recommendations) can be effective and should involve the
following stages:
• Ask about smoking habit.
• Advise to consider quitting.
188
•
•
•
Assess level of addiction and what ‘stage of change’ they are at.
Assist by providing quitting strategies and supports.
Arrange follow-up.
Approximately 30 percent of teenagers show evidence of recent nicotine exposure (from
screening surveys using urinary cotinine) and the prevalence in adolescents with diabetes
does not differ.
Diabetes education needs to address the following issues:
28
• Smoking is deleterious to the health of all persons at any age.
• Medical evidence indicates that smoking has been implicated is an additional risk factor
for the appearance and progression of microvascular disease (retinopathy, nephropathy
and neuropathy) and of macrovascular disease.29
• Smoking is also associated with:
Hypertension.
Poorer glycaemic control.
Excess general morbidity.
Additional risks in pregnancy.
Increased risk of periodontal disease.
Alcohol
It is illegal for alcohol to be sold to or served to young people under the age of 18 years in
Australia. Proof-of-age identity cards are needed by young people wishing to purchase or be
served alcohol.
No studies have been reported on the effects of alcohol ingestion on adolescents with
type 1 diabetes. Several small studies have reported the effects of moderate amounts of
alcohol consumed in the evening in adults with type 1 diabetes (0.5-1.0 gm per kg body
weight, equivalent to 3.5-7 standard (10gm alcohol) drinks for a 70 kg person).30-32 One study
(0.75 gm/kg alcohol) reported lower post-prandial and morning fasting blood glucose to the
point of requiring treatment of hypoglycaemia in 5 out of 6 patients,32 while the other two
studies showed no effect.30;31 The effects of drinking larger quantities (‘binge drinking’) have
not been studied. However, this pattern of drinking is emerging as the dominant form
especially for young females.
Alcoholic drinks provide extra kilojoules (important if weight control is a problem) and the
potential to cause the following effects:
• May initially increase blood glucose.
• May increase plasma lipids.
• May increase ketone levels.
• May inhibit gluconeogenesis resulting in delayed hypoglycaemia.
The combination of alcohol-induced confusion and hypoglycaemia is a particularly
dangerous one. Reaction times during hypoglycaemia have been shown to be reduced during
hypoglycaemia.33
Adolescents with diabetes need to be warned about the dangers of alcohol as part of their
diabetes education. Consensus guidelines4;34 relating to alcohol consumption have advised the
following:
• Drink in moderation.
• Do not exceed recommended safe intakes (2 standard drinks for adult males, 1 standard
drinks for adult females (1 standard drink is equivalent to approx 10gm alcohol)).
189
•
•
•
•
•
•
•
Avoid binge drinking.
Avoid consuming alcohol on an ‘empty stomach’.
Drink low-alcohol beers or wine rather than spirits, fortified wines or spirits/soft drink
mixes.
Measure blood glucose levels regularly during and after consuming alcohol.
Eat carbohydrate foods while consuming alcohol.
Eat prescribed snacks/meals on time.
Measure blood glucose before going to bed, eat a bedtime snack and ensure BG is
greater than 8 mmol/L.
Drugs
The most commonly used substances with the potential for abuse are still tobacco and
alcohol. From the limited information available it would appear that adolescents with
diabetes are no more likely to experiment with or use drugs. A survey of adolescents (age 1020 years) in the US found that 10% had used a drug in the past (8% in the previous year).35
There is little published information on substance misuse and their effects in adolescents with
type 1 diabetes. In general substance use has the capacity to:
• Alter perception.
• Alter cognitive ability.
• Alter consciousness.
• Alter sensation.
• Decrease capacity to achieve glycaemic control.
• Decrease interest in achieving glycaemic control.
• Decrease interest in routines, injection and meal schedules.
• Increase risk of hypoglycaemia being ignored or misinterpreted.
• Reduce appetite and interest in food that may potentiate hypoglycaemia.
• In the case of marijuana, stimulate appetite (the ‘munchies’) with a craving for
carbohydrate.
A significant percent of adolescent drug use is likely to be intermittent, experimental or
recreational, and effects on diabetes and its management may be few. Regular drug use has
the potential of causing deterioration in diabetes control. Regular drug use does not generally
occur in isolation but in the context of other risk-taking behaviours, psychosocial distress and
peer group or family drug usage.
Sexuality
Impotence
Fear of impotence may be a concern for adolescent boys with diabetes. Impotence may be
caused by psychological or organic conditions.
Impotence due to organic reasons may occur in adults with diabetes of long duration as a
result of autonomic neuropathy affecting the nerve supply to the corpora cavernosa or as a
result of macrovascular disease of the aorta affecting the blood supply to the penis.
Increasing age, duration of diabetes and poor glycaemic control are risk factors for
erectile dysfunction.36 Impotence is rare in the adolescent age group and may well be
minimised or prevented by good glycaemic control.
Impotence due to psychological reasons needs to be treated by counselling and
reassurance.
190
Contraceptives
adolescent diabetes care, as young persons may not actively seek contraceptive advice. The
clinician should reassure the adolescent that confidentiality will be maintained. Ensuring
confidentiality, along with establishing empathy will create a more suitable environment to
explore contraception and related issues.
Oral contraceptive pill (OCP)
Low dose oestrogen-containing OCP preparations are not contra-indicated in adolescents
with type 1 diabetes but should be used with caution if there is:
• Uncontrolled hypertension.
• Dyslipidaemia (particularly hypertriglyceridaemia).
• Evidence of microvascular disease.
• Evidence of macrovascular disease.
In general OCP use is not advised in young women with micro- or macro-vascular disease.
The best choice of oral contraceptive pill for adolescents with type 1 diabetes is a low
dose oestrogenic-containing monophasic or triphasic preparations.37 The new gestodenecontaining OCPs may have some advantages in patients with type 1 diabetes as they have less
effect on lipid profiles and carbohydrate metabolism, as well as being less androgenic.
Young women with type 1 diabetes using OCPs should have an annual gynaecological
review that should incorporate expert advice on the most appropriate method of
contraception.
Intrauterine devices (IUDs)
Although IUDs are not ideal, particularly in a nulliparous female with type 1 diabetes, if this
is the only form of contraception that is suitable or tolerated, it is preferable to an unplanned
pregnancy. The newer IUDs appear to be effective and well tolerated in diabetic women.38;39
The risk of pelvic infection, while probably low with newer devices, is highest in:
• New users.
• Younger age groups.
• Those at risk of sexually transmitted disease.
• Women with poorly controlled diabetes.
Barrier methods (condom, diaphragm)
Condoms may be used both as a primary contraceptive method and, importantly, should
always be advised for additional protection against the risk of sexually transmitted disease
even when other contraceptive methods are employed.
Barrier methods may appear to be well suited to young women with diabetes due to their
lack of side effects. However, a high degree of motivation and compliance is required as
these methods may have higher failure rates.
Progestogen depot/implant
These are extremely effective forms of contraception. Their use is limited in all women by
their side effects. Although they are suitable for use in women with diabetes they should be
used with caution as lipid profiles may be altered.40
191
Diabetes and Pregnancy
Pregnancy in all women with type 1 diabetes should be monitored from the pre-conception
stage by an experienced multidisciplinary team of obstetrician, diabetologist, diabetes
educator and dietitian.
Adolescent girls with diabetes should be made aware of the extreme importance of a
planned pregnancy. Education should address effective contraception to avoid an unplanned
pregnancy. Pregnancy should only occur when the HbA1c is within or close to the nondiabetic
range because poor glycaemic control increases the risk of large babies as well as increasing
the risk of foetal malformations 2-10 fold with progressive elevation of the HbA1c.41-43
Furthermore pregnancy may accelerate the progression of microvascular complications44 and
the risk of hypertensive disease in pregnancy is increased.45;46
Eating Disorders
A systematic review of case-control studies in children and adults showed that the incidence
of anorexia nervosa in people with type 1 diabetes is not increased.47 However, adolescent
females with type 1 diabetes and anorexia nervosa have a significantly increased mortality
rate compared to patients with type 1 diabetes alone.48
A systematic review of case-control studies has shown that the incidence of bulimia
nervosa, ED-NOS (Eating Disorder - Not Otherwise Specified) and sub-threshold disorders
are significantly increased in female adults and children with type 1 diabetes. 47 Eating
disorders in males with diabetes have been less extensively investigated, but some studies
suggest that they may display high levels of unhealthy weight control behaviours and high
drives for thinness.49;50
Studies have found an increased level of retinopathy in patients with type 1 diabetes and
sub-clinical and clinical eating disorders.47;51;52
The diagnostic criterion of the DSM-IV (Diagnostic and Statistical Manual of Mental
Disorders criteria) recognises medication manipulation for the purpose of weight loss as a
behavioural disturbance associated with eating disorders.53 Intensive glycaemic control is
associated with weight gain,2 and this may be unacceptable to many adolescents. Intentional
reduction or omission of insulin induces glycosuria and ketonuria, and hence weight loss (socalled insulin purging).56 The incidence of insulin omission or misuse in females with type 1
diabetes is 12-15%.54;55 Insulin purging leads to poor glycaemic control and increased risk of
medical complications.57
Predictive signs of disordered eating include:58
• Poor glycaemic control.
• Frequent hospital presentations with diabetic ketoacidosis.
• Weight loss or weight cycling.
• Unhealthy attitudes toward weight and/or food.
• Falsification of blood glucose levels.
The co-existence of type 1 diabetes and eating disorders presents difficulties for the
management of the diabetes as well as for psychological treatment. One of the goals of
cognitive behavioural therapy for bulimia nervosa is to relax control over eating and this can
conflict with the nutritional aspect of diabetes management.57 Treatment of eating disorders
depends on the type and severity of the disorder, but should include medical, nutritional and
psychological therapy by an experienced multi-disciplinary team.58
192
The Evidence
The evidence comparing glycaemic control in adolescents and adults is listed in Evidence
Table 18.1.
• The DCCT demonstrated that HbA1c levels were generally 1% higher in adolescents, both
in the intensively treated and in the conventionally treated groups.2;3(II)
The evidence for current transition processes and outcomes for adolescents with type 1
diabetes moving to the adult care system is listed in Evidence Table 18.2.
• Seven studies addressing the issues of transition to adult services identified poor or
delayed post-transfer clinic attendance and frequent dissatisfaction with the transition
process.15-21(IV)
• A study of transition processes in the Oxford region, UK, showed that the 2 year clinic
attendance (at least 6 monthly) fell from 98% pre-transfer to 61% post-transfer (p<0.0005)
and the attendance rate for the first appointment on transfer was only 79%.17(IV)
The evidence for the effect of type 1 diabetes on driving performance is listed in Evidence
Table 18.3.
• Results from a recent American survey of drivers revealed an increased incidence of
driving mishaps in drivers with type 1 diabetes.22(IV)
• Simulated driving performance is significantly disrupted at relatively mild
hypoglycaemia.23(IV)
The evidence for eating disorders in type 1 diabetes is listed in Evidence Table 18.4.
• A systematic review of case-control studies has shown that the incidence of Anorexia
Nervosa in females with type 1 diabetes is not increased, however the incidence of bulimia
nervosa, ED-NOS (Eating Disorder - Not Otherwise Specified) and sub-threshold
disorders are significantly increased in female adults and children with type 1 diabetes.47
Adolescent females with type 1 diabetes and anorexia nervosa have a significantly
increased mortality rate compared to patients with type 1 diabetes alone.48(IV)
• Males with diabetes have high levels of unhealthy weight control behaviours and higher
drives for thinness than non diabetic controls.49;50
• The incidence of insulin omission or misuse in females with type 1 diabetes is 1215%.54;55(IV)
• Studies have found an increased level of retinopathy in patients with type 1 diabetes and
sub-clinical and clinical eating disorders.47;51;52(IV)
• Health care professionals should be aware that glycaemic control is more difficult in
adolescents with type 1 diabetes.2;3(II)
• Adolescents with diabetes have specific health needs relating to physical, emotional,
psychological and socio-cultural stages of adolescence.4;9(C)
• The major risks faced by adolescents with diabetes include deterioration of glycaemic
control, risk-taking behaviour, hypoglycaemia, recurrent diabetic ketoacidosis and
accelerated microvascular complications.4(C)
• The transition from a paediatric to an adult service for the adolescent with diabetes is often
difficult.15-21(IV)
14
• Ideally the transfer to an adult service should be comprehensive and should involve: (C)
193
A preparation phase which is planned well in advance by a special transition service
and the adolescent and family.
A formal transition phase to an adult clinic, with appropriate referral and clear
directions for the patient and family (eg in case of emergencies).
An evaluation phase.
Adolescents should be taught to do a blood glucose estimation immediately before driving
a car and to have rapidly absorbed carbohydrate (eg glucose tablets) readily accessible and
to take these at the first indication of hypoglycaemia.22;23(IV)
Smoking should be actively discouraged in diabetes.25(C)
Adolescents with diabetes need to be warned about the dangers of alcohol as part of their
diabetes education.59;60(C)
Issues surrounding sexuality should be approached with confidentiality and empathy.4(C)
adolescent diabetes care.4;59(C)
Health care professionals should be aware that the incidence of eating disorders is
increased in males and females with type 1 diabetes47;49;50 and that adolescent females with
type 1 diabetes and anorexia nervosa have a significantly increased mortality rate
compared to patients with type 1 diabetes alone.48(IV)
Health care professionals should be aware that intentional reduction or omission of insulin
to achieve weight loss is common (so-called insulin purging).54;55(IV)
Health care professionals should be aware that increased levels of retinopathy have been
found in patients with type 1 diabetes and sub-clinical and clinical eating
disorders.47;51;52(IV)
Treatment of eating disorders should include medical, nutritional and psychological
therapy by an experienced multidisciplinary team.57;58(C)
•
•
•
•
•
•
•
•
•
II = Evidence obtained from at least one properly designed randomised controlled trial
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Rosen DS, Blum RW, Britto M, Sawyer SM, Siegel DM, Society for Adolescent Medicine: Transition to adult health care for
adolescents and young adults with chronic conditions: position paper of the Society for Adolescent Medicine. Journal of Adolescent
Health 33:309-311, 2003
Court JM: Issues of transition to adult care. Journal of Paediatrics & Child Health 29:S53-S55, 1993
Eiser C, Flynn M, Green E, Havermans T, Kirby R, Sandeman D, Tooke JE: Coming of age with diabetes: patients' views of a clinic
for under-25 year olds. Diabetic Medicine 10:285-289, 1993
Kipps S, Bahu T, Ong K, Ackland FM, Brown RS, Fox CT, Griffin NK, Knight AH, Mann NP, Neil HA, Simpson H, Edge JA,
Dunger DB: Current methods of transfer of young people with Type 1 diabetes to adult services. Diabetic Medicine 19:649-654,
2002
Pacaud D, McConnell B, Huot C, Aebi C, Yale J: Transition from pediatric care to adult care for insulin-dependent diabetes
patients. Canadian Journal of Diabetes Care 20:14-20, 1996
Datta J: Transition to adult care. Moving up with diabetes. The transition from paediatric to adult care. London, NCB books, 2003
Jefferson IG, Swift PG, Skinner TC, Hood GK: Diabetes services in the UK: third national survey confirms continuing deficiencies.
Salmi J, Huupponen T, Oksa H: Metabolic control in adolescent insulin-dependent diabetics referred from pediatric to adult clinic.
Annals of Clinical Research 18:84-87, 1986
Care 26:2329-2334, 2003
Cox DJ, Gonder-Frederick LA, Kovatchev BP, Julian DM, Clarke WL: Progressive hypoglycemia's impact on driving simulation
performance. Occurrence, awareness and correction. Diabetes Care 23:163-170, 2000
Austroads: Assessing Fitness to Drive. Guidelines and Standards for Health Professionals in Australia. Sydney, Austroads
Incorporated, 2001
International Diabetes Federation. Position Statement. Diabetes and tobacco use: a harmful combination . 2003.
Gay EC, Cai Y, Gale SM, Baron A, Cruickshanks KJ, Kostraba JN, Hamman RF: Smokers with IDDM experience excess
morbidity. The Colorado IDDM Registry. Diabetes Care 15:947-952, 1992
Vickers KS, Thomas JL, Patten CA, Mrazek DA: Prevention of tobacco use in adolescents: review of current findings and
implications for healthcare providers. Current Opinion in Pediatrics 14:708-712, 2002
Doll R, Peto R, Wheatley K, Gray R, Sutherland I: Mortality in relation to smoking: 40 years' observations on male British doctors.
Sinha RN, Patrick AW, Richardson L, Wallymahmed M, MacFarlane IA: A six-year follow-up study of smoking habits and
microvascular complications in young adults with type 1 diabetes. Postgraduate Medical Journal 73:293-294, 1997
Koivisto VA, Tulokas S, Toivonen M, Haapa E, Pelkonen R: Alcohol with a meal has no adverse effects on postprandial glucose
homeostasis in diabetic patients. Diabetes Care 16:1612-1614, 1993
Moriarty KT, Maggs DG, Macdonald IA, Tattersall RB: Does ethanol cause hypoglycaemia in overnight fasted patients with Type 1
diabetes? Diabetic Medicine Vol.10(1):61-65, 1993
Turner BC, Jenkins E, Kerr D, Sherwin RS, Cavan DA: The effect of evening alcohol consumption on next-morning glucose
control in type 1 diabetes. Diabetes Care 24:1888-1893, 2001
Kerr D, Macdonald IA, Heller SR, Tattersall RB: Alcohol causes hypoglycaemic unawareness in healthy volunteers and patients
with type 1 (insulin-dependent) diabetes. Diabetologia 33:216-221, 1990
Diabetes UK. Information. Alcohol and Diabetes. 2003. London, Diabetes UK.
Prey MA, Guthrie B, Loveland-Cherry C, Pil SP, Foster CM: Risky behavior and risk in adolescents with IDDM. Journal of
Adolescent Health 20:38-45, 1997
Fedele D, Coscelli C, Cucinotta D, Forti G, Santeusanio F, Viaggi S, Fiori G, Velona T, Lavezzari M, Diade Study Group:
Incidence of erectile dysfunction in Italian men with diabetes. Journal of Urology 166:1368-1371, 2001
Alison Nankervis: Sexual Function and Pregnancy. In Diabetes and the Adolescent. 1 ed. George A Werther, John M Court, Eds.
Melbourne, Miranova Publishers, 113-136, 1998
Kimmerle R, Weiss R, Berger M, Kurz KH: Effectiveness, safety, and acceptability of a copper intrauterine device (CU Safe 300)
in type I diabetic women. Diabetes Care 16:1227-1230, 1993
Petersen KR, Skouby SO, Jespersen J: Contraception guidance in women with pre-existing disturbances in carbohydrate
metabolism. European Journal of Contraception & Reproductive Health Care 1:53-59, 1996
Diab KM, Zaki MM: Contraception in diabetic women: comparative metabolic study of Norplant, depot medroxyprogesterone
acetate, low dose oral contraceptive pill and CuT380A. Journal of Obstetrics & Gynaecology Research 26:17-26, 2000
Rosenn B, Miodovnik M, Dignan PS, Siddiqi TA, Khoury J, Mimouni F: Minor congenital malformations in infants of insulindependent diabetic women: association with poor glycemic control. Obstetrics & Gynecology 76:745-749, 1990
Ray JG, O'Brien TE, Chan WS: Preconception care and the risk of congenital anomalies in the offspring of women with diabetes
mellitus: a meta-analysis. Quarterly Journal of Medicine 94:435-444, 2001
Small M, Cassidy L, Leiper JM, Paterson KR, Lunan CB, MacCuish AC: Outcome of pregnancy in insulin-dependent (type 1)
diabetic women between 1971 and 1984. Quarterly Journal of Medicine 61:1159-1169, 1986
The Diabetes Control and Complications Trial Research Group.: Effect of pregnancy on microvascular complications in the
diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. Diabetes Care 23:10841091, 2000
Roach VJ, Hin LY, Tam WH, Ng KB, Rogers MS: The incidence of pregnancy-induced hypertension among patients with
carbohydrate intolerance. Hypertension in Pregnancy 19:183-189, 2000
Hanson U, Persson B: Epidemiology of pregnancy-induced hypertension and preeclampsia in type 1 (insulin-dependent) diabetic
pregnancies in Sweden. Acta Obstetricia et Gynecologica Scandinavica 77:620-624, 1998
Nielsen S: Eating disorders in females with type 1 diabetes: An update of a meta-analysis. European Eating Disorders Review
10:241-254, 2002
Nielsen S, Emborg C, Molbak AG: Mortality in concurrent type 1 diabetes and anorexia nervosa. Diabetes Care 25:309-312, 2002
Neumark-Sztainer D, Patterson J, Mellin A, Ackard DM, Utter J, Story M, Sockalosky J: Weight Control Practices and Disordered
Eating Behaviors Among Adolescent Females and Males With Type 1 Diabetes: Associations with sociodemographics, weight
concerns, familial factors, and metabolic outcomes. Diabetes Care 25:1289, 2002
195
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Svensson M, Engstrom I, Aman J: Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared
with healthy controls. Acta Paediatrica 92:114-117, 2003
Affenito SG, Backstrand JR, Welch GW, Lammi-Keffe CJ, Rodriguez NR, Adams CH: Subclinical and clinical eating disorders in
IDDM negatively affect metabolic control. Diabetes Care 20:182-184, 1997
American Psychiatric Association: Diagnostic and statistical manual of mental disorders - Fourth Edition (DSM - IV). Washington
DC, American Psychiatric Association, 1994
15:1356-1360, 1992
Crow SJ, Keel PK, Kendall MD: Eating Disorders and Insulin-Dependant Diabetes Mellitus. Psychosomatics 39:233-243, 1998
National Institute for Clinical Excellence. Eating Disorders: Core interventions in the treatment and management of anorexia
nervosa, bulimia nervosa, and related eating disorders. 2003. London.
Daneman D, Olmsted M, Rydall A, Maharaj S, Rodin G: Eating disorders in young women with type 1 diabetes. Prevalence,
problems and prevention. Hormone Research 50:79-86, 1998
196
Chapter 19: School
School attendance is compulsory for children from 6 to 15 years unless:
• Families lack access to an educational facility if geographically isolated.
• A medical condition or religious conviction prevents attendance.
All children and adolescents with type 1 diabetes should attend school and participate in
normal school activities. Diabetes should not be the cause of a child or adolescent being
excluded from any school activity. Full participation in all academic, social and sporting
activities is possible and should be encouraged. Any discrimination or stigmatisation is
unacceptable.
School is a major part of a child’s life and needs to be a rewarding experience. It is
important for children to enjoy school and to function well at school because during the
school term they spend approximately 40 percent of their waking hours there.1 School
achievement and adjustment to school are important indicators of the child’s general
wellbeing. Furthermore, development of self-esteem and confidence in school activities is
likely to have positive effects on diabetes management. Conversely, school difficulties are
likely to impact negatively on diabetes control. Behavioural problems at school may be
totally unrelated to the child’s diabetes and should not be dismissed as due to diabetes alone.
Children with chronic illness are more at risk for school absenteeism and dysfunction than
their healthy peers.2;3
School personnel need to be provided with sufficient information to enable them to provide a
classroom environment which facilitates the child’s full integration by ensuring or
facilitating:
• Safety at all times.
• Attainment of developmental goals (by exposure to normal life experiences).
• Development of self-esteem.
• Freedom from discrimination from staff and students.
• Peer acceptance and understanding.
It is a legal requirement that schools provide a safe environment conducive to learning and
social development in all children, including those with special health needs. Students with
diabetes may require additional care. The school has a duty of care to all children including
those with special needs. Parents and caregivers of children and adolescents with diabetes
should work cooperatively with the school system to ensure mutual understanding of the
extent of care provided. With appropriate training some teachers may volunteer to supervise
or carry out blood glucose testing, insulin administration or glucagon administration.
It is important that all staff, including relief staff, have sufficient knowledge about diabetes
to ensure the safety of students with diabetes (especially in regard to hypoglycaemia and
safety in sport).
An individualised Diabetes Health Care Plan, especially for the younger child with
diabetes, should be developed by the parents/care-givers, the student’s health care team and
the school.4
Specific responsibilities in the Care Plan need to be understood and accepted by
parents/care-givers as well as the school.
In some states, for very young children with unstable diabetes, an application can be made
to the Department of Education for additional supervision (‘integration support’) in the
school setting.
Chapter 19: School
197
The diabetes management should cause as little disruption as possible, provided that
metabolic control and avoidance of hypoglycaemia are not compromised.
General Considerations in the Development of the Care Plan
Many children’s diabetes centres and some diabetes associations provide school visits by
diabetes educators to inform the staff of the details they need to know about diabetes and to
answer any specific questions. The value of these visits cannot be over-estimated and all
teaching and office staff should attend. Priority should be given to younger children
especially those attending long day care and pre-school.
Diabetes Australia in some States provides a ‘Schools Care Line’. This is a telephone
service, manned by a paediatric diabetes educator, available to teachers, parents and students.
Essential information (for example the IDF School Pack, accessible from
www.diabetesnsw.com.au) for school personnel is available from diabetes centres, Diabetes
Australia, Juvenile Diabetes Research Foundation (JDRF) and community health centres. All
school personnel (including relief staff and after-school care staff) should be informed if a
child in their care has type 1 diabetes. It may be helpful for relief staff to have photographic
identification of any child with diabetes in their care.
Background information on diabetes provided to schools should include:
• Differences between type 1 and 2 diabetes.
• Provision of basic information on hypoglycaemia including:
Recognition of hypoglycaemia symptoms.
Treatment protocols for mild to moderate hypoglycaemia. Awareness that repeat
treatment may be necessary.
Awareness of the transient deterioration in the child’s brain function and behaviour
during and following a hypoglycaemic episode.
Basic first aid treatment eg coma position.
• Provision of information on hyperglycaemia including:
Polyuria and polydipsia.
Need for extra toilet privileges and access to water.
• Awareness that infection control protocols must be adhered to during blood glucose
monitoring.
• Provision of a suitable environment for glucose monitoring or insulin injections if
required during school hours.
• Awareness that some children now use a continuous subcutaneous insulin pump.
• Emergency contact details.
It is useful to have a photo of the child with important contact numbers in the staff room and
in each classroom to alert all staff including relief and part time staff. A medical alert
information card should be kept in the child’s records. The child should wear a medical
identification bracelet or necklace at all times.
Issues to be Considered in the Individual Care Plan
Parents/care-givers should meet with the relevant school personnel as soon as practicable to
discuss the issues involved in the care of their child at school. An individual care plan should
be developed and reviewed regularly. In general, the younger the child, the greater is the
supervision required at school. The extent of the individual care plan will vary greatly and
Chapter 19: School
198
will be influenced by the consideration of the following issues by the school and the
parents/care-givers:
• Child’s level of understanding and knowledge of diabetes.
• Child’s developmental stage and ability to accept responsibility.
• Current treatment recommendations for the individual child.
• Any additional medical problems (eg coeliac disease).
• Child’s usual hypoglycaemic symptoms.
• Avoiding delays in meals, snacks.
• Treating hypoglycaemia immediately.
• Providing the school with an emergency supply of rapidly absorbed carbohydrate (eg
jellybeans) in the classroom or wherever the school activity is undertaken.
• Providing extra snacks before, during and possibly following exercise.
• Knowing which foods are easily accessible and easy to consume (eg fruit that does not
require peeling).
• Not leaving a child unaccompanied during or after a hypoglycaemic episode (eg in sick
bay).
• Knowing that the child should not be sent away unaccompanied by an adult from the
classroom to test his/her blood glucose during a suspected hypoglycaemic episode.
• Informing parents/care-givers of the time and nature of the hypoglycaemia (a
communication book noting unusual occurrences is helpful for teachers and parents).
• Encouraging the child to eat all of his/her meal (mealtime supervision may be necessary
for primary school children. Parents need to be informed if meals are not eaten).
• Being aware that birthday parties at preschool and primary school should not exclude
the child with diabetes, as this is a ‘special treat’ occasion and should be so for all the
children. Any special considerations (eg provision of diet drinks) should be discussed
with the child’s parents or caregivers.
• Providing access to the canteen, recognising that this may need some restrictions.
• Encouraging the child to report hypoglycaemia to school personnel. Teachers need to
be cognisant of the child’s personality and feelings, and encourage communication.
• Knowing that following a hypoglycaemic episode children usually recover sufficiently
to rejoin the class, although cognitive function may be impaired for several hours.5;6
However, if the episode occurred during a sports activity, the child should rest for 10 15 minutes before recommencing the activity.
• Helping to fit diabetes into the school routine to prevent the child from feeling different
(eg they should eat at the same time as the other children, be given privacy to give
injections or do blood tests).
• Determining exactly the physical location where in the school glucose testing and
insulin injections will take place.
• Assisting and encouraging the child gradually to take on some responsibility for the
diabetes tasks eg negotiating how much reminding the child would like in order to
remember to eat on time and how much he/she would like to be left alone.
• Allowing extra access to toilets and drinks when blood glucose levels are high.
• Notifying parents in advance of special events, eg excursions, swimming carnivals,
changes to meal times.
• Knowing the impact which diabetes may have on the functioning of the child and
family (awareness and acknowledgment of parental concerns inspires confidence,
reduces anxiety and their tendency to be over-protective).
• Knowing how blood glucose levels can affect concentration and behaviour.
• Knowing that diabetes should not alter the child’s academic potential.
Chapter 19: School
199
•
Encouraging full participation in all school social, sporting and academic activities,
including excursions and camps.
Detentions
Teachers should be aware of the need for regular carbohydrate intake and that eating may be
necessary during detention to avoid hypoglycaemia.
Travel to and from School by Bus
Students with type 1 diabetes should be allowed to eat on the bus to avoid hypoglycaemia. A
‘bus’ card approved by transport authorities is available for such special provision in some
States.
Emergencies at School
If severe hypoglycaemia causes a child to have a seizure, be unconscious or so disorientated
that oral treatment is not possible or is dangerous, the school personnel should lay the child in
the coma position and call an ambulance, stating that it is a diabetic emergency (dial 000).
School Examinations
If an examination coincides with the child’s or adolescent’s usual meal or snack time, it is
advisable for the child to nibble small amounts of bite-sized carbohydrate food, eg nuts and
raisins, throughout, rather than risk having hypoglycaemia by waiting to eat until after the
examination. Examination candidates need to be aware that their food should not be wrapped
in ‘noisy’ packaging.
High School Examinations
The school is required to send an ‘Application for Candidates with Disabilities’ form,
accompanied by a medical certificate, to the ‘Special Provisions for Students’ programmes
provided by the individual State or Territory authorities responsible for senior examinations
some months prior to the examination. Parents in each State or Territory should enquire about
the procedures available to children and adolescents who may experience difficulties with
their diabetes during examinations from their diabetes centres, schools or Diabetes Australia.
Most States allow the student to:
• Take in bite-sized starchy food.
• Have easy access to leave the room as necessary.
• Take in a glucose meter and test strips.
• Have extra time to do an initial blood glucose test, to correct a blood glucose reading
under 5 mmol/L and to re-test it.
The provisions may be made on an individual basis depending on the recommendations of the
medical practitioner. It is advised that the student receives a copy of the provisions made for
him or her. It should be noted that students experiencing hypoglycaemia during the Higher
School Certificate examinations (or equivalent in other States) should apply to be treated as
an ‘illness/misadventure case’. Giving extra time to compensate for the occurrence of a
hypoglycaemic episode may not compensate accurately for the time lost nor allow for the
Chapter 19: School
200
effect of hypoglycaemia on the child’s concentration Students treated as an
illness/misadventure case usually receive a mark based on a school assessment in place of
their actual examination mark.
School Camps
Students with diabetes can participate fully in school camp programs. Usually students attend
camps when they are reliably independent in the care of their diabetes. This includes the
ability to:7
• Inject.
• Do blood glucose tests.
• Recognise/treat hypos.
• Understand the importance of timed meals.
• Understand a food plan, dietary carbohydrate portions or serves and the need for extra
food before, during and after physical activity.
Parents/guardians should meet with the organisers before the camping event.7
Each camper should have a standardised medical information sheet completed prior to the
camp.8
All members of staff must be aware of the child with diabetes. The student’s friends and
room mates should also be aware.
Staff must know about:7
• Food planning and the need for carbohydrate with all meals and snacks.
• Blood glucose testing.
• Prevention of hypos.
• Recognition and treatment of hypos.
• Sick-days.
• When to call for medical help and how to arrange medical evacuation.
The extra exercise at camps increases the risk of hypos. The insulin dose may need to be
reduced by up to _ of the usual insulin dose.
Carbohydrate should be served regularly with every meal and snack. Additional
carbohydrate should be available for prevention and treatment of hypos.
Short-term Effects of Fluctuations in Glycaemia on Cognitive Function
In a case series of 47 children with type 1 diabetes cognitive function was found to remain
impaired for a variable period of time following a mild hypoglycaemic episode (despite
complete resolution of the hypoglycaemic symptoms) therefore confirming that there is a
time lag between recovery rate of physical symptoms and cognitive function in children
following a mild hypoglycaemic episode.5 Decreased cognitive function was also found
during hyperglycaemia in an RCT in 8 out of 12 subjects.9 Mood disturbances have been
documented the day after nocturnal hypoglycaemia.10
Long-term Effects of Fluctuations in Glycaemia on Cognitive Function
Studies have shown that cognitive function is decreased among some children with early
onset (<7yrs)11;12 and longer duration (>5yrs duration)11;13 of diabetes.
Chapter 19: School
201
Children who had experienced hypoglycaemic seizures were significantly more likely to
have a decline in verbal IQ score and other cognitive aspects of perception, fine motor,
visuomotor, visual memory and attention.12;14;15
Two longitudinal studies found that the expected cognitive developmental gains
(especially verbal skills) were smaller than expected when children were followed from
diagnosis of type 1 diabetes to one year,16 two years17 and 6 years post diagnosis.18
A prospective study in Switzerland found cognitive impairment was associated with male
gender, young age at diagnosis (before age 6 years), more severe metabolic disturbance at
diagnosis and chronic poor metabolic control.19
The Evidence
The evidence for the effect of type 1 diabetes on cognitive function in children and
adolescents with type 1 diabetes is listed in Evidence Table 19.1.
• A case series showed that cognitive function remained impaired for a variable period of
time following a mild hypoglycaemic episode despite complete resolution of the
hypoglycaemic symptoms.5(IV)
10
• Mood disturbances have been documented the day after nocturnal hypoglycaemia. (III-2)
• In an RCT decreased cognitive function was found during hyperglycaemia in 8 out of 12
subjects.9(II)
• Studies have shown that cognitive function is decreased in some children who have a
history of hypoglycaemic seizures.12;14;15(IV)
• Early age of onset, longer duration of diabetes and prolonged hyperglycaemia and poor
metabolic control are also associated with a higher risk of cognitive dysfunction.11-13;19(IV)
• Two longitudinal studies found that the expected cognitive developmental gains
(especially verbal skills) were smaller than expected when children were followed one to
six years from diagnosis of type 1 diabetes.16;17;18 (IV)
• Parents/care-givers and teachers should be aware that discrimination or stigmatisation is
unacceptable.20(C)
• Parents/care-givers and teachers should be aware that diabetes should not be the cause
non-participation in any school activity.20;21(C)
• Parents/care-givers should meet with the relevant school personnel as soon as practicable
to discuss the issues involved in the care of their child at school.20(C)
4
• An individual care plan should be developed and reviewed regularly. (C)
• Parents/care-givers and teachers should be aware how to recognise and treat
hypoglycaemia.20;21(C)
• An emergency supply of rapidly absorbed carbohydrate should be readily available in the
classroom or wherever the school activity is undertaken.20;21(C)
• During or following hypoglycaemia or suspected hypoglycaemia, a child must not be
expected to walk to a ‘medical room’ nor left unaccompanied.20;21(C)
• Parents/care-givers and teachers should be aware that cognitive function and mood may be
affected for some hours after hypoglycaemia.5;10 (III-2, IV)
• Parents/care-givers and teachers should be aware that decreased cognitive function may
occur when hyperglycaemia is present.9(II)
Chapter 19: School
202
•
Parents/care-givers and teachers should be aware that risk factors for cognitive
dysfunction include a history of hypoglycaemic seizures,12;14;15 early age of onset and
longer duration of diabetes.11-13;16;17;18(IV)
• Parents/care-givers, teachers and students should be aware that students with diabetes
sitting for the higher examinations may apply for special provisions.21(C)
II = Evidence obtained from at least one properly designed RCT
IV = Evidence obtained from case series, either post-test or pre-test and post test
Reference List
1.
2.
3.
4.
5.
6.
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21.
Canadian Diabetes Association: Standards of care for students with type 1 diabetes in school. Canadian Journal of Diabetes Care
23:66-70, 1999
Gallant RD: School achievement and absence in children with chronic health conditions. Journal of Pediatrics 106:683-687, 1985
Ryan C, Longstreet C, Morrow L: The effects of diabetes mellitus on the school attendance and school achievement of adolescents.
Child: Care, Health & Development 11:229-240, 1985
American Diabetes Association: Care of children with diabetes in the school and day care setting. American Diabetes Association.
Diabetes Care 26:131-135, 2003
Puczynski MS, Puczynski SS, Reich J, Kaspar JC, Emanuele MA: Mental efficiency and hypoglycemia. Journal of Developmental
& Behavioral Pediatrics 11:170-174, 1990
Strachan MWJ, Deary IJ, Ewing FME, Frier BM: Recovery of cognitive function and mood after severe hypoglycemia in adults
with insulin-treated diabetes. Diabetes Care 23:305-312, 2000
Silink M, Mellor L, Mc Gill M, Middlehurst A, Jackson L, Phelan H, and Harris G. Diabetes information - Camps. 2003.
Ref Type: Pamphlet
Davis EA, Soong SA, Byrne GC, Jones TW: Acute hyperglycaemia impairs cognitive function in children with IDDM. Journal of
Pediatric Endocrinology & Metabolism 9:455-461, 1996
study. Journal of Pediatrics 134:503-506, 1999
Rovet JF, Ehrlich RM, Czuchta D: Intellectual characteristics of diabetic children at diagnosis and one year later. Journal of
Pediatric Psychology 15:775-788, 1990
children 2 years after disease onset. Diabetes Care 21:379-384, 1998
Schoenle EJ, Schoenle D, Molinari L, Largo RH: Impaired intellectual development in children with Type I diabetes: association
with HbA(1c), age at diagnosis and sex. Diabetologia 45:108-114, 2002
International Society for Pediatric and Adolescent Diabetes: Consensus Guidelines for the Management of Type 1 Diabetes Mellitus
in Children and Adolescents. Zeist, Netherlands, Medforum, 2000
Chapter 19: School
203
Diabetes camps are an integral component of overall care and support for diabetic children
and adolescents in Australia. Diabetes camps are held annually in most states in a variety of
settings. Despite the varying nature of different diabetes camps all have several features in
common. These are:
• Camps are primarily recreational and enjoyable.
• Camps provide both overt and subliminal peer support.
• Camps provide a safe environment for children and adolescents to pursue more
challenging activities (physical or social) than they would previously have undertaken.
• Camps provide education and assistance in managing type 1 diabetes.
Background
Diabetes camps have been a part of diabetes care for almost as long as insulin therapy has
been available. The first diabetes camp was held in Detroit in the US in 1925.1 In Australia
diabetes camps have been held since 1947.2 Participation in diabetes camps is now
recognised as an important aspect of care for children and adolescents with diabetes.3
Guidelines and standards for diabetes camps have been published for most countries
including Australia.4;5
The Need for Diabetes Camps in Australia
Australian and international research has shown that many children and adolescents with
diabetes have needs that are inadequately met in the context of traditional clinical encounters
with either a medical practitioner or diabetes nurse specialist. These needs include:
• Poor quality of life and functional health (particularly in children and adolescents from
regional Australia).6;7
8;9
• High rates of depression, anxiety, behavioural, cognitive and mood disorders.
10
• Feeling isolated.
11
• Feeling disempowered and helpless.
12
• Lacking meaningful age-specific diabetes information.
7
• Significant negative impact on family function.
Meeting these needs is important both in terms of overall outcomes for individuals and also
for the associated potential benefits with regard to specific clinical outcomes. Deteriorating
metabolic control through adolescence is well documented in young people with diabetes13
despite the application of substantial health-care resources.14 Peer-based and role model
support, fundamental aspects of diabetes camps, have the potential to improve outcomes in
these areas.15
Benefits
Diabetes camps provide an environment where having diabetes is the ‘norm’ rather than
something that sets children and adolescents apart from their peers. Given that camps are
organised around diabetic routines (meal-times, injection times, finger-prick testing times etc)
many campers report that being on camp is ‘…like having a holiday from their diabetes’, in
that they don’t have to worry about routine- ‘…it just happens’. In most camps not only the
campers but also the leaders have diabetes, thus providing a mini-society where both the
members (campers) and elders (leaders) all have one common bond. This creates an
204
environment where there is both peer support and aspirational motivation. Camps often
provide the impetus for establishing ongoing social groups, pen pals, internet chat-room
groups etc that can provide ongoing, year-round support. Camp staff who also have diabetes
can be valuable mentors and role models to the camp participants.
Goals
The goals of diabetes camps are:
• To be enjoyable.
• To allow campers to compare experiences with each other and feel less isolated.
• To increase the confidence of campers in both social and physical activities.
• To allow campers to feel less depressed and anxious, and more positive about their
future lives.
• To allow campers to feel less depressed and anxious, and more positive about their
future lives.
• To allow campers to gain perspective on their own family dynamics.
• To motivate campers to undertake aspects of their own diabetes care (such as selfinjecting and finger prick testing) when there has been child or parental resistance
preventing this from occurring.
• Improve diabetes-related knowledge of campers.
In short, diabetes camps are about individual empowerment through increased confidence,
understanding and motivation.
Other Benefits
Diabetes camps also have other non-camper benefits. These include:
• Parental respite.
• Establishment of ongoing peer-support networks.
• Useful postgraduate, reality-based education for training diabetes health care
professionals (medical staff, nurse educators dietitians etc).
Prerequisites
Above all else diabetes camps must provide a safe environment for both campers and camp
staff. This entails subscribing to an agreed set of standards and protocols prior to the
establishment of camps. Standards and protocols should specify leader to camper ratios,
levels of medical and paramedical support, dietary routines, injection routines, hierarchy and
responsibility of camp organisers, leader and camper application processes, emergency and
evacuation protocols and indemnity arrangements. Many of these issues are broadly covered
in the Diabetes Australia camping standards.4 However, some issues are regional and need to
be specifically organised for individual camps. Diabetes camps require a high level of support
from both medical and paramedical staff in order to provide an adequate level of health safety
for campers. Camp leaders, however, are the key component to successful diabetes camps.
Camp leaders should:
• Be suitable role models for young people with diabetes.
• Be mature, enthusiastic and positive in their interaction with campers.
• Have a basic knowledge of diabetes.
• Have knowledge of hypoglycaemia prevention, recognition and treatment.
205
•
Know how to use, maintain and adjust the insulin dose as well as doses of pumps (if
campers using an insulin pump are attending).
• Have the ability to arrange prompt medical aid when appropriate.
• Have a knowledge of appropriate age-related sports and activities for children and
adolescents with diabetes.
• Have a solid grasp of risk-minimisation principles and how these apply to supervision
of the various camping activities.
Medical Management
A written plan including camp policies and medical management procedures should be
available at camp.5 A standardised medical information form should be completed for each
camper (by his/her family and the managing physician) prior to attending diabetes camp.
Multiple blood glucose determinations should be made throughout each 24-hour period.
These should be done before meals and at bedtime. Extra test should be done (throughout the
day and also overnight if required) following prolonged strenuous activity, prior
hypoglycaemia, after extra insulin doses, or if the child has symptoms of
hypo/hyperglycaemia or other physical complaints. All blood glucose levels and insulin
dosages should be recorded in a format that allows for review and insulin dose alteration if
required.
Due to increased physical activity it may be necessary to decrease the home insulin dosage
by 10-30% (occasionally more), especially in those children with good control who were not
active before the camp. Three meals and three snacks should be given at set times each day.
Additional food should be available for the treatment of hypoglycaemia at all times.
Universal precautions for procedures involving blood draws should be followed.
Appropriate containers for disposal of sharps should be available.
Conclusion
Diabetes camps are a valuable aspect of care for children and adolescents with diabetes. They
are highly popular with both campers and leaders (as is evidenced by high camper and leader
return rates). Whilst diabetic peer group interventions have been shown to be more effective
than traditional clinical encounters in improving outcomes for adolescents,16 it is difficult to
quantify the clinical and psychological benefits of camping per se for young people with
diabetes. The anecdotal experience from diabetes health care professionals however is highly
positive.17;18 The recent adoption of Australian national standards for diabetes camps should
further improve the safety and quality of the diabetes camping experience.
Information on diabetes camps
Further information regarding diabetes camps may be obtained from Diabetes Australia and
major diabetes education centres.
The Evidence
No studies were identified specifically demonstrating the benefits of diabetes camps on
glycaemic control for children and adolescents with type 1 diabetes.
206
• Diabetes camps should be an integral component of overall care and support for diabetic
children and adolescents in Australia.19;20(C)
3
• Diabetes camps must provide a safe environment for both campers and camp staff. (C)
• Camps should be organised using an agreed set of standards and protocols. Standards and
protocols should specify leader to camper ratios, levels of medical and paramedical
support, dietary routines, injection routines, hierarchy and responsibility of camp
organisers, leader and camper application processes, emergency and evacuation protocols
and indemnity arrangements.5(C)
• A standardised medical information form should be completed for each camper (by his/her
family and the managing physician) prior to attending diabetes camp.5(C)
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Travis LB, Schreiner B: Camps for children with diabetes: a philosophy and its application. Diabetes Educator13-20, 1984
Court JM: A holiday camp for diabetic children. Medical Journal of Australia 334-337, 1962
Mellitus in Children and Adolescents. Medical Forum International, 2000
Diabetes Australia. Camping Standards: Guidelines for the conduct of educational camps for children and teenagers with diabetes.
2003.
GA: Regional and urban Victorian diabetic youth: clinical and quality-of-life outcomes. Journal of Paediatrics & Child Health
38:593-596, 2002
Wake M, Hesketh K, Cameron FJ: The functional health status of children with diabetes. Diabetic Medicine 17:700-717, 2000
Northam EA, Matthews LK, Anderson PJ, Cameron FJ, and Werther GA. Psychological morbidity and health outcome in type 1
diabetes - perspectives from a prospective longitudinal study (submitted to Diabetic Medicine). 2003.
Hauser ST, Jacobson AM, Lavori P, Wolfsdorf JI, Herskowitz RD, Milley JE, Bliss R, Wertlieb D, Stein J: Adherence among
children and adolescents with insulin-dependent diabetes mellitus over a four-year longitudinal follow-up: II. Immediate and longterm linkages with the family milieu. Journal of Pediatric Psychology 15:527-542, 1990
Kuttner MJ, Delamater AM, Santiago JV: Learned helplessness in diabetic youths. Journal of Pediatric Psychology 15:581-594,
1990
Fox C: The wasted resource: helping young people with diabetes to help each other. Diabetic Medicine 3:475-476, 1986
Dabadghao P, Vidmar S, Cameron FJ: Deteriorating diabetic control through adolescence-do the origins lie in childhood? Diabetic
Medicine 18:889-894, 2001
Cameron FJ, Widdison J, Boyce D, and Gerbert R. Comparison between optimal and actuarial health care costs of adolescents with
diabetes. Journal of Paediatrics and Child Health . 2003.
Olsson C, Toumbourou J, Bowes G, Walsh B: Therapeutic Peer Support. In Diabetes and the Adolescent. 1 ed. Werther GA, Court
JM, Eds. Melbourne, Miranova Publishers, 1998, p. 217-230
Anderson BJ, Wolf FM, Burkhart MT, Cornell RG, Bacon GE: Effects of peer-group intervention on metabolic control of
adolescents with IDDM. Randomized outpatient study. Diabetes Care 12:179-183, 1989
Court JM: Camping for Youth with Diabetes. In Diabetes and the Adolescent. 1 ed. Werther GA, Court JM, Eds. Melbourne,
Miranova Publishers, 271-281, 1998
Rosenbloom AL: Why diabetes camp? Clinical Pediatrics 40:511-516, 2001
207
Families are encouraged not to restrict their travel plans because of diabetes in the family.
However, to make the holiday safe and enjoyable, families do need to consider:
• The length of the journey.
• The possibility of delays.
• The timing between insulin injections and meals.
• The availability of carbohydrate food.
• Access to medical services and diabetes supplies.
• Changes of climate.
• Changes of types of food.
• Changes in activity levels (increases in physical activity may require reduction of
insulin dosage).
• Changes in meal and sleep routines (especially when crossing time zones).
• The management of sickness away from home.
Preparation
The child or adolescent with diabetes should have a medical visit and see the diabetes
educator a minimum of 4-6 weeks prior to departure in order to:1-3
• Arrange necessary immunisations e.g. tetanus booster, malaria prophylaxis.
• Assess glycaemic control and diabetes management.
• Arrange scripts and medications to take (insulin, glucagon, gastrolyte).
• Organise appropriate identity/Medic-Alert bracelet.
• Discuss necessary adjustments to be made to the diabetes regimen for the flight/long
coach trip, and holiday activities with the main aim being avoidance of hypoglycaemia
(consider notifying the airline of the child’s special needs).
• Learn how to use short-acting insulin.
• Prepare an emergency kit for sick day management.
• Discuss management of illness away from home.
• Arrange a card with emergency commands (eg ‘I need sugar quickly’) in the
appropriate language.
• Prepare the following documentation:
Introductory letter for an overseas doctor, ie a summary letter of the child’s medical
history and current treatment outline (check with the consulate of the country to be
visited if they wish to sight these letters prior to departure).
Letter for customs stating the need to carry syringes, insulin and other medical
supplies.
Translated letters in the appropriate language(s).
Travel insurance documents.
Contact telephone, fax numbers and addresses of diabetes services in area to be
visited.
Contact details of the child’s physician or diabetes educator in Australia.
Supplies
Families need to arrange:
• Enough insulin, syringes, pen needles, glucometer, blood and urine test strips for
duration of the anticipated stay plus an extra supply. The insulin, glucagon, glucometer
208
•
•
•
•
•
•
•
need to be protected from extremes of temperature if these are anticipated on the trip
(use wide necked thermos/other insulated container or packing).
Insulin, glucagon and testing equipment to be readily available in hand luggage, and be
divided between two bags to avoid complete loss in case one bag is lost.
Insulin should only be carried in hand luggage and not placed in luggage in the hold.
Readily available food for treating hypoglycaemia.
Enough extra carbohydrate food, the equivalent of two meals, in case of unexpected
delays or unsuitable food being provided by airline or restaurant (insulin should be
given when it is certain that food is about to be served or is readily available). Airlines
tend to give diets for type 2 diabetes if contact is made regarding dietary needs. This is
usually not appropriate for children with type 1 diabetes as there is little carbohydrate
provided. Families should also take food with them when leaving the aircraft as
unexpected delays may occur at any time, even at transit stops or the destination itself.
Readily available bottled drinks and water.
Loperamide for diarrhoeal illnesses. This medication should not be used in the very
young and in general is over-prescribed. If travelling overseas, loperamide may be a
useful stand-by in case of severe diarrhoea.
Antiemetics. These medications are in general not usually used in children but may be
of use if adolescents with diabetes are travelling overseas.
Management of Diabetes on Long Flights
The detailed management of the diabetes during flights that are long and involve many time
zones should be discussed with the diabetes educator or the physician well before the
departure date. The best way of managing the insulin replacement will vary from individual
to individual and will depend on the insulin regimen being used.
Generally, no adjustment is required when travelling north or south. Adjustments may be
necessary if travelling east or west, especially if six or more time zones are being crossed.2
For westward travel the shift in time zone means that the day will be much longer therefore
extra meals will require extra doses of insulin.3;4 For eastward travel the day will be cut short
and the time between injections decreases, therefore requiring a lower insulin dose.3;4
For some, it is easiest to have a watch that remains on the time of the place of origin and to
keep to the routines that would have been given for those times. This is possible providing
the families have their own food supply and do not rely on airline meal times. Following
arrival, adjustments need to be made to the insulin regimen to bring it into line with local
times.
For others, especially if there is a major variance in the morning and evening doses (eg
patients taking twice-daily insulin) an acceptable regimen is to change to using pre-meal
(approximately 6-hourly) injections of short-acting insulin during the flight.5 The need to
have an independent source of food and perform frequent blood glucose monitoring is still
essential.
The Evidence
The evidence on insulin adjustment during travel when crossing time zones is listed in
Evidence Table 21.1.
• There are no paediatric studies addressing the issue of glycaemic control and insulin
adjustment while travelling.
• During westward travel the day will be much longer therefore extra meals will require
extra doses of insulin. A case series of 27 adults with type 1 diabetes found that for
209
westward travel extra insulin was required (3.1% of total daily insulin dose per time shift
hour).4(IV)
• The same study found that less insulin was required during eastward travel (total daily
insulin dose reduced by 2.6% per time shift hour). During eastward travel the day is cut
short and the time between injections decreases therefore requiring a lower insulin
dose.4(IV)
• A case series (which included some children) found that patients were generally satisfied
with a simplified regimen using pre-meal injections of short-acting insulin (approximately
6-hourly) during long haul flights.5(IV)
• The detailed management of diabetes during visits to distant locations or foreign countries
should be discussed with the diabetes educator or the physician well before the departure
date.1;6(C)
• The detailed management of diabetes on long flights crossing many time zones should be
discussed with the diabetes educator or the physician well before the departure date.1;6(C)
• The family should be advised to arrange enough insulin, syringes, pen needles,
glucometer, blood and urine test strips for the duration of the anticipated stay plus an extra
supply.1;6(C)
• The family should be advised to have insulin, glucagon and testing equipment readily
available in hand luggage, and to have essential supplies divided between two bags to
avoid complete loss in case one bag is lost.1;6(C)
• The child or adolescent with diabetes should be advised to have his/her own food supply
and not rely on airline meal times.1;6(C)
• The family should be advised that no major change to the insulin regimen is required for
north-south travel.1(C)
• The family should be advised that extra insulin may be required for westward travel as the
day will be much longer and extra meals will require extra doses of insulin.4(IV)
• The family should be advised that less insulin may be required during eastward travel as
the day is cut short and the time between injections decreases therefore requiring a lower
insulin dose.4(IV)
• Switching to a simplified regimen of pre-meal injections of short-acting insulin during
long haul flights should be considered as an option.5(IV)
Reference List
1.
2.
3.
4.
5.
Ambler G, Barron V, May C, Ambler E, Cameron F: Caring for Diabetes in Children and Adolescents. A parents manual. Sydney,
Dewey CM, Riley WJ: Have diabetes, will travel. How to help patients avoid diabetic emergencies away from home. Postgraduate
Medicine 105:111-126, 1999
Gustaitis J: Taking to the air with diabetes. Diabetes Self-Management 19:36-37, 2002
Sane T, Koivisto VA, Nikkanen P, Pelkonen R: Adjustment of insulin doses of diabetic patients during long distance flights.
Jones H, Platts J, Harvey JN, Child DF: An effective insulin regimen for long distance air travel. Practical Diabetes 11:157-158,
1994
6.
210
The National Center for Complementary and Alternative Medicine at the National Institutes
of Health (USA) defines CAM as ‘a broad domain of healing resources that encompasses all
health systems, modalities, and practices and their accompanying theories and beliefs, other
than those intrinsic to the politically dominant health system of a particular society or culture
in a given historical period’.1;2 It is generally understood to be health care practices that are
outside of those used by conventional medicine; however, there may be some overlap.
There is some evidence to support the use of some complementary and alternative
medicine therapies for particular conditions. However, for the majority of such therapies
there is limited or no information to support their use and there is a lack of information about
their safety.
Like any other medications, complementary and alternative medicine therapies have the
potential for adverse effects and for interactions with conventional treatments or other
complementary and alternative medicine therapies.3
Complementary and alternative medicine may include medicinal (herbal remedies, dietary
supplements, vitamins and minerals, naturopathic and homeopathic remedies), or nonmedicinal remedies (such as chiropractic, osteopathy and naturopathy).
Complementary and Alternative Medicine use in Diabetes
The amount and nature of complementary and alternative medicine used over a twelve-month
period in children attending a diabetes clinic at a tertiary referral hospital in Australia was
estimated to be:4
• 49% (44% medicinal and 16% non-medicinal).
• 18% medicinal, if the use of vitamins and minerals were excluded.
The most commonly used medicinal remedies were multivitamins and minerals, vitamin
C, echinacea, other herbal treatments and homeopathic remedies.
There are many complementary and alternative medicine treatments that have been
recommended for use in diabetes, but there appears to be little consensus between authors
and little evidence to support these recommendations.5
• There are no complementary and alternative medicine therapies that have been shown in
controlled trials to cure diabetes or improve control. It is important to remember that many
complementary and alternative medicine therapies used by children with diabetes may be
for treatment of other conditions or for general health reasons. Children with chronic
illnesses are, in general, more likely to use complementary and alternative medicine.6 A
systematic review of all published prevalence studies (n=10) reporting the use of
complementary and alternative medicine in the paediatric population found that the
reported prevalence varied from 9% to 70%.6(IV)
Ketoacidosis and death have been described when insulin has been omitted as part of an
alternative treatment.7 Parents should be warned that insulin should never be significantly
reduced or omitted as part of an alternative treatment.
Clinicians and Complementary and Alternative Medicine
Clinicians have a responsibility to ensure that they are aware of all the forms of therapies that
patients are using. In addition, it is important to try to understand different approaches to
health and help parents in making informed and safe choices.
211
Studies consistently show that families rarely tell their treating doctors about
complementary and alternative medicine use.8;9 Thus asking about their use should always be
a part of the routine history taking process.
In order to discuss complementary and alternative medicine effectively, it is important for
clinicians to:4;10;11
• Ask about their use. Specific questions about different types of complementary and
alternative medicine may be required; for example:
Naturopathic or natural treatments.
Herbal remedies.
Dietary supplements.
Vitamins and minerals.
Homeopathic treatments.
• Avoid dismissal of complementary and alternative medicine, which may discourage
families from discussing their actual use. Patients may be concerned about a clinician’s
response to their use.
• Be prepared to discuss complementary and alternative medicine use and discuss the
risks and benefits of different therapies.
• Understand the reasons and motivations for the health care choices that families make.
• Be aware of and explain to patients that the quality of advice available on the Internet is
variable and inconsistent. A recent study looking at complementary and alternative
medicine websites for treatment of diabetes found that out of 13 websites, one gave
definitely harmful advice (by actively discouraging conventional diabetes therapy) and
a further five websites were deemed to be potentially harmful.12
Discussing complementary and alternative medicine with families may involve trying to
obtain appropriate information about the particular treatment, and like other treatments
weighing up the potential benefits and risks with the family.
Management of a Patient using Complementary and Alternative Medicine
When a child taking complementary and alternative medicine is admitted to hospital the
following steps should be taken:13
• Consider the possible effects and interactions of the particular substance.
• Phone the local drug or poisons line for information if necessary.
• If the parent wishes for the child to continue taking the remedy whilst in hospital, the
drug should have an AUST R or AUST L number (phone drug information to find out).
AUST R medicines are assessed for safety, quality and effectiveness. They include
all prescription-only medicines and many over-the-counter products such as those
for pain relief, coughs and colds and antiseptic creams.14
AUST L medicines are used for minor health problems and are reviewed for safety
and quality. They include sunscreens over SPF4 and many vitamin, mineral, herbal
and homoeopathic products.14
• If the drug has a valid AUST L or AUST R number, and the admitting consultant
approves the use of that particular complementary and alternative medicine in the
patient, then this should be documented in the patient notes. The parents may then
supply, administer and record the administration of the complementary and alternative
medicine whilst in hospital.
• If the drug does not have an AUST L or AUST R number it should not be administered
in hospital.13 If the parents insist on its use, they should be counselled and advised that
they cannot administer the drug whilst in hospital. If they still choose to use the drug
212
they should sign an ‘Against Medical Advice’ statement and supply, administer and
record any further administration of the complementary and alternative medicine.
Issues to consider when assessing the risks and benefits of complementary and alternative
medicine use include:
• A common misconception that, by being ‘natural’, they are therefore safe. Like all
medical treatments, however, complementary and alternative medicine therapies may
have beneficial effects but may also have side effects.
• The type of therapies being used – medicinal treatments versus non-medicinal
treatments.
• Available information about a particular therapy regarding efficacy, safety and potential
harmful effects.
• The source of the complementary and alternative medicine (eg whether purchased overthe-counter, from a naturopath, etc).
• Where the product was manufactured. Products manufactured and registered with the
Australian regulatory authority, the Therapeutic Goods Administration (TGA), will
have an AUST L or an AUST R number. The ingredients of products without these are
less reliably identified.
• The expectations underpinning their use and the reasons for their use.
Complementary and alternative medicine use is common within the community.
Understanding their use within the context of the family is an important part of clinical care.
The Evidence
We found no studies addressing complementary and alternative medicine therapies in
children or adolescents with diabetes.
• A systematic review of all published prevalence studies (n=10) reporting the use of
complementary and alternative medicine in the paediatric population found that the
reported prevalence varied from 9% to 70%.6(IV)
• Complementary and alternative medicine may include medicinal (herbal remedies, dietary
supplements, vitamins and minerals, naturopathic and homeopathic remedies), or nonmedicinal remedies (such as chiropractic, osteopathy and naturopathy).1(C)
1;6
• Complementary and alternative medicine use is common within the community. (IV)
• In order to improve clinical care health care professionals should aim to understand the use
of complementary and alternative medicine within the family context.10;13(C)
• Families should be advised that no complementary and alternative medicine therapies have
been shown to cure diabetes or improve control.10(C)
• Ketoacidosis and death have been described when insulin has been omitted as part of an
alternative treatment.7 Parents should be warned that insulin should never be significantly
reduced or omitted as part of an alternative treatment.(IV)
• Families should be advised that complementary and alternative medicine therapies have the
potential for adverse effects and for interactions with conventional treatments or other
complementary and alternative medicine therapies.10(C)
• Health care professionals are able to determine the constituents of any complementary or
alternative medicine by enquiries to poisons centres and quoting the medicine’s AUST L or
213
AUST R numbers.14 Drugs without an AUST L or AUST R number should not be
considered for use in hospital.13(C)
IV = Evidence obtained from case series, either post-test or pre-test and post-test.
Reference List
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
National Center for Complementary and Alternative Medicine (NCCAM) and NIH. What Is Complementary and Alternative
Medicine (CAM)? 2003. http://www.nccam.nih.gov/
Panel on Definition and Description, CAM Research Methodology Conference, April 1995.: Defining and describing
complementary and alternative medicine. Alternative Therapies in Health & Medicine 3:49-57, 1997
Drew AK, Myers SP: Safety issues in herbal medicine: implications for the health professions. Medical Journal of Australia
166:538-541, 1997
Cranswick N, Lim A: Complementary and Alternative Medicine: Endocrine consequences. (Abstract). Australian Paediatric
Endocrine Group, Annual Scientific Meeting, Darwin 2002
Ernst E.: Complementary medicine: its hidden risks. Diabetes Care 24:1486-1488, 2001
Ernst E.: Prevalence of complementary/alternative medicine for children: A systematic review. European Journal of Pediatrics
158:7-11, 1999
Gill GV, Redmond S, Garratt F, Paisey R: Diabetes and alternative medicine: Cause for concern. Diabetic Medicine 11:210-213,
1994
Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC: Trends in alternative medicine use in the
United States, 1990-1997: results of a follow-up national survey. Journal of the American Medical Association 280:1569-1575,
1998
Spigelblatt L, Laine-Ammara G, Pless IB, Guyver A: The use of alternative medicine by children. Pediatrics 94:811-814, 1994
Sandler AD, Brazdziunas D, Cooley WC, Gonzalez de Pijem L, Hirsch D, Kastner TA, Kummer ME, Quint RD, Ruppert ES:
Counseling families who choose complementary and alternative medicine for their child with chronic illness or disability.
Pediatrics 107:598-601, 2001
Schmidt K, Ernst E: Complementary/alternative medicine for diabetes. How good is advice offered on websites? Diabetic Medicine
20:248-249, 2003
Department of General Medicine, Royal Children's Hospital, and Melbourne. Use of Complementary and Alternative Medicines for
Inpatients. 2003. http://www.rch.org.au/genmed/CAMguidelines.htm.
Therapeutic Goods Administration. Buying medicines? What's on the Label for me? 2003.
http://www.health.gov.au/tga/docs/html/buymed.htm
214
Resources
The full version of these guidelines are available in pdf format on the NHMRC and
Australasian Paediatric Endocrine Group websites (http://www.racp.edu.au/apeg/).
Diabetes Australia (DA)
Diabetes Australia provides a wide variety of booklets/fact sheets on food and general issues
pertaining to management of type 1 diabetes. The range of services available in each State or
Territory can be obtained by contacting local DA offices. Internet access to the various
Diabetes Australia State and Territory Offices is available through links at
www.diabetesaustralia.com.au
Contact Details for Diabetes Australia States & Territories
DA-NSW
(02) 9552 9912
DA-Victoria
(03) 9667 1777
DA- Queensland
(07) 3846 4600
DA- Northern Territory (08) 8927 8488
DA – Tasmania
(03) 6234 5223
DA- South Australia
(08) 8234 1977
DA – Western Australia (08) 9325 7699
DA – ACT
(02) 6288 9830
Juvenile Diabetes Research Foundation (JDRF)
JDRF provides a variety of brochures on the management of type 1 diabetes in children and
adolescents. Details may be obtained from the JDRF office (1300 363 126), or from the
JDRF website [email protected]
Health Care Card
The Health Care Card is a benefit provided by the Commonwealth Government. It is not
means tested on assets or income criteria. To qualify for the Health Care Card ‘the child,
because of their disability, requires substantially more care and attention than another child of
the same age, without the disability’.
The Health Care Card assists families with the cost of prescriptions under the
Pharmaceutical Benefits Scheme (PBS) and National Diabetes Services Scheme (NDSS) and
with some other concessions. With the Health Care Card the holder can purchase medications
on the prescribed list at a reduced cost.
Applications for the Health Care Card are made through Centrelink. Eligibility for the
Health Care Card is determined on criteria based on the Treating Doctor’s Report (TDR).
Resources
215
Details regarding the Health Care Card may be obtained from any Centrelink office.
Carer Allowance (CA)
The Carer Allowance is an additional benefit to the HCC provided by the Commonwealth
Government. A submission may be made to obtain the Carer Allowance from Centrelink. It
is not means tested on income or assets criteria.
Applications for the Carer Allowance are made through Centrelink. Eligibility for the CA
is determined on criteria based on the Treating Doctor’s Report (TDR).
International Diabetes Federation (IDF) School Information Pack
The IDF School Information Pack provides guidance for teachers and other school staff on
type 1 diabetes in children and adolescents. The pack consists of:
• Medical alert information card.
• Diabetes information for schools.
• Diabetes Information about schools for parents.
• Management of hypoglycaemia poster.
• An information flipchart.
• Emergency card.
• Management plan.
The IDF School Information Pack can be obtained from diabetes centres and Diabetes
Australia. It can also be downloaded form the Diabetes NSW website
http://www.diabetesnsw.com.au/childteens/default.asp?Refid=80
Other Resources
A wide variety of educational resources for health professionals and consumers is available
through large tertiary paediatric diabetes services.
Resources
216
Appendix 1: Guidelines Writing Committee Members and
Contributors
Writing committee members
Professor Martin Silink AM (Chair)
Paediatric Endocrinologist
Institute of Endocrinology and Diabetes
The Children’s Hospital at Westmead
Westmead NSW 2145
Dr Ann Maguire
APEG Fellow (2003)
Westmead NSW 2145
Associate Professor Caroline Clarke
Monash Medical Centre
Clayton VIC 3168
Ms Angela Middlehurst
Diabetes Educator
Diabetes Australia - NSW
Glebe NSW 2037
Associate Professor Jennifer Couper
Dept of Endocrinology and Diabetes
Women’s And Children’s Hospital
North Adelaide SA 5006
Ms Emma Rooney
Assistant Director (Diabetes)
Cancer Control and Diabetes Section
Health Industry and Investment Division
Commonwealth Dept of Health and Ageing
Canberra ACT 2601
Dr Maria Craig
Westmead NSW 2145
Associate Professor Patricia Crock
President APEG (Sep 2003-)
Dept of Paediatric Endocrinology
John Hunter Children’s Hospital
Newcastle NSW 2310
Ms Rebecca Davies
Director, Juvenile Diabetes Research Foundation
St Leonards NSW 2065
Dr Kim Donaghue
President APEG (Sep 2001- Sep 2003)
Westmead NSW 2145
Dr Lillian Jackson
Manager, Diabetes Education Services
Glebe NSW 2037
Dr Karen Luxford
Program Director
National Breast Cancer Centre
Camperdown NSW 1450
Appendix 1: Guidelines Writing Committee Members and Contributors
217
Contributors
Dr Jeremy Allgrove
Department of Pediatrics
Newham General Hospital
United Kingdom
Dr Jan Fairchild
Women’s And Children’s Hospital
North Adelaide SA 5006
Dr Geoffrey Ambler
Westmead NSW 2145
Dr Heather Gilbertson
Dietitian
Royal Children’s Hospital
Parkville VIC 3052
Dr Fergus Cameron
Parkville VIC 3053
Ms Samantha Clarke
Dietitian
Westmead NSW 2145
Dr Andrew Cotterill
Matre Children’s Hospital
South Brisbane QLD 4101
Associate Professor Noel Cranswick
Director, Clinical Pharmacology
Parkville VIC 3052
Associate Professor Chris Daly
Head, Periodontics
Faculty of Dentistry
University of Sydney NSW 2006
Dr Elizabeth Davis
Department of Endocrinology
Princess Margaret Hospital
Perth WA 6001
Ms Gabrielle Donlevy
Dietitian
Northern Paediatric and Adolescent Diabetes
Service (NeePADS)
St Leonards NSW 2065
Dr Anthony Duffin
Podiatrist, Institute of Endocrinology and Diabetes
Westmead NSW 2145
Ms Christie Graham
Dietitian
Parkville VIC 3052
Ms Rachel Hayes
Senior Diabetes Dietitian
Institute of Endocrinology & Diabetes
Westmead NSW 2145
Associate Professor Tim Jones
Perth WA 6001
Dr Bruce King
Dept of Paediatric Endocrinology
Newcastle NSW 2310
Dr Anthony Lafferty
Perth WA 6001
Dr Alissa Lim
Clinical Pharmacology Fellow
Parkville VIC 3052
Ms Melinda Morrison
Diabetes Dietitian
Diabetes Australia-NSW
Glebe NSW 2037
Dr Elizabeth Northam
Co-ordinator, Academic and Research Program,
Department of Psychology
Parkville VIC 3052
218
Ms Carmel Smart
Paediatric Diabetes Dietitian
Newcastle NSW 2310
Dr Peter Swift
Secretary-General
International Society for Pediatric and Adolescent
Diabetes
Children's Hospital, The Leicester Royal Infirmary
United Kingdom
Dr Michael Thomsett
131 Wickham Terrace
Brisbane QLD 4000
Ms Sheri Todd
Research Assistant
Murdoch Children’s Research Institute
Parkville VIC 3052
Ms Joanne Turner
Exercise Physiologist/Dietitian
Glebe NSW 2037
Dr Charles Verge
The Sydney Children’s Hospital
Randwick NSW 2031
Professor George Werther
Parkville VIC 3052
Ms Emma White
Diabetes Educator
Diabetes Centre
Monash Medical Centre
Clayton VIC 3168
Associate Professor Richard Widmer
Dept of Dentistry
Westmead NSW 2145
6
8
16
Karvonen
2000
Craig 2000
Verge
1994
Children aged 0-14 years
in New South Wales,
Australia (1990-1991)
Children aged 0-14 years
resident in New South
Wales, Australia over the
period 1992-1996
WHO DiaMond Project
(Multinational Project for
Childhood Diabetes).
Incidence of T1D from
1990 to 1994 determined in
children 14 yrs old from
100 centers in 50 countries
Population
Children aged 0-14 yrs
with T1D
N/A
Outcome
Patients newly diagnosed with T1D by
physicians and diabetes educators.
T1D incidence
T1D incidence
N/A
N/A
T1D incidence
Intervention
N/A
Appendix 2: Evidence Tables
Ref No
5
Prevalence/incidence of type 1 diabetes in children in Australia/worldwide.
Study
Internation
al Diabetes
Federation
(IDF) Atlas
1. 1
Age-standardized incidence rate
of T1D was 14.5 per 100,000
person-yrs
Peak incidence at age 11 (girls),
and 13 (boys)
Seasonal variation (more cases
occur in late autumn/winter)
Results
Australia incidence rate 17.8 per
100,000.
New Zealand incidence rate 15.2
per 100,000.
Fiji incidence rate 0.1 per
100,000.
Finland incidence rate 37.4 per
100,000.
T1D incidence varied from
0.1/100,000 per year in China and
Venezuela to 36.8/100,000 per
year in Sardinia and 36.5/100,000
per year in Finland.
In most populations, the incidence
increased with age and was the
highest among children 10-14
years of age
Incidence of T1D from 1990-1996
was 17.8 per 100,000. There was a
statistically significant rise in
incidence of T1D over this period
(p=0.0003)
Primary ascertainment using a
prospective incidence register
established in 1990. Secondary
source of ascertainment from
National Diabetes Supply
Scheme (government
subsidised scheme for diabetic
supplies)
Capture-recapture method,
ascertainment estimated to be
99% complete
Australian NSW data
Prospective register, with two
independent sources of case
ascertainment. The primary
source was reporting of newly
diagnosed patients by
physicians and diabetes
educators. The secondary
source was National Diabetes
Supply Scheme
Australian NSW data
Well-defined population based
registry; Capture-recapture
method used
Comments
Medline and Pubmed were
searched from 1980 -2003
IV
IV
Well designed
representative
cohort study
Well designed
representative
cohort study
IV
Level
IV
Well designed
representative
cohort study
Design
Systematic
review of all
relevant
population
based studies
219
children
Multicentre international
study
Adults and
included
Of 372 with 5 year risk of
>50% of developing T1D,
339 were randomised.
(169 to the intervention
and 170 to the observation
arm)
84,228 screened
Population
Relative of patients with
T1D
Intervention
close
observation or
low dose s.c.
ultralente
insulin twice
daily
(0.25
u/kg/day), plus
annual 4 day IV
insulin infusion
treatment.
Outcome
Development of diabetes. Median
follow up 3.7 years
Ref No
4
Intervention trials to delay or prevent the onset of type 1 diabetes.
Study
DPT
(Diabetes
Prevention
Trial)
2002
2.1
In people at high risk for
diabetes, insulin in the dose
described here does not
prevent or delay T1D.
The annualised rate of
progression to diabetes was
15.1% in the intervention
group and 14.6% in the
observation group (relative
risk 0.96, 95% CI 0.69-1.34,
p=0.80).
Results
Diabetes diagnosed in 69 in
the intervention group and 70
in the observation group. The
majority were asymptomatic
(102/139, 73.4%).
Data analysed according to
intention-to-treat principle, and
C o m p l i a n c e : Annual noncompliance rate in intervention
group was 5.5%, and 1% in
control group
Losses to follow-up: annual rate
of loss to follow-up was 1.3%
Blinding:
No blinding of participants and
investigators; control group did
not receive placebo because
intervention involved injections
or infusions and some
participants were children
Comments
Randomisation:
Participants allocated to
intervention or control groups
by a centralised computer
system, and were stratified by
baseline glucose tolerance ands
clinical centre
RCT
Design
Level
II
Technical Reports/Consensus Statements
World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO Consultation. Part 1:Diagnosis and Classification. WHO/NCD/NCS/99.2.
1999. Geneva, World Health Organization. Ref Type: Report
American Diabetes Association: Type 2 Diabetes in Children and Adolescents. Pediatrics 105:671-680, 2000
American Diabetes Association: Screening for Type 2 Diabetes. Diabetes Care 26:21-24, 2003
World Health Organization. Screening for Type 2 Diabetes. Report of a World Health Organization and International Diabetes Federation meeting. WHO/NMH/MNC/03.1. 2003. Geneva, World Health
Organization. Ref Type: Report
International Society for Pediatric and Adolescent Diabetes: ISPAD Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Zeist, Netherlands, Medforum, 2000
Technical Reports and Consensus Statements used to formulate the recommendations and principles of clinical practice.
57
28
31
32
Ref No
1
1. 2
Capture-recapture method,
ascertainment was estimated to
be 99.4% complete
220
Multicentre international
study in Europe and
America
Adults and children
included (3 to 40 years)
552 fulfilled criteria of
having confirmed islet cell
antibody levels >20 JDFU
>30,000 first degree
relatives of T1D patients
screened
552 randomised
to receive either
nicotinamide
(1.2gm/m2) or
placebo.
Development of T1D
Concluded that nicotinamide
(in the dose described) does
not delay or prevent the onset
of diabetes in high risk
individuals.
No sig. diff. between
nicotinamide and placebo in
development of T1D. Of 159
participants who developed
diabetes within 5 years, 82
(30%) were on nicotinamide
and 77 (28%) were on
placebo
Study abandoned at interim
analysis after 5 years.
Analysis by intention-to-treat
Losses to follow-up:
1 from each group withdrew
consent after randomisation
549/552 participants began
their trial medication;
Primary variable (diabetes
status) obtained for 447/549
(87%) of patients;
Placebo group: 48 discontinued
treatment, 35 lost to follow-up
Treatment
group:
47
discontinued treatment, 38 lost
to follow-up
Blinding:
All study personnel blinded to
participants’
treatment
allocation;
emergency
unblinding done for 4
participants
8
Ref No
2.2
ENDIT
2004
Study abandoned by NIH at
interim analysis.
Pseudorandomisation:
(computer generated codes
allocated sequentially by
national coordinator)
monitored by an independent
data and safety monitoring
board, with predefined stopping
rules
Quasi-RCT
III-1
221
6
Srinivasan
2004
Introduction of new day care
programme (DDCP) for
newly diagnosed T1D.
Number of participants
ranged from 20 to 223 with
a total of 237 participants in
the outpatient/home care
group. The mean age of
most groups was between
10-13 years. 4 studies were
carried out in USA and
Canada, 1 in Finland, 1 in
Israel
Population
Children with newly
diagnosed type 1 diabetes
The pre-DDCP
cohort comprised
all children
newly diagnosed
with type 1
diabetes from
March 2000 to
November 2000
(n = 49). The
post-DDCP
cohort were those
diagnosed from
November 2000
to August 2001
(n = 61).
Intervention
6 comparative
studies of initial
hospitalisation
compared with
home based or
outpatient mx.
(Siminerio 99
Dougherty 98
Simell 95
Chase 92
Galatzer 82
Spaulding 76)
No sig. diff.
No sig. diff
Decreased from 5.14 days
to 1.70 days (range, 0-10)
No sig. diff. between the
two cohorts in insulin
requirement at 12 months
(pre-DDCP: 0.9 U/kg [95%
CI, 0.8-1.0]; post-DDCP:
0.8 U/kg [95% CI, 0.7-0.9];
P = 0.22),
No sig. diff. in HbA(1c)
level at 12 months (preDDCP: 8.4% [95% CI,
8.0%-8.9%]; post-DDCP:
8.2% [95% CI, 7.9%8.5%]; P = 0.37)
No sig. diff. in adverse
events over the first year
after diagnosis. Both
Others: no. of hosp. contacts,
psychosocial effect on child and
parents, other adverse events, cost
Hospital stay
Insulin requirement
HbA(1c)
Adverse events
No sig. diff.
Admissions to hospital in first 2
years
Acute complications
Results
No sig. diff.
Outcome
Metabolic control
Ref No
5
Benefits of ambulatory care versus hospital in-patient care of patient with newly diagnosed type 1 diabetes
Study
Clar 2003
(Cochrane
Systematic
Review)
3.1
Australian (Sydney) study relevant to
Australian healthcare system
Overall there was insufficient high quality
data.
Outcomes suggest that outpatient
management does not lead to any
advantage in terms of metabolic control,
acute complications, hospitalisations,
psychosocial, behavioural or costs
Ambulatory stabilisation of children with
type 1 diabetes provides similar metabolic
outcomes for the child, and comparable
levels of diabetes knowledge and similar
psychosocial outcomes for the family, to
inpatient stabilisation programs.
5 out of 6 were regarded as low quality
studies.
2 studies were RCT’s, 3 were retrospective
cohort studies and 1 was a prospective
cohort study.
Comments
Rigorous search strategy with appropriate
inclusion criteria
Comparative
study with
historical
controls
Design
Systematic
Review
(Cochrane)
III-3
Level
I
American Diabetes Association: Prevention of Type 1 Diabetes Mellitus. Diabetes Care 26:140, 2003
24
7
23
222
8
9
Kirk 2003
Lee 1992
New diagnosis T1D <18 yrs,
presenting to Texas
children’s hospital,
approximately 30-50 cases
per year
36 newly
diagnosed
children with type
1 diabetes
Ages 0-19
1994-April 2002
UK
An increased risk for poor
glycemic control was
recorded in children living
in one-parent families (p =
0.03) or in families where
the father had a low level of
education (p = 0.04).
Younger age (p = 0.05), a
single-parent family (p =
0.05) and poor glycemic
control (p = 0.02) were
associated with more days of
rehospitalization.
36 newly
diagnosed
children with type 1
diabetes
Ages 3-15
April 1986 –
January 1989
Sweden
Early
discharge to
hospital family
apartment (n =
19)
vs.
Conventional
hospital care
n = 19)
The control
group was treated
initially in a
hospital ward,
while the study
group received
problem-based
learning and
familytherapeutic and
social support in
an out-hospital
training
apartment.
Retrospective
Survey of initial
management
over 8 years
following
specialist nurse
appointment in
1994
Pre 1988 group
were all
hospitalized at
diagnosis. Post
1988 an
outpatient
focused approach
used when
possible.
Fewer admissions at
diagnosis and fewer
episodes of readmission in
outpatient treated group
post 1988
Admission rate
Cost
From April 1995 onwards
mean of 2.0 days, change
from 1994 when
average of 6.3 days
Mean number of days newly
diagnosed patients were
admitted
This institution reported
$100,000 saving per year
36 patients were readmitted
for diabetes related
problems. All of these
patients were treated as
inpatients at diagnosis.
5/36 (14%)
Hospital readmission days:
Study group median 1.0
days; control group 2.0
(p=0.83); no significant
difference
Number able to be fully home
managed from diagnosis
Glycaemic control HbA1c
Hospital readmission
7
Forsander
2000
groups reported similar
scores for the parental
questionnaires
Glycaemic control:
At 2 years after diagnosis,
study group mean HbA1c
6.2 [0.9] versus 6.0 [0.9] in
control group (p=0.46); no
significant difference
At 5 years, study group
mean 7.3 [1.3] versus 7.1
[1.3] in control group
(p=0.58); no significant
difference
American healthcare system therefore cost
data may not be relevant to Australian
health care system.
A very small study in City Hospital
Birmingham UK. Authors make comment
that their figures are not as good as those
from the Birmingham Children’s Hospital
and relate this to social disadvantage (60%
of Asian descent).
Unknown number of days each group
spent in hospital.
2 children lost to follow-up because they
moved to another region
Randomisation:
Method of randomisation not reported.
Retrospective
case series
notes review
Non
comparative
cohort
study
RCT
III-3
IV
II
223
1979 - 1988
UK
New T1D (age 11months –
16 years) managed as
outpatients between 1974
and 182. N=52
49 were managed as
outpatients and 3 admitted
for 18-40 hours due to
diabetic ketoacidosis
236 newly
diagnosed
children with type
1 diabetes
Ages 10-14
Home base
care
vs.
hospital based
care
No parents indicated that
they would have preferred
admission
138/236 received
supervised home
management
Duration of admission in
1979 –1980 was 7 days and
in 1987 –1988, 3 days.
22% of home management
patients vs. 41% of
inpatient managed patients
p=0.004
Glycated Hb was 10.2% in
home treated group and
10.0% in the hospitalised
group. No significant
difference (p=0.37)
Parental satisfaction as judged by
informal feed-back
Proportion of children managed
without hospital admission
Mean duration of hospital stay
Comparison of readmission rates
Concentration of glycated
Haemoglobin
Adverse events
Clinical audit and not a controlled study.
Possible bias as children admitted at
diagnosis is likely to been different from
those not admitted.
American study.
32
Cameron
2002
Case attainment based on
Diabetes Register was 67%
of children in NSW and
ACT.
47 children with T1D <18
years of age from three
regional Victorian
communities (Horsham,
Warrnambool, Sale) were
Population
Audit of 1,190 children with
T1D aged <15years.
Compared
urban with rural
children.
Intervention
Compared
urban with rural
children.
HbA1c
HbA1c
Ref No
31
Study
Handelsman
2001
Outcome
Median yearly
HbA1C for patients
were not obviously
different between
the regional and
Results
Median HbA1c was
8.2% (interquartile
range 7.6-9.1%)
Median HbA1c was
8.2% in both urban
and rural group.
Comments
Confirmed homogeneity of metabolic
control in NSW and ACT regardless of
location, socioeconomic status or system of
care. Social disadvantage was assessed
using a graded post code-based social
disadvantage risk score.
Australian study.
Homogeneity of metabolic control in
Victoria, Australia
Historical
comparison
Retrospective
case series
Comparative
Design
Multicentre, population-based,
cross-sectional study
Differences in glycaemic control between urban and rural children and adolescents with type 1 diabetes in the Australian health care system
12
Swift 1993
3.2
10
Schneider
1983
with outpatient approach
(now including savings due
to decreased readmission
rate)
None reported
IV
Level
IV
III-3
IV
224
urban centres
(HbA1c 8.1% at
urban centre, 8.9%,
8.4% and 8.6% at
the 3 rural centres).
Numbers too small
for statistical
analysis
Literature
reviewed until
June 1999
Compared behavioural
intervention (education or skills
training) with control group.
Emotional/psychological
interventions (18%)
Dietary interventions (19%)
Skills training (39% studies)
Age range 9-21
years.
Most studies from
USA (67.7%)
Intervention
Question asked “Do
educational and psychosocial
interventions for adolescents
with type 1 diabetes have
beneficial effects on biological
and psychosocial outcomes?”
Population
Systematic review
of 62 studies from
Health
Technology
Assessment
Program UK.
Ref No
28
Metabolic measures
Psychosocial
Self or parent reports of
changes in psychological
or interpersonal constructs
(e.g. self-efficacy;
diabetes-specific stress)
Outcome
These studies demonstrate the
variety of intervention and
outcomes that have been
studied. All the pre-, post
design studies reported some
benefit - however because of
the low level of study design
and small numbers these
benefits should be treated as
provisional until more rigorous
results are available
Mean of 12 pooled effect sizes
was 0.33 (95% CI 0.04 – 0.70)
for glycated haemoglobin with
outliers; significant
heterogeneity (0.08 without 2
outliers)
for psychosocial outcomes was
0.37 (95% CI 0.19-0.55
Results
Small to medium effect on
HbA1c and psychosocial
outcome of educational and
psychosocial intervention.
Identifies need for future
intervention trials
The meta-analysis of the
RCT’S should be treated with
caution due to the variation in
studies and intervention
62 studies in total.
25 RCTs reviewed (16 with
sufficient detail to enable effect
sizes to be calculated).
37 other study designs eg non
RCT’s without control groups,
pre and post intervention
studies
Comments
Rigorous search strategy with
appropriate inclusion criteria.
The effect of educational interventions on metabolic and psychological outcomes in children and adolescents with type 1 diabetes.
Study
Hampson
2001
3.3
compared with 120 age-, sexand duration of diabetesmatched children attending
the Royal Children's Hospital
(RCH) diabetes clinic in
Melbourne
Design
Systematic
review
Level
I
225
Intervention
Animal
insulin
versus
human
insulin.
No studies assessed
these
Others: Complications
Adverse events
Mortality
QOL
Compliance
Cost
Socio-economic effects
Study
Ref No
Population
Intervention
Results
No sig diff.
Hypoglycaemia
Outcome
Results
Parallel designed
studies reported that
human insulin was
associated with a
nonsignificant mean
(pooled weighted
mean difference)
lowering of HbA1c
Outcome
Glycaemic Control:
HbA1c
Fasting BGL
Insulin dose
Treatment of children with type 1 diabetes with insulin glargine
Total patient number 2156.
45 RCT’s (24 parallel and 21
crossover) of which 4 studies
included children.
Population
Patients with diabetes mellitus all
age groups
4.2
Ref No
7
Benefits of animal insulin over human insulin use in children and adolescents with type 1 diabetes
Study
Richter 2002
(Cochrane
systematic
review)
4.1
Comments
Qualitative assessments not reported
Quality of life, mortality and long-term
complications not assessed systematically
in the RCT’s.
Comments
Rigorous search strategy.
Inclusion criteria included diabetic patients
of all ages.
Data collection and analysis performed by
2 independent reviewers.
Significant heterogeneity detected.
Despite heterogeneous study designs
participants and locations neither parallel
or crossover trials suggested an important
difference between insulin species as
measured by glycated haemoglobin,
fasting plasma glucose and insulin dose.
No significant difference in metabolic
control or hypoglycaemic episodes was
found.
Design
Design
Systematic Review
(Cochrane)
Level
Level
I
International Diabetes Federation Consultative Section on Diabetes Education. International Curriculum for Diabetes Health Professional Education. 2002. Brussels, International Diabetes Federation. Ref
Type:Report
Australasian Paediatric Endocrine Group: APEG Handbook on Childhood and Adolescent Diabetes. Sydney, Australasian Paediatric Endocrine Group, 1996
NSW Health Department: Principles of Care and Consensus Guidelines for the Management of Diabetes Mellitus in Children and Adolescents. 1998
Australian Diabetes Educators Association. National Standards for the Development and Quality Assessment of Services Initiating Insulin in the Ambulatory Setting. 2004. Ref Type: Report
2
14
17
18
19
29
Ref No
1
3.4
226
16
4 fully published open label
randomised control trials in
patients with type 1 diabetes.
Seven published abstracts and
One unpublished abstract made
available by manufacture,
three observational studies
4 published RCT’s in type 1
diabetes (and 2 in type 2 diabetes)
Once daily
insulin
glargine
compared
with once or
twice daily
NPH
NICE Health
Technology
Appraisal
No 53
2002
One study found
less nocturnal. hypo
in glargine c/w
once daily NPH.
But similar when
glargine c/w twice
daily NPH.
Nocturnal hypoglycaemia
3 out of 4 studies
found no difference
in HbA1c. One
study found stat.
sig. improvement in
HbA1c with
glargine (trial
duration over only
4 weeks therefore
cannot be attributed
to only glargine)
HbA1c
3 studies reported
severe hypo. One
reported sig less
with glargine. 2
studies no sig
Fourth study did
not distinguish
between nocturnal
and other hypos.
One study showed
no diff.
One study showed
fewer nocturnal
hypoglycaemia in
glargine group
versus NPH group
(36% vs 56%,
p<0.05).
Significantly
decreased FPG in 3
out of 4 studies.
Fourth study
showed no
difference
FPG
Guidance : Recommend that insulin glargine
should be considered as a treatment option in
people with type 1 diabetes
Systematic Review
I
227
27
Sarnblad
2003
18 females, eight males
30 adolescents with T1D (16 in
metformin group and 14 in placebo
group)
Inclusion criteria set to minimise
risk of recruiting type 2 diabetes
subjects
14 in metformin group, 13 in
placebo group
27 adolescents with insulin
requirement >1unit/kg/day and
HbA1c >8%
Population
Type 1 diabetics
oral
metformin or
placebo for 3
months
Intervention
Metformin
versus
placebo for 3
months;
2 month run
in period to
screen for
complications
and update
diabetes
knowledge.
The
metformin (or
placebo)
commenced
at 500mg per
day and
gradually
increased to
max. dose of
1000mg
(wt<50kg)
1500mg(wt<7
5kg) or
2000mg
(wt>75kg)
Ref No
26
HbA1c
Severe
hypoglycaemic
episode in 2
metformin subjects
due to missing meal.
Overall mild
hypoglycaemia was
increased in
metformin group
(p=0.03)
Mean value
decreased
significantly in the
group treated with
metformin, from 9.6
Non sig. trend to
lower BMI in
metformin group
(p=0.35)
BMI
Hypoglycaemia
Metformin group
mena change -0.14
[0.1] versus placebo
+0.02 [0.2]
(p=0.01); significant
decrease
Insulin dose (units/kg/day)
Results
Mean change in
metformin group
-0.3% [0.7]; +0.3
[0.7] in placebo
group (p=0.03);
significant decrease
Metformin group
had mean reduction
-0.9 [3.8] versus
placebo -0.5 [3.2]
(p=0.03); significant
decrease
Outcome
Fasting BGL (mmol/l)
HbA1c
Significance of final HbA1c levels not stated,
but a recalculation shows the mean
difference to be statistically nonsignficant
(mean difference 0.50, 95% CI -1.50 to 0.50)
Compliance:
11 (79%) in metformin group complied with
tablets; 8 (62%) in control group
Compliance was defined as acceptable if
<25% prescribed pills were retunred to
investigators at each visit
3/30 – 1 unwilling to take a second fasting
test; 1 due to gastrointestinal discomfort
(metformin group); 1 due to acute hepatitis
Blinding:
Investigators were blinded to group
allocation
Comments
Randomisation:
computer generated; method of allocation
not reported
Metformin as an adjunct therapy to insulin in the treatment of children and adolescents with type 1 diabetes
Study
Hamilton
2003
4.3
difference
RCT
Design
RCT
II
Level
II
228
Adolescents/young adults(19.3+/3.4yrs) n=10
Type 1 diabetics.
Metformin
250mg BD
(dose
increased to
max of
2500mg/day
depending on
side effects
reported.)
Insulin dose
reduced if
required.
2/10 patients had
one severe
hypoglycaemic
episode
Severe hypoglycaemic
episodes
HbA1c at baseline
3months
6months
Peripheral glucose
uptake divided by
mean plasma insulin
concentration was
increased in
metformin (p<0.05)
but not in placebo
group. Initial insulin
sensitivity was
inversely correlated
to changes in
HbA(1c) (r=-0.62;
p<0.05) and
positively correlated
to changes in insulin
sensitivity (r=0.77;
p<0.01)
HbA1c decreased in
7/10 patients (not
statistically
significant).
Peripheral insulin
sensitivity (euglycaemic
hyperinsulinaemic clamp)
at baseline and at end of
study
[1.0] to 8.7 [1.5] %
(P<0.05), but was
unchanged in the
placebo group (9.5
[1.2] vs 9.2 [1.3]%)
No comparative pre-treatment hypo
information given (although authors say this
translates to approx 40 per 100 patient years)
Very small sample size.
Not randomised, no controls (results
compared to own pre-treatment HbA1c)
Side effects:
1 patient in metformin group had nausea and
mild abdominal pain during study, 1 had
mild abdominal discomfort at final
examination; 5 in placebo group had
gastrointestinal symptoms near start of
study, 1 had stomach pain throughout study
In 1 patient (metformin group), sensitivity
not measured due to technical problems
4/30 – 2 patients excluded at randomisation
due to low HbA1c; 1 patient excluded due to
low motivation (many missed doses); 1
patient left study due to nausea
Blinding:
All patients and investigators were blinded
Randomisation:
Method not stated
Case series (pre -test
and post-test)
IV
National Institute for Clinical Excellence. Type 1 Diabetes (Childhood): Diagnosis and Management of Type 1 Diabetes in Children and Young People (DRAFT). 2004.
28
Initial
metformin
dose 500mg
daily for 1
week,
followed by
500mg twice
daily for 3
weeks, then
1000mg twice
daily for rest
of
study
period
13
29
30
31
Ref No
1
4.4
Gomez 2002
daily insulin dosage 1.2 [0.3] U/kg
mean glycated haemoglobin
(HbA(1c)) 9.3 [1.2] %
mean age =17.0 [1.6] years
229
2
3
Craig 2002
Mortensen
1997
Blood samples and
information were
collected from March
through August 1995 on
2,873 children who
were born in 1977 or
later and seen in the
outpatient clinics.
22 paediatric
departments from 18
countries in Europe,
Japan, and North
America.
1190 children and
adolescents aged 1.215.8 years with type 1
diabetes, identified from
three hospital-based
paediatric diabetes
units, four private citybased paediatric
practices and 18
regional outreach
clinics in NSW and the
ACT from 1 September
to 31 December, 1999
Population
HbA1c levels were
determined once and
analysed centrally
(normal range, 4.4-6.3%;
mean, 5.4%).
Survey
Year of birth, sex,
duration of diabetes,
height, body weight,
insulin regimen, and
number of episodes of
severe hypoglycaemia
during the past 3 months
were recorded.
HbA(1c) level and
incidence of severe
hypoglycaemia
Outcome
Cross sectional audit
Intervention
Ref No
Relationship of number of daily insulin injections with glycaemic control.
Study
5.1
Chapter 5: Insulin Regimens and delivery
Girls on four or more injections had
significantly (P < 0.01) higher BMI than girls
Adolescents on four or more injections
received significantly (P < 0.001) more
insulin.
No difference in glycaemic control was found
among adolescents treated with two, three, and
four or more daily injections.
HbA1c increased during maturation for both
sexes.
Sixty percent of the children (n = 1,707) had
two injections daily, while 37% (n = 1,071)
were on three or more.
The incidence of hypo, based on the 3-month
period, was 22 per 100 patient-years.
Hypoglycaemia (unconsciousness and/or
seizures) was related to younger age (0-8
years) and lower HbA1c level.
Significant predictors of hypoglycaemia in a
Poisson regression model were younger age (P
= 0.03), male sex (P = 0.04), longer diabetes
duration (P = 0.02), and > 3 daily insulin
injections (P = 0.02), but not HbA(1c) level.
Average HbA1c was 8.6 +/- 1.7%, but varied
significantly (P < 0.0001) between centres.
At least one episode of severe hypoglycaemia
in the previous three months was reported in
6.7%, and the rate of severe hypoglycaemia
was 36/100 patient-years.
Significant predictors of HbA1c level in
multiple regression model were: duration and
insulin dose/kg
Results
In multiple
regression model
number of injection
per day was not a
predictor of HbA1c,
but multiple
injections (>3 per
day) was a predictor
of hypoglycaemia.
Australian data..
Comments
crosssectional
clinic data
and
therefore
nonpopulationbased survey
Multicentre,
populationbased, crosssectional
study
Design
IV
Lev
el
IV
230
17
1441 patients with T1D
aged 13-39 years.
726 with no retinopathy
at baseline (primary
intervention group) and
715 with mild
retinopathy (secondary
intervention group)
Conventional therapy with 1 or 2
insulin injections daily and once daily
monitoring (n=704; 352 primary and
352 secondary prevention)
OR
Intensive insulin therapy (by multiple
daily injections or insulin pump) with
frequent BG monitoring (n=704; 348
primary and 366 secondary
prevention)
DCCT 1993
Development of diabetes
complications
Adverse events:
Incidence of hypoglycaemia increase 2-3 fold
on intensive therapy (19 versus 62
hypoglycaemic episodes per 100 patient years,
p<0.001).
Nephropathy:
Intensive therapy reduced risk of
microalbuminuria by 39% (95% CI 21-52) and
albuminaria by 54% (95% CI 19-74);
Intensive therapy reduced the mean adjusted
risk of microalbuminuria by 34% (p=0.04) in
in patients with no retinopathy at baseline and
by 43% in those with mild retinopathy at
baseline (p=0.001)
Neuropathy: At 5 years, intensive therapy
reduced incidence of clinical neuropathy by
69% ; 95% CI 24-87 (3% in intensively
treated group vs 10% in conventionally treated
group) p=0.006 in patients with no retinopathy
at baseline; and by 57% (95% CI 29-73);
p0.002 in those with mild retinopathy at
baseline; combined 60% (95% CI 38-74),
p0.002
on twice-daily insulin.
Retinopathy: intensive therapy reduced the
risk of retinopathy by 76% (95% CI 62-85) in
patients with no retinopathy at baseline
(p0.002), and by 54% (95% CI 39-66) in
those with mild retinopathy at baseline
(p<0.001); combined 63% (95% CI 52-71),
p0.002.
99% of patients
completed study;
>95% of all
scheduled
examinations
completed;
11 patients died;
32 patients assigned
to inactive status for
some time during
trial due to
unavailability or
investigator’s
decision that
continuation of
treatment would be
Research group
blinded to effects of
the two treatment
regimens
Blinding:
Standard therapy
group blinded to
HbA1c results;
intensive therapy
group could not be
blinded to Hba1c
because they were
using it as a
management tool
Landmark study.
Rigorous
multicentre study
supervised by NIH,
USA
See other DCCT
references
Follow up period of
6.5 years (trial
terminated by
independent
monitoring
committee)
RCT
II
231
20
Bougneres
1993
186 patients aged 10-18
yr with IDDM, who
were previously treated
with two daily insulin
injections, were
included without any
selection into a
randomized trial (1
year).
Of 195 adolescents in
the DCCT adolescent
cohort, 175 (91%)
participated in EDIC
(Epidemiology of
Diabetes Interventions
and Complications)
HbA1c
They were either switched to three
injections (regular prebreakfast,
regular prelunch, and
[regular+ultralente] predinner) (n=91)
remained on two injections
([regular+intermediary] prebreakfast
and predinner) subcutaneous
OR
Diabetes complications
Observational four year follow up
from close of DCCT (DCCT =
Intensive insulin therapy and multiple
daily injections with frequent BG
monitoring
OR
insulin injections daily and once daily
monitoring)
18
White 2001
(EDIC follow
up of DCCT
adolescent
cohort)
Retinopathy
The prevalence of worsening retinopathy and
of progression to proliferative or severe
nonproliferative retinopathy were reduced by
74% (p <.001) and 78% (p <.007),
respectively, in the former intensive therapy
group compared with the former conventional
group.
GHb, decreased from 9.8 +/- 0.1 to 9.3 +/0.2% (P < 0.05) in the three-injection group,
whereas it increased from 9.5 +/- 0.3 to 9.8 +/0.3% (P < 0.05) in the two-injection group,
resulting in a modest (0.75%) but significant
difference (P < 0.05) between GHb change in
the two groups. The difference reached 1.4%
(P < 0.0002) in patients with GHb > 11.2% at
entry.
Concluded that even though the diff. between
HbA1c lessened during EDIC, the benefit of
intensive therapy still persisted.
The subsequent first 4 years of EDIC mean
HbA1c was similar for former intensive and
former conventional groups (8.38% vs
8.45%).
HbA1c
During 7.4 years of DCCT mean HbA1c was
lower with intensive therapy than
conventional therapy (8.06% vs 9.76%; p
<.0001)
19 primary refusals
Randomisation:
table of random
numbers
Multicentre
INSERM study
centres in France.
Blinding:
Retinopathy
assessors were
blinded to the
DCCT assignment
of participants
Compliance:
Average time spent
receiving assigned
treatment = 97%,
including 95 women
assigned to
conventional
therapy who
received intensive
therapy during
pregnancy or while
planning a
pregnancy
Rigorous study.
Supervised by NIH
(see other entries for
DCCT).
hazardous
RCT
RCT
II
II
232
Frequency of severe
hypoglycaemia and
DKA
BMI between 3rd & 60th
percentiles for age and sex.
Population
50 type 1
diabetic children
(3-18 yrs)
Mean age 11.5 [3.5]
2nd group of 25 children (randomised
then crossed over to opposite)
C: 12.7 mm in arm
D: 8 mm in arm
1st group of 25 children (randomised
then crossed over to opposite)
A: 12.7 mm in thigh
B: 8 mm in thigh
Intervention
2 injections performed on each child on 2
groups of children.
Ref No
30
Outcome
Frequency of
intramuscular
injections by
ultrasonography
Conclusion: 8mm needles
significantly reduce risk of IM
injections in slim or normal
weight diabetic children and
Significant reduction with 8mm
needle
p < 0.01 arm
p< 0.001 thigh
38% of injections
with 8mm needle were in muscle
(48% in the arm and
28% in the thigh region).
Results
With 12.7 mm needles 86% of
injections were
intramuscular (88% in arm, 84%
in thigh)
Compliance:
Dietary compliance
assessed by
dietician or
physician who was
minimally involved
in direct patient
management – this
was assessed by
dietary recall
after randomisation
(not included in
analysis);
14 secondary
refusals during trial,
where patients
asked to be
switched to the
other regimen (this
part analysed by
intention-to-treat)
All measurements
(using ultrasound)
were performed by the
same operator
25 children received
injection in the thigh,
25 in the arm; method
of selecting injection
site not stated
Order of injections
with different needle
lengths was
randomised
Comments
Open label crossover
study
There were 205 enrolled, 19 primary refusals
following randomisation and these patients
were excluded from the analysis .Of the
remaining 186 patients there were no
differences in baseline characteristics.
The frequency of hypoglycaemia and DKA
was similar in the two groups.
The length of needle for the injection for insulin therapy in the treatment of children with type 1 diabetes
Study
Tubiana-Rufi
1999
5.2
injections (n=95).
Design
RCT
Level
II
233
44
49
WeissbergBenchell
2003
NHS NICE
2003
Population
Standardised mean
difference was 0.58 (95%
CI 0.34-0.83) lower in
pump patients. This
represented reduced total
daily insulin dose by 14%
in pump patients
0.95% HbA1c
improvement on CSII (CI
0.8 – 1.1)
Total daily insulin dose
Insufficient data to be
included in meta analysis,
but descriptive trend
towards less
hypoglycaemia, and risk of
DKA was inconclusive
Side effects:
DKA
Hypoglycaemia
Paediatric and adult studies analysed
together
Publication bias assessed by comparing
results from unpublished data from
abstracts presented at major meetings.
All parallel studies pooled without taking
account of individual study design
No distinction made between studies of
different designs and quality.
No published RCTs in the paediatric
Not sufficient data to
include in meta analysis,
but descriptive trend to
decreased total dose on
CSII.
Insulin requirement
Appropriate inclusion criteria used
however details of how inclusion criteria
were applied are not stated.
Articles obtained by searching Medline
PubMed and reference lists of review and
other articles. English studies only.
Side effects not reported
Data examined by 2 reviewers.
Provided an effect size corrected for
possible publication bias
Some statistical heterogeneity between
studies was evident
Appropriate inclusion criteria for selected
articles.
Comments
Search strategy included Medline, Embase
and Cochrane database. Other data from
manufacturer’s and patient support groups.
included paediatric section
Improvement in mean
BGL on CSII of 17.31
mg% (approx 1mmol/l)
with CI of 13.45-21.16.
Mean blood glucose
HbA1c
Standardised mean
difference was 0.44 (95%
CI 0.2-0.63) lower in pump
patients
Results
Standardised mean
difference in BGL was
0.56 (95% CI 0.35 -0.77)
lower in pump patients
HbA1c
Outcome
Mean BGL
Appropriate search strategy and inclusion
criteria used.
Optimised s.c. insulin
injections
Or
Continuous s.c. insulin
infusion CSII
Optimised s.c. insulin
injections
Or
Intervention
Continuous s.c. insulin
infusion
Systematic review of all insulin
pump studies
Age range 2.3-49.8 years, mean
26+/- 10.8years
1547 patients total
52 studies
(12 studies paediatric, 33 adult,
7 mixed adult/paediatric)
Timeframe 2.5 to 24 months.
Overall 301 patients received
insulin pump, 299 received
insulin injections.
12 RCTs
Ref No
43
Children and adolescents with type 1 diabetes and management with insulin pump therapy
Study
Pickup 2002
5.3
adolescents.
Systematic
Review/
Technology
Appraisal
Systematic
review of 52
studies
(mixed study
designs
including
RCTs)
Design
Systematic
review of
RCTs
T
I
Level
I
234
599 patients with T1D
attending diabetes clinics at
Guy’s and St Thomas Hospitals
UK.
Population
Health technology
Assessment., UK.
Intervention
allocation to either near patient testing (NPT)
n=302 (ie HbA1c results available at the time of
consultation)
or not n=297
Ref No
40
Benefits of near patient testing of HbA1c at outpatient visits.
Outcome
Number of management
changes made during
consultation
NPT leads to more
management changes
in this with poor
glycaemic control
In those with good
control: no diff
Results
In those with poor
control: more likely to
have management
changes made if NPT
used; odds ratio 1.75
(95% CI 1.12-2.72)
Blinding:
Administrativc staff
who handed out
tickets to allocate
patients to groups
were unaware of
Comments
Randomisation:
Assignment of
patients to groups
according to
whether number of
ticket given on
arrival was odd or
even.
Design
Quasi-RCT
International Society for Pediatric and Adolescent Diabetes: ISPAD Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Zeist, Netherlands, Medforum,
2000
Study
Grieve 1999
6.1
No other significant adverse events
recorded in either study.
No increase in serious hypoglycaemia;
Number of events too small for statistical
analysis (1 in each group).
Technical reports and Consensus Statements used to formulate the recommendations and principles of clinical practice.
Ref No
1
61
5.4
One study found no
difference in glycated Hbat 6 months follow-up
there was no significant
difference between CSII
and MDI (8.5 vs 8.7%,
p=NS). A second study
found clear benefit on
glycated haemoglobin.after 4 months follow-up
GHb was significantly
lower in CSII than MDI
(8.8 vs 9.6%, p<0.05).
Only 2 RCTs in adolescents.
Glycated Haemoglobin
(GHb)
included adolescent section
which included 2 RCT’s
CSII compared with
MDI
population. All paediatric studies identified
were case series.
which identified 8 paediatric
studies (case series)
Level
III-1
235
Population
1441 patients
with T1D aged
13-39 years.
726 with no
retinopathy at
baseline (primary
intervention
group) and 715
with mild
retinopathy
(secondary
intervention
group)
insulin injections daily and once
daily monitoring (n=704; 352
prevention)
OR
Intervention
Intensive insulin therapy (by
multiple daily injections or insulin
pump) with frequent BG monitoring
(n=704; 348 primary and 366
secondary prevention)
Ref No
1
Outcome
complications
Nephropathy:
Intensive therapy reduced risk of
microalbuminuria by 39% (95% CI 21-52)
and albuminaria by 54% (95% CI 19-74);
Intensive therapy reduced the mean
adjusted risk of microalbuminuria by 34%
(p=0.04) in in patients with no retinopathy
at baseline and by 43% in those with mild
Neuropathy: At 5 years, intensive therapy
reduced incidence of clinical neuropathy
by 69% ; 95% CI 24-87 (3% in intensively
treated group vs 10% in conventionally
treated group) p=0.006 in patients with no
retinopathy at baseline; and by 57% (95%
CI 29-73); p0.002 in those with mild
retinopathy at baseline; combined 60%
(95% CI 38-74), p0.002
Results
Retinopathy: intensive therapy reduced the
risk of retinopathy by 76% (95% CI 6285) in patients with no retinopathy at
baseline (p0.002), and by 54% (95% CI
39-66) in those with mild retinopathy at
baseline (p<0.001); combined 63% (95%
CI 52-71), p0.002.
Benefits of improved glycaemic control on development of microvascular and macrovascular complications.
Study
DCCT 1993
6.2
Research group
Blinding:
Standard therapy
group blinded to
HbA1c results;
intensive therapy
group could not be
blinded to Hba1c
because they were
using it as a
management tool
Comments
Landmark study.
Rigorous
multicentre study
supervised by NIH,
USA
See other DCCT
references
Follow up period of
6.5 years (trial
terminated by
independent
monitoring
committee)
Equipment failure:
NPT – 1 test not
processed
Conventional
testing – 5 tests not
processed
which group was
NPT or not
Doctors and patients
were not aware iof
group allocation
until the time of
intervention, by
which it was
impossible to
reverse the
allocation
Design
RCT
Level
II
236
2
Mean follow up
OR
125 adolescents
with no
retinopathy and
70 with mild
retinopathy
daily monitoring (n=114)
Intensive insulin therapy (n=95)
(by multiple daily injections or
insulin pump) with frequent BG
monitoring
Adolescent
subgroup of
DCCT trial. Age
13-17 years
DCCT 1994
complications
Nephropathy:
Intensive therapy group had 10%
reduction in microalbuminaria (95% CI
–70% to 52%; p=0.745 in those with no
retinopathy; and by 55% (95% CI 3% to
Retinopathy:
Intensive therapy decreased the risk of
retinopathy by 53% (CI 1-78%, p=0.048)
(in those with no retinopathy) and 70% (CI
25-88%, p=0.010) (in those with mild
retinopathy)
Adverse events:
Incidence of hypoglycaemia increase 2-3
fold on intensive therapy (19 versus 62
hypoglycaemic episodes per 100 patient
years, p<0.001).
retinopathy at baseline (p=0.001)
Blinding:
Standard therapy
group blinded to
HbA1c
results;
intensive therapy
group could nto be
blinded to HbA1c as
they were using it as
Compliance:
Average time spent
receiving assigned
treatment = 97%,
including 95 women
assigned to
conventional
therapy who
received intensive
therapy during
pregnancy or while
planning a
pregnancy
Landmark study.
See other DCCT
references
99% of patients
completed study;
>95% of all
scheduled
examinations
completed;
11 patients died;
32 patients assigned
to inactive status for
some time during
trial due to
unavailability or
investigator’s
decision that
continuation of
treatment would be
hazardous
blinded to effects of
the two treatment
regimens
RCT
II
237
3
1441 patients
with T1D
726 with no
retinopathy at
DCCT 1995
7.4 years (for
adolescents)
Development and progression
of retinopathy
Mean HbA1c during DCCT was dominant
predictor of retinopathy progression, and
the risk gradients were similar in the two
groups; a 10% lower HbA1c (e.g., 8 vs.
9%); p=0.042 in those with mild
retinopathy
Independent data
monitoring
committee
determined that
study
results
warranted
terminating trial
after mean follo-up
of 6.5 years (overall)
Landmark study.
See other DCCT
references
No
patients
voluntarily
withdrew;
2 patients died; 2
patients assigned to
inactive status for
some time
>95% of scheduled
examinations were
completed; overall
time spent in
assigned treatment
was 95%;
a management tool;
Research group
blnded to the effects
of the two treatment
regimens;
Investigators and
patients unaware of
outcome data unless
predetermined
‘alert’ criteria (e.g.
development of
retinopathy) were
reached;
Retinopathy
assessed
by
operators who were
unaware
of
treatment group
assignment
RCT
II
238
5
Nathan 2003
Of 1441 patients
who participated
in the DCCT,
1229 patients
participated in
EDIC
(Epidemiology of
Diabetes
1441 patients
with T1D
726 with no
retinopathy at
baseline and 715
with mild
retinopathy
Four year follow up from close of
DCCT
(DCCT = Intensive insulin therapy
with frequent BG monitoring
OR
daily monitoring)
Primary prevention cohort
(intensive insulin treatment n=348
vs conventional standard treatment
n=352)
Secondary intervention cohort
versus standard conventional
treatment n=352)
Convention therapy with 1 or 2
daily monitoring.
OR
Primary prevention cohort
vs conventional standard treatment
n=352)
Secondary intervention cohort
versus standard conventional
treatment n=352)
daily monitoring.
OR
4
DCCT 1996
Follow up period
of 6.5 years.
Patients with
HbA1c levels
<6.5% exclcued
from study
baseline and 715
with mild
retinopathy
B-mode ultrasound of the
internal and common carotid
arteries to measure intimal
thickness (in 1994-1996 and
1998-2000)
complications
In DCCT, as HbA1c was reduced below
8% there were continuing relative
reductions in the risk of complications,
whereas there was a slower rate of
increase in the risk of hypoglycaemia.
Therefore, the DCCT continues to
recommend implementation of intensive
therapy with the goal of achieving normal
glycaemia as early as possible in as many
IDDM patients as is safely possible
Mean progression of the intima-media
thickness sig. less in group that received
intensive therapy during DCCT than in
group that received conventional therapy
(progression of the intima-media thickness
of the common carotid artery, 0.032 vs.
0.046 mm; P=0.01; and progression of the
combined intima-media thickness of the
Although the magnitude of the absolute
risk reduction declines with continuing
proportional reductions in HbA1c, there are
still meaningful further reductions in risk
as the HbA1c is reduced toward the normal
range.
Proportional reductions in HbA1c are
accompanied by proportional reductions in
the risk of complications.
Hazard rates of retinopathy progression
microalb. and neuropathy are continuous
but nonlinear over the entire range of
HbA1c values in all groups.
Recommend: intensive therapy with the
goal of achieving near-normal glycaemia
should be implemented as early as
possible
Total glycaemic exposure was dominant
factor assoc. with risk of retinopathy
progression
7.2%) is assoc. with a 43% lower risk in
intensive gp and a 45% lower risk in
conventional gp.
Blinding:
Assessment of
intima-media
thickness carried out
by a single operator
who was blinded to
As for DCCT
Retinopathy graded
at a central facility
Blinding:
Standard therapy
group blinded to
HbA1c results;
intensive therapy
could not be blinded
to HbA1c because
they were using it as
a management tool;
Research group
blinded to the
effects of the two
treatment regimens
Blinding:
Participants and
clinics blinded to
HbA1c values unless
they reached a
predefined level of
13%, where
unmaksing occurred
to enable treatment
of patient;
Research group
blinded to the
effects of the two
treatment regimens
See other DCCT
references
RCT
RCT
II
II
239
9
Craig 2002
1190 children
and adolescents
aged 1.2-15.8
years with type 1
diabetes,
identified from
three hospitalbased paediatric
diabetes units,
four private citybased paediatric
practices and 18
regional outreach
clinics in NSW
and the ACT
from 1
September to 31
December, 1999
Diabetes complications
HbA(1c) level and incidence of
Observational four year follow up
from close of DCCT (DCCT =
Intensive insulin therapy and
multiple daily injections with
frequent BG monitoring
OR
daily monitoring)
6
White 2001
(EDIC follow
up of DCCT
adolescent
cohort)
Interventions and
Complications)
N = 611
conventional and
n = 618 intensive
therapy.
Of 195
adolescents in the
DCCT adolescent
cohort, 175
(91%)
participated in
EDIC
(Epidemiology of
Diabetes
Interventions and
Complications)
Median HbA1c 8.2% (IQ range 7.6-9.1%)
in both urban and rural group.
Significant predictors of hypoglycaemia in
a Poisson regression model were younger
age (P = 0.03), male sex (P = 0.04), longer
diabetes duration (P = 0.02), and > 3 daily
insulin injections (P = 0.02), but not
HbA(1c) level.
At least one episode of severe
hypoglycaemia in the previous three
months was reported in 6.7%, and the rate
of severe hypoglycaemia was 36/100
patient-years.
Retinopathy
The prevalence of worsening retinopathy
and of progression to proliferative or
severe nonproliferative retinopathy were
reduced by 74% (p <.001) and 78% (p
<.007), respectively, in the former
intensive therapy group compared with the
former conventional group.
Significant predictors of HbA1c level in
multiple regression model were:
duration and insulin dose/kg
Concluded that even though the diff.
between HbA1c lessened during EDIC, the
benefit of intensive therapy still persisted.
The subsequent first 4 years of EDIC
mean HbA1c was similar for former
intensive and former conventional groups
(8.38% vs 8.45%).
HbA1c
During 7.4 years of DCCT mean HbA1c
was lower with intensive therapy than
conventional therapy (8.06% vs 9.76%; p
<.0001)
common and internal carotid arteries, 0.155 vs. 0.007; P=0.02)
Fewer than 25%
achieve the
recommended
HbA1c <7.5%
In multiple
regression model
number of injection
per day was not a
predictor of HbA1c,
but multiple
injections (>3 per
day) was a predictor
of hypoglycaemia.
Blinding:
Retinopathy
assessors were
blinded to the
DCCT assignment
of participants .
Rigorous study.
Supervised by NIH
(see other entries for
DCCT).
patientt’s treatment
assignments
Multicentre,
study
RCT
IV
II
240
Case attainment
based on
Diabetes Register
was 67% of
children in NSW
and ACT.
Audit of 1,190
children with
T1D.
HbA1c
Median HbA1c 8.2% (IQ range 7.6-9.1%)
in both urban and rural group.
Fewer than 25%
achieve the
recommended
HbA1c <7.5%
Confirmed
homogeneity of
metabolic control in
NSW and ACT
regardless of
location,
socioeconomic
status or system of
care.
Multicentre,
study
IV
112 families
eligible, 8
declined to
participate
Population
Children and
adolescents ages
8-13 yrs with T1D
(N=104)
Intervention
low GI diet (GI 77)
versus high GI diet (GI
79)
HbA1c
Hypoglycaemia
Hyperglycaemia
Weight, height, dietary
intake, quality of life.
Outcome
At 3, 6, 12 months
Ref No
6, 16
Mean GI of diets was not different in
the 2 groups despite differences in
Results
No difference in HbA1c at 3 and 6
months. After 12mths flexible low GI
diet pts had significantly better HbA1c
(8.05 vs 8.62, p=0.05). This difference
between groups was significant, even
after adjusting for baseline values
(P=0.05). There were fewer episodes
of excessive hyperglycaemia defined
as >15 /month (35 vs 66%, P=0.006)
and better QOL for children and
parents in flexible-low GI diet. There
were no differences in number of
hypoglycaemic episodes.
15 participants dropped out (14%), 11
from measured CHO diet and 4 from
flexible-low GI diet. Of the 89
Blinding:
Assessor of dietary adherence not
blinded to participant’s diet allocation,
but all other data nalysis performed by
another researcher blinded to diet
allocation
Comments
Randomisation:
Computer-generated random numbers,
method of allocation concealment not
stated
Design
RCT
Level
II
American Diabetes Association: ADA position statement. Urine glucose and ketone determination. Clinical practice recommendations 1995. Diabetes Care 18(suppl):20, 1995
Coster S, Gulliford MC, Seed PT, Powrie JK, Swaminathan R: Monitoring blood glucose control in diabetes mellitus: a systematic review. Health Technology Assessment 4:1-93, 2000
2000
Ambler G, Barron V, May C, Ambler E, Cameron F: Caring for Diabetes in Children and Adolescents. A parent’s manual. Sydney, Combined Children's Diabetes Services of NSW, 2001
Low glycaemic index diets in the management of type 1 diabetes in children and adolescents
Study
Gilbertson
2001 &
Gilbertson
2003
7.1
Compared urban with rural
children.
10
43
Ref No
11
12
13
15
39
6.3
Handelsman
2001
241
17
14 studies, 356
subjects (203 with
type 1 diabetes,
153 with type 2
diabetes)
Meta-analysis of
RCT’s to
determine whether
low-GI diets,
compared with
conventional or
high-GI diets,
improved overall
glycaemic control
in individuals with
diabetes, as
assessed by
reduced HbA(1c)
or fructosamine
levels
low-GI diets, compared
with conventional or
high-GI diets diets
(average GI difference
22 (range 2-37))
Glycaemic control (HbA1c
and fructosamine level)
Brand Miller
2003
macronutrient intake and
food choice with the use of
3-d food diaries
In the 8 studies in which HbA1c was
determined the low GI diet has a small
but clinically useful effect on
medium-term glycaemic control in
patients with diabetes. (decrease of
HbA1c of 0.43%, CI 0.72-0.13)). If
final HbA1c values were adjusted for
baseline values the mean difference
was reduced to -0.34 units (CI -0.64 to
-0.05 assuming independence.
Children with diabetes who receive
low-GI dietary advice do not report
more limited food choices or a diet
with worse macronutrient composition
than do children who consume a
traditional carbohydrate-exchange diet
After 12 mo, intakes of dietary fat ,
carbohydrate, protein, total sugars,
and fibre did not differ significantly
between the CHOx and Low GI
groups, respectively
no differences in reported
macronutrient intakes during any of
the recording periods.
dietary instruction (GI 77 vs 79). The
differences therefore could not be
explained on GI of the 2 dietary
approaches. Findings suggest dietary
instruction based on flexible low GI
has benefits over weighed CHO
exchange dietary advice.
Many studies involved less than 25
Studies not specific for children or T1D.
Only 2 included children with T1D
One study included 104 children with
type 1 diabetes.
Conclusion was low-GI foods in place
of conventional or high-GI foods has a
small but clinically useful effect on
medium-term glycaemic control.
Only 1 study gave SD’s for individual
low-GI or high-GI differences and these
data were assumed for the statistical
analysis of remaining studies.
Inclusion criteria included: English
studies, 1981-2001, properly
randomised, cross-over or parallel, type
1 or 2 DM, identified in Medline using
“glycemic index” in title.
Intent-to-treat analysis performed on
assumption subjects adhered to dietary
advice provided at entry to study.
completing the study, 4 did not complete
a food diary at 6 months and 6 dod not
complete one at 12 months
Meta-analysis
of RCT’s
I
242
18
7 children with
type 1 diabetes;
6 males, 1
female
Average age 12
± 2 years
Low GI versus high
GI diet (over 6 weeks
for each, separated by
a week interval)
Cholesterol
Glycaemic index
Reduced after low GI diet but not
after high GI diet (final figures
and statistical sig-nificance not
given for the comparison of high
and low GI diets)
Mean GI for low GI diet 68.7
[sem 2.5] versus 81.5 [sem 1.1]
for high GI diet, p< 0.005
Participants received dietary advice
on an individual basis to maximise
adherence
Adherence:
None reported
Blinding:
Not feasible for participants
Randomisation:
Crossover – order of diets
randomised;
Method of randomisation not stated
subjects and were of short duration
Ref No
4
Of 711
intensively treated
subjects in the
DCCT, 687
subjects enrolled
Population
DCCT population
– adults and
adolescents
Self reported retrospective
dietary behaviour
Intervention
84 item questionnaire to
determine whether specific
diet-related behaviours
practised by T1D patients in
intensive treatment group of the
DCCT were associated with
lower HbA1c values.
Study
Delahanty
1993
HbA1c
Outcome
Over-treating hypoglycaemia
and consuming extra snacks
Those who adhered to
prescribed meal plan >90% of
time had average HbA1c 0.9%
lower than subjects adhering
Results
Adherence to prescribed meal
plan and adjusting food and/or
insulin in response to
hyperglycaemia were
associated with lower HbA1c
levels.
Survey instrument pretested with 101
intensively treated participants in the
feasibility stage
Comments
623 of 687 (90%) potential participants
completed the questionnaire
7.2 Adjusting insulin dose for carbohydrate quantity in the management of type 1 diabetes in children and adolescents
Collier 1988
All were
randomised
crossover or
parallel
experimental
design of 12 days
to 12 months
duration (mean 10
weeks) with
modification of at
least 2 meals per
day.
Design
RCT
RCT
(Crossover)
Level
IV (for
this
outcom
e)
II
243
7
6 month and 1
year follow up
Mean age 40
(SD9)
Mean diabetes
duration 16.6 yr
(SD9.6)
169 adults with
T1D in secondary
care clinics in 3
English health
districts. Subjects
had moderately to
poor diabetes
control (HbA1c
7.5-12%) and
duration of
diabetes > 2 years.
DAFNE is adult education in
flexible, intensive insulin
management.
Randomised to receive training
immediately (n=69) or later (in
6 months (n=72)
Training in (DAFNE) dose
adjustment for carbohydrate
intake.
Unchanged – severe
hypoglycaemia in 12/67 vs
11/72 (p=0.68)
ADDQoL significantly
improved in immediate trained
subjects after 1 year (t=2.9,
P<0.01)
Impact of diabetes on
quality of life (ADDQoL)
Impact of diabetes on dietary
freedom improved in
immediate trained group (t=5.4,
P<0.0001)
Severe hypos
HbA1c
Population
10 patients
with insulin
dependent
diabetes
Age 7-12
USA
Trial length: 2 days
Intervention
Sucrose-free diet (2% calories
from sucrose)
vs.
Sucrose-containing isocaloric
diet (10% calories from
sucrose)
Ref No
21
Results
No significant differences:
Area under the glucose response
curve -3672 +/- 240 mg/dl per hr (Sucrose-free)
vs. 3575 +/- 285 mg/dl per hr (Sucrose-containing)
p=0.74
No difference in urinary glucose 35.6 +/- 7.5 (Sucrosefree) vs. 34.5 +/- 7.5 gm/day (Sucrose containing) p=0.84
Urinary glucose
Blinding:
Not stated
Randomisation:
Method not stated
Comments
Crossover design:
participants
received both
diets, each for 2
days
consecutively, in
random order
1016 letters sent, 423 replied, 299 expressed
interest in study, 169 randomised, 27 did not
participate after randomisation so intention
to treat analysis was not possible.
Possible bias in that groups consisted of
volunteers.
Relevance to children is debatable.
Randomisation:
computer generated random number list.
Allocation by use of sealed opaque
envelopes in consecutive order
Outcome
Change in blood glucose
(18 measurements per day)
The effect of moderate use of sugars on glycaemic control in children and adolescents with type 1 diabetes
Study
Loghmani
1991
7.3
DAFNE
study group
2002
Adjusting insulin dose for meal
size and content and consistent
consumption of an evening
snack were assoc. with lower
HbA1c (p<0.03 for differences
between responding <50%,
=50% or >50% of the time)
Sig. better in immediately
trained DAFNE patients than
those trained after 6 months
(mean HbA1c 8.4% vs 9.4%,
(t=6.1, P<0.0001).
beyond the meal plan were
associated with higher HbA1c
levels.
Design
RCT
RCT
Level
II
II
244
23
Schwingshan
dl 1994
(28 patients
initially gave
consent)
24 type 1
diabetes
patients
Age 8-26
Austria
9 patients with
type 1
diabetes
Age 11-16
USA
All subjects rendered
euglycaemic with insulin clamp
overnight prior to study, then
placed on 0.35 mU/kg/min
insulin infusion during 4 hour
intense study period to see
effect of sucrose in diet.
Sucrose free diet (n=11)
vs.
Sucrose (5%) containing diet
(n=13)
Trial length: a mean period of
observation of 83 days (range
42-127 days)
Sucrose (2% ) free diet
vs.
Sucrose (17%) containing diet
22
Rickard 1998
HbA1c
glucose response
No significant difference:
9.0% (sucrose diet) vs.
9.1% (sucrose free diet)
Higher glycaemic response to low sucrose diet attributed
to increased starch content.
Peak glucose response was approx 1 hour earlier (p<0.01)
and was lower (p<0.01) with sugar-containing diet than
with sugar-free diet
Significant difference:
Area under the glucose response
curve 37 +/- 3.5 (SEM) mmol/L (sucrose-free) vs.42 +/4.7 mmol/L (sucrose containing) P=0.01.
Losses to followup:
Data from 4
children excluded
from analysis (3
Blinding:
Not stated
Blinding:
Not stated
Randomisation:
Pseudorandomised –
patients allocated
to treatment
gropups based on
their ability to
attend hospital on
one of two days
for dietary
assessment
Randomisation:
Method not stated
Results should be
regarded as
preliminary due to
small study size,
short duration and
limited power to
detect differences
Crossover design:
participants
received both
diets, each for 2
days
consecutively, in
random order
All mealtimes
monitored by one
of the researchers
to verify that the
correct food was
served and eaten
QuasiRCT
RCT
III-1
II
245
Sucrose (7%) added to
snacks (n=8)
vs.
Sucrose free (1%) (n=8)
Oatmeal alone (OM)
vs.
Oatmeal + sucrose (OMS)
vs.
Oatmeal + protein (OMP)
vs.
Oatmeal + protein + sucrose
(OMPS)
Trial length: 4 successive
Saturdays
Mean blood glucose
Change in blood glucose
No significant
difference:
8.8 nM (sucrose
group) vs.
7.4 nM (sucrosefree)
on day 5
Study suggests a small amount (up to 14%) of simple
sugar replacinfg a portion of complex carbohydrate may
not cause an exaggerated glycaemic response
Combined peak times of breakfasts without added protein
and fat (mean 37.5 [SEM8] min (SEM) vs 54.4 [8] min,
p<0.05 for breakfasts with added protein and fat.
No significant differences in peak glucose values, change
of rise, glucose area under the curve (p>0.05).
Blinding:
Membership of
each group
unknown to
patients, dieticians
and physicians
Blinding:
Not reported
Randomisation:
Method not stated,
hiowever snacks
were colour-coded
by a third party
Randomisation:
Latin square,
where patiets were
randomised to
four different
breakfasts on four
different days
RCT
RCT
II
II
American Diabetes Association: Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care 26 Suppl 1:S51-S61, 2003
NHMRC. Dietary Guidelines for Children and Adolescents in Australia incorporating the Infant Feeding Guidelines for Health Workers. 2003. Ref Type: Report
Franz MJ, Bantle JP, Beebe CA, Brunzell JD, Chiasson JL, Garg A, Holzmeister LA, Hoogwerf B, Mayer-Davis E, Mooradian AD, Purnell JQ, Wheeler M: Evidence-Based Nutrition Principles and
Recommendations for the Treatment and Prevention of Diabetes and Related Complications. Diabetes Care 25:148, 2002
37
Ref No
1
2
3
16 type 1 diabetes
patients
Age 16-39
USA
8 IDD patients
Age 7-16
USA
25
Wise 1989
7.4
24
Wang 1991
Patients in both
groups receievd
dietary education
from the sdame
dietician
First 8 volunteers
selected.
because food
records unusable,
1 because blood
sampling was not
possible)
246
7
Mosher 1998
Population
Adolescents
withT1D were
assigned to groups
with either lower
or higher than 9%
glycosylated
haemoglobin
(HbA1c), and
submitted to 12
weeks of
supervised
training followed
by 12 weeks of
unsupervised
training (n = 12
per group) (age
14.0+/-1.2 years)
Duration of
diabetes 5.0+/-3.1
years.
10 male
adolescents with
T1D (aged 17.2+/1.2 years) and 10
adolescent
nondiabetic (ND)
subjects
(19.4+/1.3years).
Mixed endurance and
calisthenic/strength activities
performed at a rapid pace three
times weekly for 12 weeks
Intervention
12 weeks of supervised training
followed by 12 weeks of
unsupervised training (n = 12
per group).
Ref No
6
No selection protocol
indicated.
Data analysed using a 2x2
analysis of variance
(ANOVA) for repeated
measures.
Did not follow up after study
period to see if benefit was
maintained
Only one subject with IDDM experienced
hypoglycaemia after a single exercise
session.
Both subject groups improved their
cardiorespiratory endurance (p < .05).
Lean body mass of T1D subjects increased
by 3.5% (p < .05). Subjects with and without
T1D lowered their percent body fat (p < .05
and .001, respectively).
Strength improvement of IDDM subjects
ranged from 13.7% (p < .001) to 44.4% (p <
.01), depending upon the manoeuvre.
Fasting blood plasma glucose for all subjects
was unchanged by training, but glycosylated
haemoglobin A1c of T1D subjects was
reduced by 0.96 percentage point (p < .05).
Reductions of HbA1c benefited subjects
with poor preconditioning glycaemic control.
Hypoglycaemia
Cardiorespiratory
endurance
Lean body mass
Strength
Fasting blood plasma
glucose and HbA1c
Comments
Patients were selected from
clinic patients.
Short term training
programme (12 weeks) only
The average levels of HbA1c in poorly and
well controlled diabetic patients were not
affected by training (p<0.05) , a finding
indicating that irrespective of the quality of
glycemia prior to exercise training,
glycaemic control in adolescents with T1D
does not improve in response to exercise
training alone
Aerobic capacity in untrained group
remained stable for the duration of the study
(p<0.05)
Results
Supervised training caused a 17% rise in the
patients' aerobic capacity which during the
ensuing period of unsupervised training
decreased to pre-training levels (p<0.05),
thus suggesting a poor compliance with
unsupervised training.
HbA1c
Outcome
Aerobic capacity was
estimated by Aerobic
Power Index submaximal
test using an ergomedic
818 exercise bike.
Long-term effects of physical activity in children and adolescents with type 1 diabetes
Study
Roberts 2002
8.1
Pretest,
posttest
interventi
on trial
with
control
group
Design
Pre test
and post
test
IV
Level
IV
247
Peak aerobic capacity
HbA1 and FBG
The experimental group significantly (P less
than 0.05) increased their peak aerobic
capacity when compared with baseline
values (47.14 +/- 1.94 versus 50.69 +/- 1.30).
Did not follow up after study
period to see if benefit was
maintained
Not stated, but patients were
required to attend at least
75% of exercise classes to be
be included in the final
analyses
Blinding:
Not stated
Randomisation:
Method of randomisation not
stated
Population
745 Finnish
children at
diagnosis of
T1DM
Intervention
Ref No
2
Outcome
Frequency of DKA
Results
Higher rate of DKA in those
aged < 2 years or > 10 years (<
2 years: 53.3%; 2-10 years:
16.9%; > 10 years: 33.3%).
Children from families with
poor parental educational level
had DKA more often than those
from families with high
parental education (24.4% v
16.9%, p<0.05).
DKA less common in those
with residual insulin secretion
(serum C peptide > 0.10
nmol/L), p<0.05
Aetiology, epidemiology, risk factors, cerebral oedema and management of diabetic ketoacidosis
Study
Komulainen
1996
9.1
Comments
RCT
Design
Cross sectional
Experimental group of children
(N = 9) took part in a 30-min
vigorous exercise program
three times a week for 12 wk;
the control group (N = 10) did
not
Ref No
2
4
9
Children aged 511 yr with T1D
8
Low-density lipoprotein cholesterol was
decreased in subjects with IDDM (p < .05),
but not total cholesterol or triglycerides.
The experimental group significantly (P less
than 0.05) decreased their HbA1 and FBG
while the control group showed no change.
8.2
Campaigne
1984
Lipids
Level
IV
II
248
4
5
6
7
8
11
Yki-Jarvinen
1984
Christensen
1974
Barnes 1978
Bolli 1979
MacGillivray
1982
Pinkey 1994
13 T1DM patients
with DKA (Group
A - severe
ketoacidosis, n =
5, Group B
(moderate
ketoacidosis, n =
8),
38 healthy T1DM
patients, 25
patients with acute
ketoacidosis, 20
non diabetic
controls.
Population-based
5 pituitary-ablated
T1DM patients
and 5 T1DM
patients with
normal pituitary
function
14 newly
diagnosed T1DM
patients after
disappearance of
ketosis and after 3
months of insulin
therapy; 14 non
diabetic controls
14 patients with
diabetes (10 with
DKA); 23 nondiabetic controls
15 diabetic
subjects with
DKA; 6 non
diabetic controls
Withdrawal of insulin for 12hours in both groups; cortisol
replacement in pituitary-ablated
patients
IV "low-dose" insulin (6-10
U/hour)
3
Barrett 1982
Frequency of DKA
Measurement of diurnal
concentrations of glucose,
regulatory hormones, and
electrolytes were measured
serially over 25 hours
Measurement of plasma
and urinary
catecholamines, before and
during treatment
Measurement of glucose,
ketone bodies, growth
hormone, cortisol at
baseline and 12 hours
Plasma norephinephrine
and ephinephrine levels
Insulin sensitivity (IS) and
hepatic glucose production
measured using
euglycaemic insulin clamp
Insulin resistance (Glucose
clearance rate)
Severe DKA (pH < 7.1 and/or
Patients with DKA had
elevated adrenaline and cortisol
levels, 50% had elevated
glucagon and growth hormone
levels
Mean glucose clearance during
insulin treatment in those with
DKA was significantly slower
than in the controls (half time
of fall in plasma glucose 6.1 +
0.6 vs 0.31 + 0.03 hours,.P <
0.001)
IS, as measured by rate of
glucose metabolism, was 35%
lower in newly diagnosed
T1DM patients compared with
controls (P < 0.005); after 3
months of insulin therapy in
subjects with diabetes, IS was
comparable in both groups.
Plasma norephinephrine levels
were elevated in all DKA
patients and correlatd with
degree of metabolic
decompensation (as measured
by plasma carbon dioxide,
P<0.02). compared with
controls; ephinephrine was
elevated in half of those with
DKA
Delayed onset of
hyperglycaemia and
ketogenesis in pituitary-ablated
diabetics compared with
controls (p<0.05); cortisol
replacement partially increased
glucose and ketone
concentrations
In group A plasma
catecholamines were
significantly higher than in
group B, both before and in the
course of therapy (p<0.05).
Study demonstrated a causal
associaton between elevated
counter-regulatory hormones
and ketoacidosis
Study demonstrated a causal
associaton between
sympathetic activity and degree
of ketoacidosis
Small number of cases but
groups comparable in age,
weight and diabetes duration.
Insulin requirement
significantly lower in pituitary
ablated subjects (p<0.05)
Non-diabetic control group
used for comparison
Not randomised; non-diabetic
control group used for
comparison
Population
Case-control
Cohort study
Case-control
Case-control
Case-control
Case-control
III-3
III-2
III-2
III-2
III-2
III-2
III-2
249
13
15
17
18
19
20
Mallare 2003
Kent 1994
PinhasHamiel 1997
Scott 1997
Flood 2001
Morris 1997
DARTS/
26 young females
with T1DM with a
history of
recurrent DKA
and poorly
controlled
diabetes; matched
control group of
patients with
stable diabetes
Adolescents with
T2M diagnosed
1982 -1995.
USA
Adolescents with
T2M (n=50)
compared with
matched group
with T1DM
247 admissions
with DKA, age <
21 years
Children aged <16
years of age at
diagnosis of type
1 diabetes from
Oulu (Finland, n =
43) and Toronto
(n = 87) during
1984-5
139 new onset
type 1 diabetes
patients; age 0.5
to 18 years; from
1995 to 1998
The prescribed insulin dose and
12
Daneman
1990
cohort of 230
patients with
T1DM aged < 21
years
Associations between
Presumed viral infection
present in 17.8% of cases of
DKA, bacterial infection in
12.9% (these were more
common in children aged < 3
years, p=0.03)
25 (28%) of the 89 patients
DKA was present in >25% of
patients with T2DM
Clinical features at
presentation
Rate and predictors of
DKA
7/ 28 (25%) African-American
adolescents with T2DM
presented with DKA
38% presented in DKA.
Associations: no private health
insurance (odds ratio 3.17 (95%
CI 1.2-8.3) p=0.03); missed
diagnosis (68% in DKA vs
32% where diagnosis not
missed, odds ratio 4.6 (95% CI
1.9-11.7), p=0.001),
5/26 (19%) died during a mean
follow up period of 10.5 years.
Causes of death not certain, but
DKA “probably” caused death
in 2 cases; rates of DKA fell
during follow up into adulthood
Clinical features at
presentation
Mortality, cause of death
Prevalence of DKA, risk
factors for DKA
Frequency of DKA, risk
factors for DKA
bicarbonate < 10) in 16%, mild
DKA (pH 7.10-7.35 or
bicarbonate 10-21 mmol/L) in
10%. One death. Severe DKA
was associated with age < 5
years (p<0.05).
Amongst the Finnish group,
those from multiplex families
had a higher C-peptide
concentration and lower
frequency of ketoacidosis than
those from simplex families (p
< 0.05)
Direct evidence of poor
Only 42/60 had ICA
performed; cases of T1DM
may have been misclassified as
T2DM
Small series, but study suggests
that mortality rate is high for
(female) patients with recurrent
DKA and poorly controlled
diabetes
Case series
Retrospective
cohort study
Case control
study
IV
IV
III-2
IV
III-3
Case control
study /
interrupted time
series
Retrospective
Case Series
IV
III-3
Retrospective
Cohort study
(Case series)
Comparative
Cohort study
based
prospective
cohort study
250
22
23
Musey 1995
Cohn 1997
Admissions to
African American
patients with
newly diagnosed
or established
diabetes:
56 adults, age
37.4 + 1.7 years,
56 episodes of
DKA over 3
months
Urban hospital in
USA
Medical, educational, and
psychosocial interventions
volume of insulin prescriptions
supplied were used to calculate
days of maximum possible
insulin coverage per annum,
expressed as the adherence
index.
21
Golden 1985
89 patients, who
attended a
teaching hospital
paediatric or
young-adult
diabetes clinic in
1993 and 1994.
(mean age 16 (SD
7) years, diabetes
duration 8 (4)
years, and
glycosylated
haemoglobin
(HbA1c) 8.4
(1.9)%)
44 children with a
history of
recurrent DKA
MEMO
Collaboration.
(Diabetes Audit
and Research in
Tayside Scotland.
Medicines
Monitoring Unit)
Prevalence of DKA,
Aetiology of DKA
Incidence of recurrent
DKA
glycaemic control
(HbA1c), episodes of
diabetic ketoacidosis, and
all hospital admissions for
acute complications and
the adherence index were
modelled.
The rate of recurrent DKA
decreased from a pre-referral
mean of 25.2 episodes to a
post-referral mean of 2.6 per
100 patient-months (P
<0.0001).
Metabolic control improved:
HbA1c decreased from 14.1% to
10.7% (P < 0.0001).
DKA decreased whether or not
psychotherapy was used.
Of those with known diabetes,
(75% of DKA episodes), 67%
were due to cessation of
insulin. 50% stopped insulin
due to lack of money to buy
insulin or transportation to the
hospital; 21% stopped insulin
due to lack of appetite; 14%
stopped insulin because of
behavioural or psychological
reasons; 14% because they did
not know how to manage
diabetes on sick days
More females than males were
Adherence index was inversely
related to hospital admissions
for diabetic ketoacidosis (p <
0.001) and all hospital
admissions related to acute
diabetes complications (p =
0.008).
obtained less insulin than their
prescribed dose (mean deficit
115 (68; range 9-246] insulin
days/annum). There was a
significant inverse association
between HbA1c and the
adherence index (R2 = 0.39; p
< 0.001).
Gender differences not likely to
Patient group > 18 years of age,
but sample can be considered
representative for aetiology of
DKA in adolescents (the group
most likely to have recurrent
DKA)
No control group
compliance with insulin
therapy in young patients with
IDDM
Cohort study
Cohort study
(consecutive
series)
Time series
study
IV
IV
III-3
251
25
26
Rewers 2002
Liss 1998
25 children (aged
9-17 years) with
T1DM at least 1
year with DKA
and parents;
Dallas clinic,
USA
Controls: children
with T1DM (no
history of DKA
hospitalization)
and parents n=25
24
al Adsani
2000
hospital with
principal
diagnosis of
T1DM (n = 2,270)
children, aged 018 years, during
1991
59 patients with
T1DM (30 males,
29 females), aged
18 to 30 years, 3
year study period,
Kuwait
1243 children
with T1DM aged
< 19 years from
Denver, Colorado
were followed
from Jan 1, 1996
to Dec 31, 2000
35/88 admissions to hospital
were for DKA; 23 females vs
12 males ,NS: p > 0.05).
Insulin omission was the most
common cause of DKA
(11/35); infection in 2/35
Incidence of DKA was 8/100
person-years and increased
with age in girls (P<.001 for
trend). In multivariate analyses,
stratified by age (<13 vs > or
=13 years), the risk of DKA in
younger children increased
with higher HbA1c (RR, 1.68
per 1% increase; 95% CI 1.451.94) and higher insulin dose
(RR, 1.40 per 0.2 U/kg per day;
95% CI, 1.20-1.64). In older
children, the risk of DKA
increased with higher HbA1c
(RR, 1.43; 95% CI, 1.30-1.58),
higher insulin dose (RR, 1.13;
95% CI, 1.02-1.25),
underinsurance (RR, 2.18; 95%
CI, 1.65-2.95), and presence of
psychiatric disorders (for boys,
RR, 1.59; 95% CI, 0.96-2.65;
for girls, RR, 3.22; 95% CI,
2.25-4.61).
More diagnoses reported by
DKA children than controls
(mean 1.9, SD 1.9 v 0.2, SD
0.4; p0.001)
Majority cases: anxiety,
affective and disruptive
behaviour disorders
88% of cases met criteria for at
least 1 psych disorder v 28%
controls(p0.001)
Self-esteem & social
competence lower among cases
Prevalence and aetiology
of DKA
Psychiatric disorders
(DISC)
Child behaviour checklist
Family Assessment
Measure
Brief symptom Inventory
(parents)
Incidence and aetiology of
DKA
admitted with DKA (n=578 vs
n=444) and recurrent DKA
(23.5% vs 14.2%, p<0.0001);
the largest gender difference
was for adolescents
gender differences
Cases and controls matched on
age, sex, ethnicity
DKA subjects were in poor
control at study entry and
diagnosis as reported by mean
number of hospitalisations and
A&E visits compared with
controls (both p0.001)
be due to differences in
incidence of T1DM (females =
males)
Case-control
Prospective
Cohort study
Retrospective
Cohort (case
series)
IV
IV
IV
252
28
29
30
31
32
Mecklenburg
1986
The Diabetes
Control and
Complication
s Trial
Research
Group 1995
Bode BW
1996
Boland 1999
Levy-Marchal
2001
1,260 children
aged < 15 years at
the time of
diagnosis of
T1DM from 24
centres in Europe
217 patients on
CSII followed for
one year
1441 patients,
aged 13 to 39,
with T1DM for 115 years.
Average length of
follow-up 6.5
years (range 3-9)
26 centres in the
US, 3 in Canada
225 patients using
CSII; compared
with use of
multiple daily
injections in same
patients
75 adolescents
aged 12-20 years
1995 – 1998,
USA
Frederiksborg
County, Denmark.
1960-1979
compared with
1943-1963;
adolescents and
young adults
Treatment with CSII (n=25) vs
multiple daily injections (n=50)
Conventional vs intensive
diabetes treatment
27
Ellemann
1984
Incidence and predictors of
DKA
Incidence of DKA and
hypoglycaemia,
psychosocial outcomes
Incidence of DKA and
Frequencies of infusion
system failure and DKA
rate
Adverse events: mortality,
morbidity, DKA,
hypoglycaemia
Incidence of DKA, risk
factors for DKA
No statistically difference in
rate of DKA between two
groups (1/100 patient years in
CSII and 2/100 patient years in
MDI group, NS)
Odds ratio for DKA in the
under 5 age-group was 1.02
(95%-CI:0.69-1.49) relative to
the older children;
DKA recorded in 11 centres:
significant variation between
centres in the frequency of
DKA (range 26 to 67%)
An inverse correlation between
the frequency of DKA and the
background incidence of
T1DM was found in these
centres
No difference in rate of DKA
between two groups
Amongst intensively treated
patients, the DKA rate was
higher in those treated with
CSII than with multiple daily
injections (3.09/100 patient
years vs 1.39 per 100 patient
years, P=0.003)
No difference in rate of DKA
between two groups (pns)
Families of cases scored lower
on problem-solving and
diabetes-specific
‘warmthcaring’
Incidence of DKA at the county
hospital increased from 60 per
100,000 (1943-1963) to 120 per
100,000 (1960-1979). Mortality
decreased in second time
period. Recurrent DKA was
associated with lower
socioeconomic status.
7 episodes of DKA
Not randomised (patients
selected CSII or MDI)
Highly selected, healthy T1DM
patients who received attentive
clinical management and
frequent health education; so
rates of AE may be different in
children
May not be representative
today due to improved pump
technology and education
See other DCCT references
Stastistical significance not
reported
Cohort study
Cohort study
Cohort study
(interrupted
time series)
RCT
Prospective
Cohort study
Cohort study
IV
III-2
III-2
II
IV
IV
253
34
35
36
Laing 1999
Edge 2001
Glaser 2001
Cases of CE in the
UK, reported
through the
British Paediatric
Surveillance Unit
between October
1995 and
September 1998.
Episodes of DKA
reported by 225
paediatricians
identified as
caring for children
with diabetes,
between March
1996 and
February 1998.
61 children with
DKA and CE,
compared to
children with
DKA and no CE,
181 randomly
selected and 174
children matched
to the CE children
Children with
newly diagnosed
T1DM (n=35)
from 1990-98,
mean age 9.2+/4.1 years, United
Arab Emirates
23 752 patients
with T1DM aged
< 30 years,
diagnosed from
1972-93 and
followed to 1997,
UK
33
Punnose 2002
Logistic analysis for the
factors associated with CE.
Mortality from DKA and
CE
Occurrence of CE 61/6977
(0.9%) hospitalisation for DKA
CE significantly associated
with (compared to randomly
selected group):
Lower initial partial pressure of
arterial carbon dioxide: RR for
each decrease of 7.8 mmHg,
3.4 (95%CI 1.9-6.3) (p < 0.001)
Higher initial serum nitrogen
concentration: RR for each
increase of 9 mg per decilitre
1.7 (95%CI 12-2.5, p = 0.003)
(these were also both
Mortality rate from acute
complications of diabetes were
higher than any other causespecific rates in those aged <
20 years (SMR 273, 95% CI
196 – 381 in males; SMR 281
95% CI 201 – 303 in females);
overall 54% of male and 76%
of female deaths were certified
to DKA
The risk of developing CE was
6.8 per 1000 episodes of DKA
in all patients with diabetes (34
cases of CE and 2940 cases of
DKA)
The risk was higher in newly
diagnosed patients (11.9 per
1000 episodes) as opposed to
patients with established
diabetes (3.8 per 1000), p =
0.039.
Out of the 34 cases of CE 8
resulted in death (24%)
Mortality
Cases of CE and DKA
28/35 (80%) patients presented
with DKA and 28% developed
recurrent DKA in follow up
Incidence of DKA
Large study using BPSU
(British Paediatric Surveillance
System); number of cases may
be under-reported
Age-specific mortality rates not
reported for DKA
Comparative
study with
historical
controls
Cross sectional
(audit)
Population
based cohort
study
Cohort Study/
interrupted time
series
IV
IV
III-3
III-3
254
38
39
40
Edge 1999
Bello 1990
Duck 1988
32 cases of DKA
and brain
The group
included 11 cases
of cerebral
oedema.
Retrospective case
note review of
1006 episodes of
DKA.
Deaths caused by
diabetes in
patients under the
age of 20 between
1990 and 1996 in
the UK from
Office of National
Statistics
(England and
Wales
69 cases of DKA
and CE
37
Rosenbloom
1990
Predictors of brain
herniation
Data for the 11 cases of
cerebral oedema were
compared with 20
randomly chosen cases of
DKA without cerebral
oedema
Death
Risk factors for CE
CE associated with:
Younger age (8.6years vs
13.8years, p<0.05)
Longer duration of symptoms
(49 hours vs 16 hours, p<0.001)
New T1D(8 patients vs 1
patient, p<0.01)
Overall rate of fluid
administration was inversely
Incidence in new onset T1D
was 3.3%, compared with
known diabetics (0.23%,
p<0.05).
116 deaths notified and 83 were
caused by diabetes. The
standardised mortality ratio was
2.3 (95%CI 1.9 to 2.9), highest
for the age group 1 -4 at 9.2
(95%CI 5.4 to 14.7)
DKA or hyperglycaemia was
implicated in 83% (69/83)
deaths in patients under the age
of 20 between 1990 and 1996
in the UK.
CE causes 69% (25/36) of
deaths in children with diabetes
under the age of 12.
Overall frequency of cerebral
oedema was 0.7% of all DKA
cases.
significant when compared to
the control group who were
matched to the CE patients)
Treatment with bicarbonate
was associated with CE: RR
4.2 (95%CI 1.5-12.1) (p =
0.008)
Initial serum glucose and
bicarbonate concentration not
associated with CE
CE appeared to be associated
with younger age and new
onset T1DM
Historical controls used for
comparised
Statistical significance not
reported for most comparisons
Case series
Case series
Retrospective
review of cases,
including
published and
unpublished
reports
Cross sectional
III-3
IV
IV
IV
255
42
43
44
Hale 1997
Durr 1992
Bureau 1980
8 dogs with
7 patients with
uncontrolled
T1DM
Group 1: 119
patients aged 13
months to 30
years, 219
episodes of DKA
(retrospective
review)
Group 2: 40
patients aged 1.5
to 20 years
studied
prospectively
USA
4 children with
T1DM aged < 5
years with DKA
leading to CE
compared to 10
aged matched
controls with DKS
but no CE
USA
Bicarbonate infusion
Group 2: 48-hour treatment
plan to provide the volume of
sodium deficit evenly, with half
the deficit given in the first 42
hours
41
Harris 1990
herniation
Delivery of oxygen to
Correlates of CE (glucose,
sodium, bicarbonate,
vasopressin, haematocrit)
Children with CE vs.
children with no CE:
Weight, serum glucose,
minimum serum sodium,
minimum serum
osmolarity, age, body
surface area, initial serum
sodium, initial serum
bicarbonate
Complication rate, change
in serum sodium as serum
glucose declined
Weight: 13.0 ± 3.7 vs. 9.1 ±
2.2kg (p<0.05)
Serum glucose: 26.3 ± 3.3 vs.
43.1 ±19.7 mmol/l (p<0.05)
Minimum serum sodium: 128.8
± 4.4 vs.142.2 ± 8.9 (p < 0.02)
Minimum serum osmolarity:
265.5 ± 10vs. 296.7 ± 15.3 (p <
0.01)
No difference in initial age,
body surface area, serum
sodium, serum bicarbonate
values
6/7 had evidence of CE on
brain CT scan. Initial CE
correlated with BGL and
inversely with bicarbonate, but
not with other variables
The change in calculated
effective plasma osmolality
predicted the progression of CE
during therapy (using
regression analysis)
Bicarbonate therapy in DKA
correlated with the time of
onset of herniation (r = -0.32, p
= 0.04).
4/40 cases occurred at fluid
intakes < 4L/m2/day.
During treatment, "calculated"
serum sodium concentrations
fell significantly (p<0.05) and
were less than 130 mEq/L in
33% of cases at the time of
herniation
Group 1: complications were
more likely to occur among
patients with a failure of the
concentration of sodium to rise
as glucose declined (P<0.01)
Group 2: Serum sodium
concentration = rose in 55/58
(95%) of episodes as glucose
declined. No patient had a
major complication
Not a human study;however
.Small number of cases
Small number of cases
Case control
Case series
Case control
Cohort study
III-2
IV
IV
III-3
256
46
47
48
Mel 1995
Monroe 1997
Bonadio 1988
Children with
DKA and CE, age
range 1 to 15
years, 1972 to
1992
Victoria, Australia
Children admitted
with DKA during
an 18-month
period (n = 79)
USA
63 paediatric
emergency
department visits
for DKA
USA
153 children
admitted for one
or more episodes
of DKA over 12
years
Age < 19 years
USA
Rapid correction of dehydration
(over 6 hours) with fluid
isotonic for sodium vs.
dehydration over 24h using half
normal saline.
45
Mahoney
1999
experimental
DKA
Pediatric risk of mortality
(PRISM) scores were
significantly correlated with
length of stay
27 patients had serum pH <
7.20 or bicarbonate < 10
mmol/L at admission, 25 (92%)
had persistence of metabolic
acidosis after three hours of
outpatient therapy and were
hospitalized.
36 patients had serum pH >
7.20 or bicarbonate
concentration > 10 mmol/L (at
admission, 34 (94%) had
Predictors of need for
admission for management
of DKA (compared with
outpatient management)
decreased cerebral O2
availability (p<0.05); cerebral
hypoxia contributed to the
brain dysfunction
9 cases of brain herniation;
Severity of acidosis,
hypercapnoea and rate of initial
fluid administration were risk
factors.
None of the children with pH >
7.1 and PCO2 > 20 mm Hg had
brain herniation. In 119 patients
with pH < 7.1 or < 20 mm Hg,
0/32 receiving less than 25
mL/kg, 1/ 42 receiving 25-50
mL/kg, and 8/40 receiving
more than 50 mL/kg of IV fluid
during the first 4 hours of
therapy sustained brain
herniation (p<0.001 for <
50mL/kg vs > 50mL/kg).
Decline in serum glucose
concentration between
admission and onset of brain
herniation was not a significant
predictor of CE (NS)
CE incidence: 0.19% (6/3134)
vs. 0.18% (6/3373)
Hospital and ICU length of
stay, need for ICU
admission
CE
Frequency and predictors
of brain herniation
cerebral tissue
included as such a study could
not be performed in humans but
demonstrates potential harm of
bicarbonate therapy
Case series
Retrospective
case series
Retrospective
case series
Cohort study
IV
IV
IV
IV
257
53
54
55
56
57
Adrogue
1982
Winter 1979
Zipf 1979
Gibby 1978
Wilson 1982
44 patients with
DKA (39/44
IDDM, five
patients are newly
diagnosed)
Mean age 26.8 ±
11.6 years (range
21 adults with
DKA
9 children aged 917
Case report 9 year
old boy
Adults with DKA
without extreme
volume deficit
102 children with
acute
gastroenteritis
Red-cell 2,3diphosphoglycerate (DPG)
concentration; tissue
oxygenation
Length of time in DKA
Total insulin dose required
to treat DKA
DKA was considered
corrected when the pH was
> 7.3, bicarbonate >
15mEq/L and serum
A: No phosphate replacement
B: 1 dose of 15 mmol
phosphate replacement therapy
(given as the sodium salt) at 4
hours
C: 3 doses of 15 mmol
Adverse events
Plasma bicarbonate
increment at 2, 4, 8, 16,
and 24 hours after
admission
Accuracy of clinical
assessment of dehydration,
as judged by subsequent
weight recovery in hospital
11 treated with IV phosphate in
doses (mean 118 mmol; range
83-320 mmol) to maintain
normal plasma phosphate; 10
untreated controls
Potassium phosphate infusion
(20-40 meq per litre of fluid)
Group 1: (n=12) normal saline
infused at ~14 mL/kg per hour
in the initial 4 hours ~7 mL/kg
per hour) during subsequent 4
hours.
Group 2 (n=11), normal saline
was infused at half the rates of
Group 1
49
Mackenzie
1989
resolution of metabolic acidosis
within three hours of initiating
outpatient therapy and were
discharged home.
The relapse rate in each group
was similar.
Degree of dehydration was
overestimated by a mean of
3.2%; leading to unnecessary
hospital admissions and
overtreatment with intravenous
fluid.
Statistically significantly
greater increment in
bicarbonate level from
admission at 4 hours in Group
1 vs Group 2 (3.7 vs 0.7
mmol/L) and at 24 hours Group
1 vs Group 2 (13.2 vs 8.4
mmol/L).
Results suggest that slower
fluid deficit correction with an
isotonic solution results in
earlier reversal of acidosis
Potassium replacement during
treatment of DKA using
potassium phosphate salt.
Despite resolution of DKA he
developed hypocalcaemia,
hypomagnesaemia and
hyperphosphataemia
Transient hypocalcemia (n=6),
transient hypomagnesemia
(n=5), carpopedal spasms (n=1)
Significantly lower red-cell
2,3-DPG concentrations were
found between 2 and 6 days
after admission in controls vs
treated patients; no difference
in tissue oxygenation was
found between groups
No significant difference seen
between groups of admission
biochemical data.
Serum phosphate is slightly
different at outset in the
patients treated with sodium
phosphate compared to
Blinding:
Not stated
Randomisation:
No description of how
randomisation took place.
The phosphate load in
potassium phosphate may cause
low calcium and magnesium
III-3
II
RCT
IV
III-2
III-3
Cohort study
Case series
Case report
Controlled trial
Interrupted
time series
258
58
35 patients with
DKA
IV potassium replacement as
phosphate (4.7 to 28.5 mg/kg,
N = 13) or chloride (N = 13), or
no potassium replacement other
than normal diet (N = 9)
(given as the sodium salt) at 2,
6, and 10 hours
Becker 1983
14–58)
USA
Diagnosis of
DKA: blood pH <
7.25, plasma
glucose > 250
mg/dL,
bicarbonate level
< 14 mEq/L,
serum ketones
positive at a
dilution > 1:2
Serum calcium and
phosphate;
Phosphate excretion
ketones were negative.
untreated controls, but this
difference is not significant.
At 4 hours there was no
significant difference in the
serum phosphate between the
intervention groups. At 8 hours
the serum phosphate level was
significantly higher in group B
treated with 1 dose of 15 mmol
at 4 hours, compared to no
phosphate treatment. The
serum phosphate level
remained raised in the group
but raise was not significantly
for 16 and 24 hours.
At 8, 16 and 24 hours serum
phosphate level was
significantly higher in group C,
treated with 3 dose of 15 mmol
at 2, 6 and 10 hours, compared
to no phosphate treatment.
Time course to development of
DKA did not correlate with any
admission biochemical data.
The rate of correction of
arterial blood pH and the mean
duration of time required to
correct the DKA was no
different in any of the three
groups.
No difference among the three
groups in the total amount of
insulin necessary to correct the
DKA.
No clinical benefit of
phosphate therapy found.
Significantly lower serum
phosphorus concentrations at
24 and 36 hours occurred in
patients treated with phosphate,
significantly more phosphorus
was and excreted during the
first 12 hours of the study than
either of the other two groups
of patients.
The use of phosphorus
Not stated
Cohort study
III-2
259
60
61
Hale 1984
Morris 1986
21 adults with
severe DKA (pH
6.9–7.14)
Mean age;
Bicarbonate:
34 ± 5 years,
Controls; 28 ± 4.
USA
Inclusion criteria:
Plasma glucose
level 250
mg/dL,
Serum testing
acetone + ve at >
1:2 dilution,
Serum
bicarbonate level
15 mEq/L
Arterial pH
6.9–7.14,
Age 15 years.
32 patients with
DKA, age range
15 to 80 years, all
treated with
normal saline and
IM insulin
25 patients, age
range 13 to 84
years, severe
DKA (pH < 7.2,
bicarbonate <
10meq/L)
Hypokalaemia and
hyperkalaemia diagnosis;
potassium requirements
during first 24 hours of
treatment for DKA
Rate of fall of BGL;
change in biochemical
parameters
Primary outcome: overall
rate of recovery of DKA
Secondary outcome:
number of concomitant
complications during
treatment
All patients treated with saline
(8 saline alone; 11 also
received bicarbonate (up to 250
meq), 7 received bicarbonate (>
250 meq)
16 treated with 150 mmol
bicarbonate; 16 treated with
normal saline alone
Intravenous bicarbonate
infused over 30 min: 133.8
mEq for arterial pH of
6.9–6.99, or 89.2 mEq for
arterial pH 7.1–7.14),
Repeated every 2 hours until
pH was 7.15 or more
Comparison: no bicarbonate
therapy
Treatment regimen for all
patients to treat DKA
(irrespective of adjunct
bicarbonate therapy):
Insulin: 0.30 U/Kg body
weight; _ IV bolus, 1.2 IM
injection; then hourly injections
of 7 U IM)
Intravenous fluid as 0.9%
saline or 0.45% saline at 250 to
1000 mL/h depending on
patients’ state of hydration.
59
Soler 1972
supplements did not cause
abnormalities in calcium
metabolism but did not prevent
late hypophosphatemia
3/25 patients had hypokalaemia
(<3.5meq/L) and 5/25
hyperkalaemia (>5.5 meq/L) at
diagnosis
Potassium requirement was
significantly greater in those
receiving higher dose of
bicarbonate
No difference in rate of fall of
BGL; significantly slower fall
in blood lactate, lactate:
pyruvate ratio, and total
ketones in patients treated with
bicarbonate compared with
saline group
Comparison of patients before
and after bicarbonate therapy:
At randomisation there was no
difference in the biochemical
profile between the two groups.
No significant differences were
- seen in the rate of change of
pH, ketone bodies, bicarbonate
levels, and plasma lactate
levels.
No significant differences were
noted in the recovery time in
the two groups in terms of the
number of hours required for
glucose levels to reach 250
mg/dL (4.9 ± 1.3 h vs. 4.2 ± 1.0
h in the bicarbonate vs. control
group respectively) and for
bicarbonate to reach 15 mEq/L
(21 ± 4.3 vs. 21 ± 4.0 h,
respectively)
No statistically significant
differences in CSF glucose,
bicarbonate, pH, lactate and
ketones at three time points (0,
6–8, 10–12 h).
There was no effect of mental
status. Initially there appeared
to be a greater decline in BGLs
No description of selection of
patients (adults).
Randomisation:
No description of method of
randomisation
Blinding:
Not stated
2/34
Ramdomisation:
No description of how
randomisation took place.
Blinding:
Not stated
Not stated
RCT
RCT
Case series
II
II
IV
260
64
65
Edwards
1977
Drop 1977
14 children with
DKA, aged 5 to
17 years, with 18
episodes of DKA
22 children with
DKA, aged 21
months to 16
years
USA
48 patients with
DKA
Rates of hypoglycaemia
and hypokalaemia
Rate of correction of
ketoacidosis and change in
biochemical parameters
Rate of clearance of
ketones and fall in BGL
Treatment with low-dose IM
insulin vs high dose SC or IV
insulin
Treatment with insulin: lowdose IV insulin infusion (0.1
U/kg/hr, n=11) or high-dose
intermittent subcutaneous
injections (1 to 2.2 U/kg/hr,
n=11)
Treatment with 0.1 U/kg/hr IV
insulin infusion vs SC insulin
63
Kitabchi 1976
in the control group compared
to the bicarbonate group,
although this was not
statistically significant.
Frequency of hypokalaemia
(potassium <3.3 mEq/L):
Measured by decline in serum
potassium over time showed no
significant difference with or
without bicarbonate
Episodes of hypoglycaemia: (0
vs. 1 episode respectively) and
total insulin delivery
administered for complete
control (124±22 vs. 92±11
units respectively) did not
significantly differ between the
two groups.
IV fluid therapy over 8 hours
did not significantly differ in
the amount of sodium (33 ± 31
vs. 451 ± 74 mEq), chloride
(333 ± 31 vs. 451 ± 74 mEq),
potassium (67 ± 21 vs. 70 ± 17
mEq), or dextrose (36 ± 11 vs.
40 ± 8 g) administered in the
bicarbonate or treatment
groups, respectively.
Lower incidence of
hypokalaemia in low dose
group; higher rate of
hypoglycaemia in high dose
group; no difference in rate of
drop of BGL or change in other
biochemical parameters (NS)
There were no statistically
significant differences in rate of
correction of ketoacidosis, rate
of reduction of plasma glucose,
or decline in plasma osmolality.
The incidence and severity of
hypokalemia were higher in
patients receiving SC insulin.
Serum ketones persisted longer
in the IV group; “both regimens
of insulin administration are
equally effective”
Randomisation:
Random number table
Blinding:
Not feasible
Statistical significance not
reported for comparison of
hypokalaemia between groups
Randomisation:
described
Randomisation:
described
RCT
RCT
RCT
II
III-2
II
261
67
68
69
70
71
73
Burghen 1980
Umpierrez
2003
Soler 1975
Franklin 1982
Curtis 2001
Linares 1996
Children admitted
with DKA over a
4 year period: 132
patient visits in 45
patients (newly
diagnosed caese
excluded)
Mild DKA (pH >
7.20, bicarbonate
Single case of CE
and DKA
Single case of CE
and DKA
51 patients in
severe DKA
45 adults with
DKA
17 children (mean
age 7.4 years)
with newly
diagnosed T1DM
and DKA; 3
children with
established T1DM
and DKA
32 children with
DKA (range 6.2 to
15.8 years)
Adolescent female with lifethreatening DKA-related CE
who responded to combination
of mannitol and hypertonic
saline.
Mannitol
Time to correction of
acidosis; prediction of
patients suitable for
outpatient management
hyperglycaemia and
acidosis
hyperglycaemia/resolution
of DKA, safety, cost
Hourly SC aspart (n=15) vs 2nd
hourly SC aspart (n=15) vs IV
regular insulin (n=15)
IM insulin (n=18); IV infusion
(n=18); IV bolus insulin (n=25)
hyperglycaemia, ketosis
Low-dose (0.1 U/kg/h) vs highdose (1.0 U/kg/h) insulin
Treatment with “low-dose” IM
insulin (mean dose 0.29 U/kg)
66
Baum 1975
Acidosis was corrected within
6 hours in 33/72 (46%) of mild
DKA episodes vs 3/60 (5%) of
moderate-severe DKA (P <
0.0001)
Acidosis was corrected within
6 hours in 69% of mild and
11% of moderate-severe DKA
(P < 0.0001)
Resolution of CE and
ophthalmoplegia after mannitol
therapy
IM insulin resulted in gradual
fall in blood glucose; 2-hour
plasma insulin values were
“within the range which in
adults has been associated with
a maximum fall in blood
glucose concentration”.
No adverse effects
Reduction in glucose was
slower in low-dose group (P <
0.01)
Reduction in ketones,
bicarbonate, cortisol, and
glucagon was similar in both
groups (NS)
Hypokalemia (K < 3.4 meq/L)
occurred in 3/16 low-dose and
10/16 high-dose patients
No difference between 3
groups in time to correction of
hyperglycaemia, resolution of
DKA, incidence of
hypoglycaemia or length of
hospital stay (NS)
SC insulin was associated with
a significantly lower
hospitalisation cost (p<0.05)
Slower fall in blood glucose
with IM regimen
Authors concluded that initial
laboratory values can help
predict patients who may be
considered for outpatient
management (mild DKA), but
the study decesign cannot
address this adequately because
of retrospective design
This is the first report of the use
of hypertonic saline in the
treatment of cerebral oedema
due to DKA
Not randomised
Abstract only – insufficient
details for critical appraisal
Losses to follow-up: None
reported
Blinding: Not feasible
Randomisation: Method of
randomisation not stated
None reported
No control group
Case series
Single case
Single case
Prospective
cohort study
IV
III-2
II
II
RCT
RCT
III-3
Cohort study
(two single
arms)
262
Management of surgery and fasting in children and adolescents with diabetes
Ref No
3
Population
19 peri operative
children and
adolescents with
type I diabetes
mellitus
Intervention
Intravenous insulin infusion
(n=9, gp 1) versus
subcutaneous insulin (n=10, gp
2)
Study
Kaufman
1996
Outcome
Blood glucose levels
Results
The mean bedside BGL were
higher 1 h prior to surgery and
during the intraoperative period
(p < 0.05) in those receiving sc
insulin.
In the postoperative period,
BGL were higher at multiple
times for up to 3 days in those
treated with sc compared to IV.
To achieve glycaemic control,
insulin dosage needs to be
increased on the day of surgery
and for approximately 2
postoperative days
Infusion give better BGL
control than sc.
Comments
On the day of surgery and
during postoperative days 1 and
2, patients in group 1 received a
greater insulin dosage than
group 2 subjects (p < 0.025). In
group 1, insulin dosage was
increased 23% and 15% over
baseline for postoperative days
1 and 2, respectively, then, by
day 3, was decreased back
toward the baseline.
As only one study was found the majority of the suggested protocol in the Surgery and Fasting chapter is based on consensus.
10.1
Design
Retrospective
case series
Level
III-3
Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TPA, Glaser NS, Hanas R, Hintz RL, Levitsky LL, Savage MO, Tasker RC, Wolfsdorf JI: ESPE / LWPES consensus statement on
diabetic ketoacidosis in children and adolescents. Archives of Disease in Childhood 89:188-194, 2003
American Diabetes Association., Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM: Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care 26
Suppl 1:S109-S117, 2003
2000
72
10
Ref No
1
9.2
>10 mmol/L,
n=60)
Moderate-severe
DKA (pH < 7.20,
bicarbonate < 10
mmol/L, n=72)
USA
263
International Society for Pediatric and Adolescent Diabetes: ISPAD Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Zeist, Netherlands,
Medforum, 2000
Consensus Statements used to formulate the recommendations and principles of clinical practice
11
Collier
1987
52 adult insulintreated patients
attending an
emergency
department with
severe
hypoglycaemia
Population
29 adult patients
attending an
accident and
emergency
department in
hypoglycaemic
coma
Outcome
Recovery after
hypoglycaemia
Recovery after
hypoglycaemia
Intervention
Randomized to
treatment with either
intravenous dextrose
(25g); n=14 or
intramuscular
glucagon (1mg); n=15,
administered into the
right thigh
Intravenous glucagon
(1 mg); n=25 was
compared with
(25 g); n=24
Ref No
10
Consciousness assessed
throughout the study by the
same observer
1 patient with coexisting
Addison’s disease excluded
from analysis (received both
glucagon and dextrose but onoy
regained normal consciousness
after receiving hydrocortisone)
Intravenous glucagon and dextrose were effective
in the treatment of hypoglycaemic coma.
There was a difference in the glycaemic profile
after intravenous glucagon compared with
Recovery of a normal level of consciousness after
glucagon was slower than after dextrose (6.5
(range 2-16) vs. 4.0 min (range 1-15),
respectively; P <0..001).
Although IV glucagon is an option, IM glucose is
faster
Should be balanced against the advantages of
ease of administration and a lower incidence of
serious adverse effects
Two patients in the glucagontreated group, who failed to
show satisfactory recovery after
15 min, required additional
treatment with intravenous
dextrose.
Randomisation:
Method not stated
Small numbers and results and
analysis poorly reported
Adult study
IM glucagon is valuable in severe hypoglycaemia
outside hospital.
The slightly slower and less predictable recovery
may make it a less attractive option than IV
dextrose in the emergency department,.
Comments
Randomisation:
stated
Results
Normal conscious level slower after glucagon
than dextrose (9.0 (range 5-30) vs 3.0 (range 215) min, p <0.01)
Management of severe hypoglycaemia: to treat with intravenous glucose or intramuscular/intravenous glucagon
Study
Patrick
1990
11.1
RCT
Design
RCT
II
Level
II
No studies were identified. One review article was found, others included advice, personal practice. Therefore the regimen suggested in the Sick Day Management chapter is
based on current consensus guidelines.
Insulin adjustment during “sick days”/intercurrent illnesses in children and adolescents with Type 1 diabetes
Ref No
7
8
10.2
264
33 episodes of
impending or mild
hypoglycaemia in
28 children (ages
6.6 ± 0.7 years)
with T1D
Blood glucose was 3.44 ± 0.15 mmol/l before and
8.11 ± 0.72 mmol/l 30 min after glucagon.
In 14 children, relative hypoglycaemia recurred,
requiring retreatment (3.48 ± 0.18 to 6.94 ± 0.72
mmol/l). In four children, a third dose was
required.
The glucagon was well tolerated.
In 28 of the 33 episodes of impending
hypoglycaemia, the children remained at home
and fully recovered. Five children were taken to
their local hospital because of concerns of
dehydration or fever, but none for
hypoglycaemia.
BGL
Recurrence of
hypoglycaemia
Side effects of
glucagon
Need for
admission
Only reported study of its kind
and needs to be repeated in
other centres.
Case series
Ref No
23
Population
Adolescent
subgroup of
Intervention
Intensive insulin therapy
(n=95) (by multiple daily
Outcome
complications
Effects of intensive diabetes management on the incidence of hypoglycaemia.
Results
Retinopathy:
Intensive therapy decreased the
Comments
Landmark study.
Design
RCT
Medforum, 2000
Study
DCCT
1994
12.1
If the blood glucose
did not increase within
30 min, the initial
dosage was doubled
and given at that time.
The patients’ selfglucose monitoring
devices, aqueous
glucagon, standard
insulin syringes, and
frequent phone contact
with a physician
and/or a diabetes nurse
educator were used in
this study.
Using a standard U100 insulin syringe,
children ages 2 years
received two "units"
(20 g) of glucagon
subcutaneously and
those ages >2 years
received one unit/year
of age up to 15 units
(150 g).
Consensus Statements used to formulate the recommendations and principles of clinical practice.
13
Ref No
7
16
17
11.2
Haymond
2001
1 patient had already receieved
subcutaneous glucagon
administered at home by a
relative before arriving at the
emergency dept.
Mini-dose glucagon rescue,
using subcutaneous injections,
is effective in managing
children with type 1 diabetes
during episodes of impending
hypoglycaemia due to
gastroenteritis or poor oral
intake of carbohydrate.
Level
II
IV
265
25
1190 children and
adolescents aged
1.2-15.8 years
with type 1
diabetes,
identified from
three hospitalbased paediatric
diabetes units,
four private citybased paediatric
practices and 18
regional outreach
Craig 2002
Mean follow up
7.4 years (for
adolescents)
OR
125 adolescents
with no
retinopathy and 70
with mild
retinopathy
Conventional therapy with 1 or
2 insulin injections daily and
once daily monitoring (n=114)
injections or insulin pump)
DCCT trial. Age
13-17 years
HbA(1c) level
HbA1c
Episodes of
hypoglycaemia
At least one episode of severe
hypoglycaemia in the previous
three months was reported in
6.7%, and the rate of severe
hypoglycaemia was 36/100
patient-years.
Significant predictors of
HbA1c level in multiple
regression model were:
duration (b = 0.05; 95% CI,
0.02-0.07) and insulin dose/kg
(b = 0.46; 95% CI, 0.27-0.66).
HbA1c (%+/-SE): 8.06+/-0.13
vs 9.76+/-0.12 (reduction of
1.7% +/-SE 0.18)
Severe hypoglycaemia: RR
2.96 (95% CI 1.90-4.62)
Hypoglycaemia resulting in
coma or seizure: RR 2.93
(95%CI 1.75-4.90)
Overweight: RR 2.11 95% CI
1.31-3.40)
Diabetic ketoacidosis: RR 0.2
(95% CI 0..32-1.23)
Nephropathy:
Intensive therapy group had
10%
reduction
in
microalbuminaria (95% CI
–70% to 52%; p=0.745 in those
with no retinopathy; and by
55% (95% CI 3% to 9%);
p=0.042 in those with mild
retinopathy
risk of retinopathy by 53% (CI
1-78%, p=0.048) (in those with
no retinopathy) and 70% (CI
25-88%, p=0.010) (in those
with mild retinopathy)
Fewer than 25% achieve the
recommended HbA1c <7.5%
Independent data monitoring
committee determined that
study results warranted
terminating trial after mean
follo-up of 6.5 years (overall)
In multiple regression model
number of injection per day
was not a predictor of HbA1c,
but multiple injections (>3 per
day) was a predictor of
hypoglycaemia.
No patients voluntarily
withdrew;
2 patients died; 2 patients
assigned to inactive status for
some time
>95%
of
scheduled
examinations were completed;
overall time spent in assigned
treatment was 95%;
Blinding:
Standard therapy group blinded
to HbA1c results; intensive
therapy group could nto be
blinded to HbA1c as they were
using it as a management tool;
Research group blnded to the
effects of the two treatment
regimens;
Investigators and patients
unaware of outcome data
unless predetermined ‘alert’
criteria (e.g. development of
retinopathy) were reached;
Retinopathy assessed by
operators who were unaware of
treatment group assignment
Multicentre,
populationbased, crosssectional study
IV
266
27
29
Davis 1998
DCCT
709 patients were
studied yielding
2027 patient years
of data (mean
(SD) age: 12.3
(4.4); range 0-18
years, duration
IDDM: 4.9 (3.8)
years).
1441 patients with
Rates of severe
(coma,
convulsion) and
moderate
(requiring
assistance for
treatment)
hypoglycaemia
were studied
prospectively over
a four year period
Case attainment
based on Diabetes
Register was 67%
of children in
NSW and ACT.
A large population
based sample of
T1D children and
adolescents.
Audit of 1,190
children with
T1D.
Compared urban with rural
children.
26
Handelsma
n 2001
clinics in NSW
and the ACT from
1 September to 31
December, 1999
Details of hypoglycaemia
were recorded at clinic
visits every three months
when glycated
haemoglobin (HbA1c) was
also measured.
HbA1c
Retinopathy: intensive therapy
This increase was particularly
marked in younger children (<
6 years) in whom severe
hypoglycaemia increased from
14.9 to 42.1 episodes/100
patient years in 1995.
In parallel with this there was
an increase in the rate of
hypoglycaemia, especially in
the fourth year of the study,
when severe hypoglycaemia
increased from 4.8 to 15.6
episodes/100 patient years.
Over the four years mean (SD)
clinic HbA1c steadily fell from
10.2 (1.6)% in 1992 to 8.8
(1.5)% in 1995(p<0.01).
the prevalence of severe
hypoglycaemia (coma or
convulsion) was 36 episodes
per 100 patient years
Incidence of severe
hypoglycaemia was 7.8 and
moderate was 15.4
episodes/100 patient years.
Median HbA1c 8.2% (IQ
range 7.6-9.1%) in both urban
and rural group.
Median HbA1c 8.2% (IQ
range 7.6-9.1%) in both urban
and rural group.
Significant predictors of
hypoglycaemia in a Poisson
regression model were younger
age (P = 0.03), male sex (P =
0.04), longer diabetes duration
(P = 0.02), and > 3 daily insulin
injections (P = 0.02), but not
HbA(1c) level.
Landmark study.
Australian study (Perth)
Attempts to achieve improved
metabolic control must be
accompanied by efforts to
minimise the effects of
significant hypoglycaemia,
particularly in the younger age
group.
Fewer than 25% achieve the
recommended HbA1c <7.5%
Confirmed homogeneity of
metabolic control in NSW and
ACT regardless of location,
socioeconomic status or system
of care.
RCT
All diabetic
children
attending the
Princess
Margaret
Hospital over
4 years were
included. Case
ascertainment
for Western
Australia >99%.
Thus this is a
population
based
prospective
observational
study
Multicentre,
populationbased, crosssectional study
II
IV
IV
267
T1D aged 13-39
years.
726 with no
retinopathy at
baseline (primary
intervention
group) and 715
with mild
retinopathy
(secondary
intervention
group)
once daily monitoring (n=704;
352 primary and 352 secondary
prevention)
OR
multiple daily injections or
insulin pump) with frequent
BG monitoring (n=704; 348
prevention)
1993
complications
Adverse events:
Incidence of hypoglycaemia
increase 2-3 fold on intensive
therapy (19 versus 62
hypoglycaemic episodes per
100 patient years, p<0.001).
Nephropathy:
Intensive therapy reduced risk
of microalbuminuria by 39%
(95% CI 21-52) and
albuminaria by 54% (95% CI
19-74);
Intensive therapy reduced the
mean adjusted risk of
microalbuminuria by 34%
(p=0.04) in in patients with no
retinopathy at baseline and by
43% in those with mild
retinopathy at baseline
(p=0.001)
Neuropathy: At 5 years,
intensive therapy reduced
incidence of clinical
neuropathy by 69% ; 95% CI
24-87 (3% in intensively
treated group vs 10% in
conventionally treated group)
p=0.006 in patients with no
retinopathy at baseline; and by
57% (95% CI 29-73); p0.002
in those with mild retinopathy
at baseline; combined 60%
(95% CI 38-74), p0.002
reduced the risk of retinopathy
by 76% (95% CI 62-85) in
patients with no retinopathy at
baseline (p0.002), and by 54%
(95% CI 39-66) in those with
mild retinopathy at baseline
(p<0.001); combined 63%
(95% CI 52-71), p0.002.
Compliance:
Average time spent receiving
assigned treatment = 97%,
including 95 women assigned
to conventional therapy who
received intensive therapy
during pregnancy or while
planning a pregnancy
99% of patients completed
study;
>95% of all scheduled
examinations completed;
11 patients died;
32 patients assigned to inactive
status for some time during trial
due to unavailability or
investigator’s decision that
continuation of treatment
would be hazardous
Research group blinded to
regimens
Blinding:
therapy group could not be
blinded to Hba1c because they
were using it as a management
tool
Rigorous multicentre study
supervised by NIH, USA
Follow up period of 6.5 years
(trial terminated by
independent monitoring
committee)
268
52 adult insulintreated patients
attending an
emergency
department with
severe
hypoglycaemia
Population
29 adult patients
attending an
accident and
emergency
department in
hypoglycaemic
coma
Outcome
Recovery after
hypoglycaemia
Recovery after
hypoglycaemia
Intervention
Randomized to treatment with
either intravenous dextrose
(25g); n=14 or intramuscular
glucagon (1mg); n=15,
administered into the right
thigh
Intravenous glucagon (1 mg);
n=25 was compared with
intravenous dextrose (25 g);
n=24
Although IV glucagon is an
option, IM glucose is faster
Recovery of a normal level of
consciousness after glucagon
was slower than after dextrose
(6.5 (range 2-16) vs. 4.0 min
(range 1-15), respectively; P
<0..001).
There was a difference in the
glycaemic profile after
intravenous glucagon compared
with intravenous dextrose
Should be balanced against the
advantages of ease of
administration and a lower
incidence of serious adverse
effects
Intravenous glucagon and
dextrose were effective in the
treatment of hypoglycaemic
coma.
The slightly slower and less
predictable recovery may make
it a less attractive option than
IV dextrose in the emergency
department,.
IM glucagon is valuable in
severe hypoglycaemia outside
hospital.
Results
Normal conscious level slower
after glucagon than dextrose
(9.0 (range 5-30) vs 3.0 (range
2-15) min, p <0.01)
Ref No
6
Population
Follow up study
from Northam 98
None
Intervention
Study
Northam
2001
Outcome
WISC-III and subtests of
WISC-III used for IQ,
Results
Six years after onset of
diabetes, children with T1D
Effects of hypoglycaemia on cognitive function in children and adolescents with type 1 diabetes
50
Collier
1987
12.3
Ref No
49
Comments
Subjects enrolled from Royal
Children’s Hospital,
1 patient with coexisting
Addison’s disease excluded
from analysis (received both
glucagon and dextrose but onoy
regained normal consciousness
after receiving hydrocortisone)
1 patient had already receieved
subcutaneous glucagon
administered at home by a
relative before arriving at the
emergency dept.
Consciousness assessed
throughout the study by the
same observer
Randomisation:
Method not stated
Two patients in the glucagontreated group, who failed to
show satisfactory recovery after
15 min, required additional
treatment with intravenous
dextrose.
Small numbers and results and
analysis poorly reported
Adult study
Comments
Randomisation:
stated
Management of severe hypoglycaemia: to treat with intravenous glucose or intramuscular/intravenous glucagon?
Study
Patrick
1990
12.2
Design
Comparative
cohort study
RCT
Design
RCT
Level
III-2
II
Level
II
269
8
Rovet 1997
100 controls (50
boys, 50 girls)
mean age 13.1 +/2.5 years.
103 T1D (50
boys, 53 girls)
Mean age 13.5 yrs
+/-2.3 years)
21 children with
T1D (age 5.511.8yrs) and 10
healthy controls
N/A
Normal controls
WISC-R and WAIS-R IQ
Attentional functioning
NEPSY (dev. Neuropsych
assessment)
T1D and one episode of severe
hypo (n=11)
T1D with no hypo (n=10).
WISC-R
attention, processing
speed. Memeory tested
with RAVLT, Executive
functions with COWAT
Divided into 3 groups
7
Hannonen
2003
study
90 patients (aged
6-17 years, mean
12.1 +/- 2.9) who
had been
previously
assessed soon
after Dx and 2
years later were
re-evaluated 6
years after onset
of diabetes.
84 controls
(12.1+/-2.8 years,
p=NS).
Those with seizure history had
lower verbal IQ than controls
and greater difficulty with
IQ poorer performance in early
onset (p=0.01)
Memory – Digit span
both T1D with & without
hypoglycaemia scored lower
compared with controls
(p<0.01)
T1D attention scores lower in
several but not all aspects of
attention
Phonological processes in T1D
with hypos scored
lower than controls (p<0.05)
Severe hypo assoc. with lower
verbal and full-scale
intelligence quotient scores.
Children with history of severe
hypoglycaemia had more
neuropsychological
impairments (7 of 11) than
without hypoglycaemia (3 of
10).
Attention – T1D
without hypos had test scores
significantly lower
than controls (p<0.05)
Attention, processing speed, &
executive skills were esp.
affected when onset was before
4 yrs old.
performed more poorly than
controls on verbal IQ (F=8.07,
p<0.01), ful scale IQ
(F=5.33.P<0.05) attention
(F=2.63, P<0.05), processing
speed (F=4.81, P<0.01), longterm memory (F=3.58,P<0.01),
and executive skills (F=4.57,
P<0.05).
Patients and controls recruited
from Hosp for Sick Children,
Toronto, Canada.
Comparison between controls
and diabetes subjects were by t
tests and ANOVA’s.
Finnish Study. Clinic patients
with diabetes-otherwise well.
No special selection criteria.
Retrospective history of
hypoglycaemia
Melbourne. Analysis of
variance was used to examine
group differences, effects of
age of onset.
Comparative
cohort study
Comparative
cohort study
III-2
III-2
270
10
39
40
Hershey
1999
Holmes
1985
Sansbury
1997
28 T1D children
41 children with
T1D
16 Children With
Type 1 Diabetes
Mean Age 12.1
+/-2.6 Years
(Range 9.4-17.7
Years)
Mean age at
diagnosis was 4.5
years+/-3.0years.
mean HbA1c
8.4% (range 7.59.4)
Nondiabetic
children (n = 16)
and 25 children
with type 1
diabetes
HbA1c
Duration
Age at onset
Divided in 4 groups depending
upon age of onset and length of
duration
Randomised at diagnosis to
either intensive (IT) (n = 13) or
conventional (CT) (n = 12)
diabetes therapy
Follow up at 1, 3, 7 years
9 had hypoglycaemic seizure
9
Rovet 1999
Behaviour checklist
Matching figures
Verbal subtests
WISC-R
WISC-R
Episodes of severe
hypoglycaemia were
prospectively ascertained.
All children were tested on
memory tasks that have
been closely linked to
medial temporal
functioning and on reaction
time measures
Perceptual, fine motor,
visuomotor, visual memory
and attention
Verbal IQ
Poor metabolic control assoc
with lower vocab subtest
scores.
Inc duration assoc with lower
matching figures score.
Reading and memory
impairment in early onset
groups
Increased age assoc with
decreased IQ score
Larger studies needed, but
extreme caution in imposing
overly strict standards for
glucose control in young
patients with type 1 diabetes
would be indicated because of
the increased risk of
hypoglycaemia associated with
IT regimens.
IQ scores lower in early onset
and longer duration
There were no effects on fullscale IQ, performance IQ,
supplementary spatial or
achievement tests.
IT had a threefold higher rate
of severe hypoglycaemia than
the CT group;
and performed less accurately
on a spatial memory task,
performed more slowly
(p=0.01), but not less
accurately, on a pattern
recognition task than did the
CT group or control subjects.
Hypo seizure patients scored
lower (p<0.01)
some aspects of attention.
At 7 years those with hypo
seizures more likely to have
verbal IQ decline (67% vs
14%, p<0.05)
Comparison with nondiabetic
participants was not
randomised
Randomisation:
stated
The study’s strengths were its
extended time frame and
detailed testing 7 years after
diagnosis. Limiting factors
include small sample size, lack
of longitudinally assessed
controls, and possible bias
within groups and recall
inaccuracies of diabetes data
management.
Cohort study
Cohort study
RCT
Prospective and
retrospective
data collection
IV
IV
II (for
compariso
n of IT
and
CT);
III-3
for
compa
rison
of IT
or CT
with
nondia
betic
contro
ls
IV
271
27
Tubiana-
165 French
Population
88 youths, 8
to 13 years
old at onset of
IDDM
83 were white
(94%), 5 were
black (6%)
Intervention
None
A standardized scale (FACES III) was
Psychiatric diagnoses were derived
independently of HbA1 values
Levels of HbA1 were also assessed
repeatedly.
Outcome
Evaluated repeatedly during a 9-year
follow-up period, on average, using a
standardized psychiatric protocol.
Ref No
16 and 41
During observation period 44 patients (50%) had one or
more episode of psychiatric disorder and 35 (40%)
received the diagnosis of non-compliance with medical
treatment.
More diabetic families than comparison families fell into
According to the final multivariate model of repeatedly
assessed HbA1, non-compliance with medical treatment
(irrespective of duration) and the interaction between nondepressive psychiatric disorder and IDDM duration
contributed to worse metabolic control.
Interaction terms between IDDM duration (or age) and
psychiatric variables were significantly related to
metabolic control.
In univariate longitudinal analyses, the psychiatric
diagnosis of non-compliance with medical treatment was
significantly related to HbA1 level. There was a trend of
an association between any major psychiatric disorder, as
well as non-depressive disorder, and HbA1.
Social competence, self-esteem, and aspects of family
functioning at IDDM onset and initial psychiatric status
did not predict non-compliance. However, noncompliance was associated with having major psychiatric
disorder later in the course of IDDM
Non-compliance tended to emerge in middle adolescence
and was found to be protracted.
Results
The cumulative risk for non adherence over the 9 years
was 0.4
Comments
Sample
derived from
patients
sequentially
admitted to
Pittsburgh
1978-1985.
Approx 75%
of suitable
families were
recruited.
Those who
declined did
not differ
significantly.
The incidence and risk factors for non-adherence with treatment regimens in children and adolescents with type 1 diabetes.
Study
Kovacs
1992 and
1996
13.1
Cross-sectional
Design
Longitudinal
Observational
study.
IV
Level
IV
2000
56
57
Ref No
37
12.4
272
41 children
with T1D
from
paediatric
diabetes
clinic.
28
30
31
32
33
34
Frank 1996
Ott 2000
Hentinen
1992
Burroughs
1993
Kyngas
2000
Littlefield
Diet and monitoring are problem areas
Diet
Participants completed the Rosenberg
Adherence was lowest for diet and home blood glucose
monitoring.
Adolescents reporting lower adherence tended to report
mean age
15yrs
193
Compliance with insulin treatment 81%.
Compliance
Only 19% reported complete compliance with all aspects
of diabetes management.
Dietary compliance is best predictor of metabolic control
Co-operation
Predictors of compliance
Monitoring
Showed best adherence
Self efficacy was the mediating variable for mastery
experiency
Family adaptation significantly and positively correlated
to parent’s education level.
Compliant patients more likely to have tertiary education,
fewer hospitalisations
the categories of disengaged with low levels of cohesion,
and rigid with low levels of adaptability. Scores of
cohesion and adaptability were significantly and
positively correlated with both children's and parents'
adherence scores, but not with HbA1c levels. Children
from rigidly disengaged families had a more
hypoglycaemias and 6 times more ketoacidosis than the
other diabetic children.
Parental responsibility
Insulin treatment
Personal responsibility
Adherence
Self-efficacy
Compared compliant with non
compliant patients
used to determine if family cohesion
and adaptability (i) differed in diabetic
children's families, as compared to
other families; (ii) were related to an
adherence measure; or (iii) were
related to metabolic control.
21
adolescents
aged 13-18
yrs
289
adolescents
with T1D.
age 13-17 yrs
47 children,
Finland
Mean age
21.7 +/-0.55
143
adolescents
with T1D
Canada
diabetic
children aged
7-13 y and
their parents..
Rufi 1998
Treatment
Names
selected from
Finnish
Insurance
Register
IV
IV
Cross sectional
Questionnaire
IV
IV
IV
IV
Questionnaire
Cross sectional
survey
Questionnaire
Retrospective
medical record
audit plus
telephone
interview
multicentre
study
273
37 and 38
39
Johnston
1992 and
1990
Morris
1997
89 patients,
who attended
a teaching
Mean age
11.9yrs
DARTS/
MEMO
Collaboration
. (Diabetes
Audit and
Research in
Tayside
Scotland.
Medicines
Monitoring
Unit)
Mean age
12.8 yrs
140 children
with T1D and
their mothers.
Mean
duration of
T1D = 5.5
years.
Joslin Clinic,
Boston
consecutive
patients (aged
13-18 yr)
with insulindependent
diabetes
mellitus
recruited
during their
regular
quarterly visit
to a diabetes
clinic in a
large urban
hospital.
57 children
The prescribed
insulin dose and
volume of
insulin
prescriptions
supplied were
used to
calculate days
of maximum
possible insulin
coverage per
annum,
expressed as the
adherence
index.
Interviews 3
times over 2
week period
Associations between glycaemic
control (HbA1c), episodes of diabetic
ketoacidosis, and all hospital
admissions for acute complications
and the adherence index were
modelled.
Effects of age and duration on
metabolic control and adherence.
Psychological predictors of
compliance
Self-Esteem Scale, the Children's
Depression Inventory, an assessment
of the frequency of binging in the past
3 mo, and parallel forms of an
adherence scale and a self-efficacy
scale that were developed for use in
this study.
36
Jacobson
1987
1992
Direct
evidence of
poor
compliance
with insulin
therapy in
young
patients with
IDDM
There was a significant inverse association between
HbA1c and the adherence index (R2 = 0.39; p < 0.001).
Study demonstrated direct evidence of poor compliance
Adherence index was inversely related to hospital
admissions for diabetic ketoacidosis (p < 0.001) and all
hospital admissions related to acute diabetes
complications (p = 0.008).
All patients
<30years
attending
clinic were
studied.
Assesses at
baseline and
1.6 years later
18 month
follow up
adherence in
adolescents
with insulindependent
diabetes
mellitus is
associated
with
behavioural
and
psychological
variables
Insulin was prescribed at 48IU/day and mean insulin
collected from pharmacies was 58IU/day. However,
25 (28%) of the 89 patients obtained less insulin than their
prescribed dose (mean deficit 115 (68; range 9-246]
insulin days/annum)
Older patients were less adherent and had worse HbA1c
Patients with higher self reported self esteem, and parent
reported confidence, adjustment and social functioning
were more adherent
Adolescents (13-15yrs) less compliant than children (912yrs).
There was no sex difference in reported binging, but, as
expected, adolescent females reported less adherence
overall (F[7,184] = 2.5, P = 0.018).
Together, the psychological variables accounted for 50%
of the variance in adherence.
lower self-esteem (r = 0.45, P less than 0.001) and selfefficacy (r = 0.57, P less than 0.001), more depressive
symptoms (r = -0.50, P less than 0.001), more binging (r =
-0.36, P less than 0.001), and had higher HbA1c (r = 0.24, P less than 0.001) than those with higher adherence
scores.
Comparative
study
Longitudinal
Longitudinal
III-3
IV
IV
274
45
Goldston
1997
91
adolescents
attending
diabetes
outpatient
clinic
appointments
IDDM self-care
autonomy was
assessed using
two wellvalidated
measures. Three
measures of
psychological
maturity
(cognitive
function, socialcognitive
development,
and academic
achievement)
were also
collected for
each child.
Semistructured
and structured
interview
instruments and
self-report
questionnaires
were used to
determine
history of
suicidal
thoughts and
behaviour,
serious noncompliance
with the
Between-group differences in
treatment adherence, diabetes
knowledge, glycaemic control, and
hospitalization rates were explored.
Based on these scores, participants
were categorized as exhibiting
constrained, appropriate , or excessive
self-care autonomy.
Composite indexes of self-care
autonomy / psychological maturity
were formed, and the ratio of the selfcare autonomy index to the
psychological maturity index
quantified each child's deviation from
developmentally appropriate IDDM
self-care autonomy.
43
Wysocki
1996
hospital
paediatric or
young-adult
diabetes
clinic in 1993
and 1994.
(mean age 16
(SD 7) years,
diabetes
duration 8 (4)
years, and
glycosylated
haemoglobin
(HbA1c) 8.4
(1.9)%)
100 T1D
youths
Diagnosable psychiatric disorder and not living in a twoparent home were related to non-compliance with medical
treatment.
Duration of IDDM and psychiatric diagnosis were related
to both suicidal ideation within the previous year and
lifetime suicidal ideation.
The rate of suicidal ideation among the diabetic
adolescents was higher than expected, but the rate of
suicide attempts was comparable with that reported for the
general population. Suicidal thoughts were strongly
associated with serious non-compliance with the medical
regimen.
Excessive self-care autonomy increased with age and was
less common among intact two-parent families but was
unrelated to other demographic factors.
Controlling for age revealed that the excessive self-care
autonomy group demonstrated less favourable treatment
adherence, diabetes knowledge, hospitalization rates, and,
marginally, glycaemic control.
with insulin therapy.
Diagnosable
psychiatric
disorder and
not living in a
two-parent
home were
related to
noncompliance
with medical
treatment.
Scottish study
Semistructured
and structured
interview
instruments and
self-report
questionnaires
cross-sectional
study
IV
IV
275
47
48
Peveler
1992
Rydall
1997
mean age
15+/-2 years
91 young
women with
IDDM
Studied at base
line and 5 yrs
later
Prevalence and persistence of
disordered eating behaviour (on the
basis of self-reported eating and
weight-loss practices, including the
intentional omission or underdosing
of insulin to control weight) and the
Of the 65 women with normal eating behaviour at base
Eating disorder features and insulin misuse for shape and
weight control were not found in IDDM or non-diabetic
boys, and these two groups did not differ in their body
weight.
At base line, 26 of 91 young women (29 percent) had
highly or moderately disordered eating behaviour, which
persisted in 16 (18 percent) and improved in 10 (11
percent).
Fifteen percent had omitted or reduced their dose of
insulin to influence their shape and weight.
Nine percent of the IDDM girls met diagnostic criteria for
an operational version of 'Eating disorder not otherwise
specified.'
However, clinical eating disorders were no more common
among adolescent girls with IDDM than among nondiabetic control subjects.
Mean HbA1c in eating disorder group was significantly
higher than those without eating disorders (10% compared
with 8.9%, p<0.02))
Adolescent girls with IDDM were heavier than nondiabetic female control subjects and were dieting more
intensively to control their shape and weight.
Mean
duration of
T1D 6.4years
A crosssectional
survey of
eating habits
and attitudes
conducted in
76
adolescents
with IDDM,
and age- and
sex-matched
non-diabetic
control
subjects
Assessed by standardized research
interview adapted for use with
patients with diabetes (EDE).
Glycaemic control was assessed by
GHb assay
Those with eating disorders were less likely to follow
food plan or perform blood glucose monitoring.
Mean age
15.1 years
Incidence of bulimia nervosa 12%
Incidence of anorexia nervosa 1%
12% reported intentional insulin under treatment as a
method of weight control
Mean age of eating disorder patients 16.2 years.
Questionnaire
HbA1c level
Clinical information from hospital
notes
Toronto,
Canada
103 Female
T1D patients
attending
diabetes
clinic.
46
Rodin
1991
medical
regimen, current
psychiatric
disorder,
hopelessness,
and selfefficacy
expectations.
N/A
High
incidence of
intentional
insulin
omission to
control
High
incidence of
insulin
omission in
girls.
Case series
cross-sectional
survey
Survey
questionnaire
and medical
note review
IV
IV
IV
276
association of such eating disorders
with metabolic control, diabetic
retinopathy, and urinary albumin
excretion.
Disordered eating at base line was associated with
retinopathy four years later (P=0.004), when 86 percent of
the young women with highly disordered eating
behaviour, 43 percent of those with moderately disordered
eating behaviour, and 24 percent of those with
nondisordered eating behaviour had retinopathy.
At base line, the mean (+/-SD) haemoglobin A(1c) value
was higher in the group with highly disordered eating
behaviour (11.1+/-1.2 percent) than in the groups whose
eating behaviour was moderately disordered (8.9+/-1.7
percent) or nondisordered (8.7+/-1.6 percent, P<0.001).
Omission or underdosing of insulin lose weight was
reported by 12 of 88 young women (14 percent) at base
line and 30 (34 percent) at follow-up (P=0.003).
line (71 percent), 14 (15 percent) had disordered eating at
follow-up.
weight
Literature
reviewed until
June 1999
Compared behavioural
intervention (education or skills
training) with control group.
Emotional/psychological
interventions (18%)
Dietary interventions (19%)
Metabolic measures
Skills training (39% studies)
Age range 9-21
years.
Most studies from
USA (67.7%)
Outcome
Psychosocial
Self or parent reports of
changes in psychological
or interpersonal constructs
(e.g. self-efficacy;
diabetes-specific stress)
Intervention
Question asked “Do
educational and psychosocial
interventions for adolescents
with type 1 diabetes have
beneficial effects on biological
and psychosocial outcomes?”
Population
Systematic review
of 62 studies from
Health
Technology
Assessment
Program UK.
Ref No
52
These studies demonstrate the
variety of intervention and
outcomes that have been
studied. All the pre-, post
was 0.33 (95% CI 0.04 – 0.70)
for glycated haemoglobin with
outliers; significant
heterogeneity (0.08 without 2
outliers)
for psychosocial outcomes was
0.37 (95% CI 0.19-0.55
Results
Small to medium effect on
HbA1c and psychosocial
outcome of educational and
psychosocial intervention.
Identifies need for future
intervention trials
The meta-analysis of the
RCT’S should be treated with
caution due to the variation in
studies and intervention
62 studies in total.
25 RCTs reviewed (16 with
sufficient detail to enable effect
sizes to be calculated).
37 other study designs eg non
RCT’s without control groups,
pre and post intervention
studies
Comments
Rigorous search strategy with
appropriate inclusion criteria.
The effect of psychosocial interventions on metabolic and psychological outcomes in children and adolescents with type 1 diabetes.
Study
Hampson
2001
13.2
and the
duration of
diabetes was
7+/-4 years.
Design
Systematic
review
Level
I
277
55
Laffel
2003
Haemoglobin A1c was
measured at each visit.
Patients in both study groups
were seen at 3- to 4-month
intervals and were followed
prospectively for 1 year.
Of 128 eligible
families attending
Joslin clinic
(USA) 105 agreed
to participate.
Patients of
families not
particiapating
were slightly older
but otherwise not
Both groups had similar
frequencies of blood
glucose monitoring (BGM)
and insulin dosing.
Measures of family
involvement in diabetes
tasks, DFC, and quality of
life were performed at
baseline and after 1 year.
Family relationships,
psychological adjustment
to diabetes, treatment
adherence and diabetic
control were assessed at
baseline, after 6 and 12
months treatment
Randomised to a familyfocused teamwork (TW)
intervention or to standard
multidisciplinary diabetes care
(SC).
Interested families who met the
inclusion criteria (n=178)
completed two screening
questionnaires; of 132 families
exceeding the cutoff score, 119
(90%) enrolled in the study
Families paid $100 to promote
adherence and for completing
questionnaire.
Randomized 119 families of
adolescents with diabetes to 3
months' treatment with either
BFST, an education and
support Group (ES), or current
therapy (CT).
105 children and
adolescents, 8 to
17 years of age,
with T1DM for <
or =6 years.
Aged 14.3 +/-1.3
yrs, diabetes
duration 5.2 +/-3.7
years. 51 males,
68 females.
RCT Of
Behavioural
Family Systems
Therapy (BFST)
For Families Of
Adolescents With
Diabetes
53
Wysocki
2001
In multivariate analysis, TW
intervention and the daily
frequency of BGM
significantly predicted HbA1c
(R (2) = 0.17, P =.05).
Families exposed to the TW
intervention maintained or
increased family involvement
significantly more than families
exposed to SC (P =.05).
BFST yielded some
improvement in parentadolescent relationship. Factors
mediating the effectiveness of
BFST need to be clarified.
After 1 year, A1c was 8.2% +/1.1% in TW compared with
8.7% +/- 1.5% in SC (P <.05).
There were no effects on
treatment adherence.
No significant differences on
HbA1c between groups were
noted.
Compared with CT and ES,
BFST yielded lasting
improvement in parentadolescent relations and
reduced diabetes-specific
conflict (p<0.05).
At 12 months BFST effects on
psychological adjustment to
diabetes differed from CT
group (p,<0.05) but not from
the ES group.
Other studies published after the Hampson 2001 Health Technology Appraisal Systematic Review
design studies reported some
benefit - however because of
the low level of study design
and small numbers these
benefits should be treated as
provisional until more rigorous
results are available
After enrolment, two further
patients were excluded (I
because of severe eating
disorder; 1 because of
Three families (2.8%)
discontinued study
participation because of
insurance-related transfer of
care; these were excluded from
analyses
All scheduled intervention
sessions were completed by
87% of BFST families and 91%
of ES families
Randomisation:
stated
Losses to follow-up/response
rates:
Post-treatment evaluations
were completed by 87% of
BFST families and 12-month
follow-up by 108 families
(91%)
Randomisation:
stated.
Despite careful randomisation,
the three groups differed at
baseline along many
meaningful dimensions. The
BFST group included
significantly fewer intact
families and more single-parent
families.
RCT
RCT
II
II
278
105 patients who
met selection
criteria attending
Yale Diabetes
clinic were
invited to
participate and 77
agreed. Those
who refused were
not significantly
different in age,
gender, ethnicity.
Seventy-seven
patients (43
females, 95%
white) 12 to 20
years (mean =
14.2 +/- 1.9;
duration, 8.7 +/3.9)
77 patients electing to initiate
intensive diabetes management
(IDM) were randomly assigned
to one of two groups: with or
without coping skills training
(CST), which consists of 6
small group sessions and
monthly follow-up to help
youth cope with their lives in
the context of diabetes
management; skills included
social problem solving,
cognitive behaviour
modification, and conflict
resolution.
Clinical data (glycosylated
haemoglobin level, height,
weight, adverse effects)
were collected monthly.
Data were collected before
the intervention and at 3, 6,
and 12 months after the
intervention by using the
Self-Efficacy for Diabetes
Scale, Children's
Depression Inventory,
Issues in Coping with
IDDM, and the Diabetes
Quality of Life: Youth
scales.
Losses to follow-up/attendance:
Attendance at sessions was
98%
All CST groups were
audiotaped and reviewed to
ensure coping skills were
taught consistently across the
groups
Conclusion: The addition of
behavioural intervention to
IDM in adolescence results in
improved metabolic control and
quality of life over 1 year
Blinding:
Diabetes care providers and
research assistants collecting
data were blinded to study
group of participants
The CST and IDM groups were
comparable at baseline.
Randomisation:
stated
Final sample incuded 100
famiies (50 in each group)
diagnosis of a learning
disorder)
In males, CST did not affect
adverse outcomes of IDM
hypoglycaemia, diabetic
ketoacidosis, and weight gain,
but CST decreased the
incidence of weight gain (P
=.05) and hypoglycaemia in
females (P =.03).
Successful family involvement
may assist in the preservation
of health and the prevention of
long-term diabetes
complications for youth with
diabetes.
CST subjects had lower
glycosylated haemoglobin (P
=.001) and better diabetes (P
=.002) and medical (P =. 04)
self-efficacy, and less impact of
diabetes on their quality of life
(P =.005) than youth receiving
IDM alone after 1 year.
Ambulatory TW intervention
prevented the expected
deterioration in glycaemic
control seen with SC in youths
with T1DM of < or =6 years'
duration.
Despite increased family
involvement, the TW group
reported no increase in
Diabetes Related Family
Conflict or decrease in quality
of life.
59
Ref No
13.3
Grey 2000
At entry, HbA1c
was 8.4% +/1.3% in TW and
8.3% +/- 1.0% in
SC.
Patients (n = 100)
completed followup, (50 in TW and
50 in SC).
significantly
different.
RCT
II
279
Mean follow up
7.4 years (for
adolescents)
OR
125 adolescents
with no
retinopathy and 70
with mild
retinopathy
Intervention
Population
Adolescent
subgroup of
DCCT trial. Age
13-17 years
Ref No
2
Outcome
complications
Nephropathy:
10%
reduction
in
–70% to 52%; p=0.745 in those
55% (95% CI 3% to 9%);
retinopathy
Results
Retinopathy:
25-88%, p=0.010) (in those
Effect of intensive diabetes management on microvascular and macrovascular complications in adolescents.
Study
DCCT 1994
14.1
withdrew;
some time
>95%
of
scheduled
treatment was 95%;
Blinding:
regimens;
Comments
Landmark study.
Design
RCT
Medforum, 2000
35
60
61
1
Level
II
280
63
DCCT 1993
1441 patients with
T1D aged 13-39
years.
726 with no
retinopathy at
baseline (primary
intervention
group) and 715
with mild
Patients with
recognised risk
factors (other than
diabetes) were
excluded from the
trial
1441 patients with
T1D
726 with no
retinopathy at
baseline and 715
with mild
retinopathy
OR
prevention)
once daily monitoring
OR
BG monitoring
20
DCCT 1995
complications
macrovascular
complications
by 76% (95% CI 62-85) in
(p<0.001); combined 63%
(95% CI 52-71), p0.002.
The reduction in some, but not
all, cardiovascular risk factors
suggests a potential beneficial
effect of intensive therapy on
macrovascular disease in
insulin-dependent diabetes
mellitus
Mean total serum cholesterol,
LDL, cholesterol, and
triglycerides were significantly
reduced in intensive-tx gp (p <
or = 0.01), as was the
development of LDL
cholesterol levels > 160 mg/dl.
There were no differences in
the cumulative incidence of
hypertension.
Differences were not
statistically sig (p = 0.08).
No. of major macrovascular
events was twice as high in
conventional tx gp (40 events)
as in intensive-treatment group
(23 events).
Adherence:
49 patients deviated from
intensive to conventional
therapy for some period of the
study; 104 deviated form
conventional to intensive
therapy (95 of these were
pregnant women);
Overall intensively-treated
patients spent >98% of their
time on the assigned treatment,
and conventionally-treated
patients spent 97% of their
tiome on that therapy
Landmark study.
committee)
11 patients died during the
study and 8 dropped out. At the
end of the study all 8 were
determined to be alive and
healthy, with no history of
major macrovascular events;
>95% of scheduled outcome
date were obtained
Analysis:
All analyses carried out on an
intention-to-treat basis
Blinding:
Morbidity and Mortlaity
Committee classified deaths
and cardiovascular events
without knowledge of treatment
assignment, according to preestablished criteria
RCT
RCT
II
II
281
95
Of 1441 patients
who participated
in the DCCT,
1229 patients
participated in
EDIC
(Epidemiology of
Diabetes
Interventions and
Complications)
N = 611
Four year follow up from close
of DCCT
(DCCT = Intensive insulin
therapy with frequent BG
monitoring
OR
once daily monitoring)
prevention)
Nathan 2003
retinopathy
(secondary
intervention
group)
B-mode ultrasound of the
internal and common
carotid arteries to measure
intimal thickness (in 19941996 and 1998-2000)
Adverse events:
Mean progression of the
intima-media thickness sig. less
in group that received intensive
therapy during DCCT than in
group
that
received
conventional
therapy
(progression of the intimamedia thickness of the common
carotid artery, 0.032 vs. 0.046
mm; P=0.01; and progression
of the combined intima-media
Nephropathy:
(95% CI 21-52) and
19-74);
(p=0.001)
57% (95% CI 29-73); p0.002
(95% CI 38-74), p0.002
Blinding:
Assessment of intima-media
thickness carried out by a
single operator who was
blinded to patientt’s treatment
assignments
As for DCCT
Compliance:
study;
11 patients died;
would be hazardous
regimens
Blinding:
tool
RCT
II
282
thickness of the common and
internal carotid arteries, -0.155
vs. 0.007; P=0.02)
International Society for Pediatric and Adolescent Diabetes: Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Zeist, Netherlands, Medforum, 2000
National Health and Medical Research Council: Screening for Diabetic Retinopathy. In Clinical Practice Guidelines for the Management of Diabetic Retinopathy. Canberra, Australian Government
Publishing Service, 1997, p. 23-33
American Diabetes Association: Management of Dyslipidemia in Children and Adolescents With Diabetes. Diabetes Care 26:2194-2197, 2003
Studies were included if they specifically addressed the frequency of screening for coeliac disease in children and adolescents with type 1 diabetes. While many studies
described the prevalence of autoantibodies in children and adolescents with type 1 diabetes, we did not find any relevant studies that specifically addressed the frequency of
How frequently should children and adolescents with Type 1 diabetes be screened for coeliac disease?
Studies were included if they specifically addressed the frequency of screening for thyroid disease in children and adolescents with type 1 diabetes. While many studies
described the prevalence of autoantibodies in children and adolescents with type 1 diabetes, we did not find any relevant studies that specifically addressed the frequency of
screening. In the absence of other evidence the current consensus guidelines form the basis for the screening recommendations. Articles describing prevalence of thyroid
disease in children with type 1 diabetes are mentioned in the text.
How frequently should children and adolescents with type 1 diabetes be screened for thyroid disease?
110
111
122
Ref No
21
42
14.2
Studies were included if they specifically addressed the frequency of screening for macrovascular disease in children and adolescents with type 1 diabetes. While some
studies described the prevalence of macrovascular complications in children and adolescents with type 1 diabetes, we did not find any relevant studies that specifically
addressed the frequency of screening. In the absence of other evidence the current consensus guidelines form the basis for the screening recommendations. Articles relating to
macrovascular disease in children and adolescents with type 1 diabetes are mentioned in the text.
How frequently should children and adolescents with type 1 diabetes be screened for macrovascular complications?
Studies were included if they specifically addressed the frequency of screening for microvascular disease in children and adolescents with type 1 diabetes. While some studies
described the prevalence of microvascular complications in children and adolescents with type 1 diabetes, we did not find any relevant studies that specifically addressed the
frequency of screening. In the absence of other evidence the current consensus guidelines form the basis for the screening recommendations. Articles describing prevalence of
microvascular complications in children with type 1 diabetes are mentioned in the text.
How frequently should children and adolescents with type 1 diabetes be screened for microvascular (retinopathy, nephropathy, neuropathy) complications?
conventional and
n = 618 intensive
therapy.
283
Effect of a gluten free diet (GFD) in asymptomatic patients with type 1 diabetes found to have coeliac disease on routine screening.
63
Acerini 1998
8 with diagnosed
coeliac disease
167 children &
adolescents with
TID screened with
EMA and IgA (+/AGA).
Population
18 patients
detected out of
776 children with
T1D by
retrospectively
screening stored
serum samples.
Screened by antireticulin and antigliadin antibodies.
Confirmed
diagnosis by
jejunal biopsy.
Children and
adolescents (mean
age 11.4) with
type1 diabetes.
Gluten free diet (GFD)
Intervention
Exclusive GFD
Ref No
57
Study
Saukkonen
2002
Antibody status,
symptoms, BMI SDS,
HbA1c ,
Repeat small bowel
biopsies
Weight
Height
HbA1c
Outcome
HbA1c reduction with gluten
All had normal antibody tests
after 3-6 months of GFD
Asymptomatic patients
reported no change in
wellbeing on the GFD,
although trend for BMI SDS to
increase was not significant
(p=0.248)
Height did not change before or
after dx.
Weight for height did not
change before diagnosis, but
there was a significant increase
after dx and intro of GFD
(p=0.02)
Eleven (6.6%) antibody
positive ,9 had biopsies: 8
coeliac (1 'classical'; 1 anaemia;
3 'atypical'; 3 asymptomatic).
GFD did not affect glycaemic
control HbA1c
Only one patient reported
symptoms at the time of
diagnosis. 2 patients had iron
deficiency anaemia.
However on retrospective
questioning 9 reported GI
symptoms (mostly flatulence,
which resolved in all but 2
patients.
Results
Prevalence 2.4% of type 1
diabetics.
UK study.
Clinic population at john
Radcliff Hospital, Oxford.
Serological screening is
effective, although the
therapeutic benefit of dietary
therapy in asymptomatic cases
remains uncertain
One patient died, cause of
death not stated.
Short follow up period. Details
up to one year post diagnosis of
coeliac disease only.
Comments
Nationwide screening
programme for Childhood
Diabetes in Finland ( DiMe)
study.
Overt GI symptoms reported in
1 patient before disclosure of
diagnosis.
Articles chosen if they addressed the question of GFD in truly asymptomatic children and adolescents with type 1 diabetes detected on routine screening.
15.1
Case series
longitudinal
follow-up
Design
Retrospective
case series
IV
Level
IV
screening. In the absence of other evidence the current consensus guidelines form the basis for the screening recommendations. Articles describing the prevalence of coeliac
disease in children with type 1 diabetes are mentioned in the text.
284
Medforum, 2000
NSW Health Department: Principles of Care and Consensus Guidelines for the Management of Diabetes Mellitus in Children and Adolescents. 1998
Population
67 diabetic
children and a
comparison group
matched for age,
sex, and social
class.
N/A
Intervention
Outcome
Questionnaire, clinical examination,
and biomechanical assessment for
foot pathology (limited joint mobility,
plantar callus, skin conditions) contact
with podiatry services and knowledge
Ref No
1
The effect of type 1 diabetes on joint mobility in the feet of young people.
Study
Barnett 1995
16.1
Among the diabetic group there was
ignorance and misconceptions, and
previous contact with a podiatrist was
minimal.
42 children with diabetes had received
foot health education compared with 27
in the comparison group.
Increased incidence of abnormal skin
conditions (53 children with diabetes, 27
comparison group).
Increased biomechanical anomalies
(limited joint mobility) (58 children with
diabetes, 34 comparison group);
Results
Increased foot pathology (limited joint
mobility, plantar callus) in the children
with diabetes (52 children) compared
with comparison group (28 children);
Comments
Design
Comparative
study
Level
IV
Studies were included if they specifically addressed the frequency of screening for foot complications in children and adolescents with type 1 diabetes. While many studies
described the prevalence we did not find any relevant studies that specifically addressed the frequency of screening. In the absence of other evidence the current consensus
guidelines form the basis for the screening recommendations.
How frequently should children and adolescents with Type 1 diabetes be screened for foot complications?
46
59
60
74
Ref No
45
15.2
free diet was not significant
(p=0.697)
285
N/A
Limited joint mobility was defined as
less than the fifth percent reference
for controls
Also screened for diabetes
complications (retinopathy and
nephropathy)
Hands, feet and hips were examined.
Foot length, arch length, joint
mobility, peak pressure and pressure
time integrals were evaluated
Thickness of the skin on the plantar
surface of the foot and plantar
aponeurosis were examined using
ultrasound.
Ref No
Population
Intervention
Study
302 diabetic
adolescents and
51 non-diabetic
controls (aged
11.5-20 years).
216 young people
with Type 1
diabetes mellitus
and 57 controls
Outcome
Results
Diabetic adolescents showing LJM in
any of these areas, except the prayer
sign, were more likely to have
retinopathy (odds ratio 2.53, CI: 1.534.18). Those with LJM in the foot were
more likely to have albumin excretion
rates >7.5 microg/min (OR 2.06, CI:
1.16-3.68).
Limited active IP joint extension, a
positive 'prayer sign', occurred in 35%
of diabetic adolescents and 14% of
controls.
13% of diabetics had limited passive
extension of the interphalangeal (IP)
joints of the hands compared to 0% in
controls.
fifth metacarpophalangeal (MCP) joint
in 26%
first metatarsophalangeal (MTP) joint in
18%
subtalar (ST) joint in 35%,
Males were nearly 3 times more likely
to have thickened plantar aponeurosis.
Reduced motion was found in diabetic
adolescents at the:
Thickened plantar aponeurosis was
associated with foot size, male gender
and subtalar joint limited joint mobility
(P < 0.01).
The plantar aponeurosis was
significantly thicker in the diabetic
subjects than controls.
Skin was not significantly thicker in the
diabetic subjects.
The management of high plantar pressure and callus in adolescents with type 1 diabetes.
19
Duffin 1999
16.2
14
Duffin 2002
Comments
Clinic population.
Referred for diabetes
complications
screening. Any
patients with known
joint condition or
arthritis was excluded
Any patients with
known joint condition
or arthritis was
excluded
Design
Comparative
study
Level
IV
IV
286
17 diabetic
subjects with high
peak plantar
pressure and
17 diabetic
subjects with
plantar callus
211 adolescents
with diabetes and
57 non-diabetic
controls
Treatment with foot
orthosis, cushioning
or combination of
both
Peak plantar pressure 12 months after
intervention
Combination of cushioning and orthosis:
significant decrease (p<0.001)
Orthosis alone: significant decrease in
peak plantar pressure (p=0.05)
Cushioning alone: significant decrease
in peak plantar pressure (p=0.001)
Clinic population.
Referred for diabetes
complications
screening. Any
patients with known
joint condition or
arthritis was excluded
3
Case series
study with
interventional
phase (pre-test,
post test).
IV
Population
64 children and
adolescents (8-15
years of age) with
diabetes treated
and monitored
according to a
standard medical
protocol and
receiving
extensive
preventive oral
health care based
on individual
needs.
N/A
Intervention
Results
Patients with less good metabolic
control (>8.0% Hb A(Ic)) had higher
glucose levels in resting saliva (p <
0.05)
Patients with less good metabolic
control (>8.0% Hb A(Ic)) had
significantly higher caries incidence (p <
0.05) compared to those with good
metabolic control.
The most influential determinants for
high caries development during the 3year follow-up period were metabolic
control (odds ratio, OR = 5.7), poor oral
hygiene (OR = 6.5), previous caries
Outcome
Data on blood glucose and
glycosylated haemoglobin (Hb A(Ic))
were collected from the medical
records.
Whole saliva was collected every 3rd
month and secretion rate, buffer
capacity, glucose concentration,
mutans streptococci and lactobacilli
counts were determined.
Dental examinations, including
radiographs, were carried out once a
year.
Ref No
4
The effect of type 1 diabetes on dental health in children and adolescents.
Study
Twetman
2002
17.1
Comments
Design
Observational
case series and
retrospective
medical note
survey
Level
IV
Studies were included if they specifically addressed the frequency of screening for dental complications in children and adolescents with type 1 diabetes. While many studies
described the prevalence we did not find any relevant studies that specifically addressed the frequency of screening. In the absence of other evidence the current consensus
guidelines form the basis for the screening recommendations.
How frequently should children and adolescents with Type 1 diabetes have a dental review?
Ref No
20
16.3
Duffin 2003
287
7
8
9
Pinson 1995
Marin 2002
Takahashi
2001
Thirty-nine
periodontally
Twenty diabetic
patients with good
metabolic control,
twenty diabetic
patients with poor
metabolic control
and forty healthy
subjects
117 Japanese
T1DM subjects
(53 male, 64
female, mean age
+/- SD, 16 +/- 6.5
years)
26 type I diabetic
patients and 24
control subjects
(average age
13.4years)
Thirty juvenile
diabetics and 30
healthy
individuals
N/A
N/A
Glycosylated haemoglobin (GHb) to
obtain a measure of diabetic control.
N/A
Microbiological tests for four
periodontal pathogens,
Porphyromonas gingivalis,
Actinobacillus
actinomycetemcomitans, Prevotella
intermedia and Capnocytophaga
Clinical examination for signs of
periodontitis, gingivitis.
Periodontal markers: Plaque, gingival,
mobility, probing depth, attachment
level, bleeding on probing, and
marginal bone loss.
Glycosylated haemoglobin
Clinical periodontal details: plaque
index, gingival fluid flow, gingival
index, probing depths, clinical
attachment levels, recession, and
bleeding on probing
Evaluated for dental caries and oral
mucosal lesions, with the performance
of basal and stimulated sialometry,
periodontal variables such as the
presence of bacterial plaque, gingival
status and attachment losses
N/A
6
MirallesJorda 2002
In the T1DM subjects, the Periodontitis
group had a significantly longer mean
duration of diabetes and a higher
percentages of subjects harbouring P.
gingivalis and P. intermedia than the
T1DM subjects : 12 had periodontitis,
32 had gingivitis and 73 were
periodontally healthy
There was no significant association
between the level of control of diabetes
(GHb) and clinical variables. However,
comparisons based on site-specific
measurements showed the gingival
index to be somewhat higher among the
diabetics (p = 0.0002), and examination
of interaction effect plots showed the
diabetic group to have higher average
gingival index for most teeth and higher
or the same plaque index levels on all
teeth relative to controls.
Poor glycaemic control associated with
periodontal disease (p<0.05)
The diabetic group had better oral
hygiene habits.
No statistically significant differences in
the overall means for the 2 groups for
average attachment loss, probing depths,
recession, gingival index, plaque index,
gingival fluid flow, or bleeding on
probing.
No difference between groups for
salivary flow, dental caries or mucosal
lesions.
experience (OR = 5.3) and high levels of
salivary lactobacilli (OR = 5.0).
Diabetics had significantly more
periodontal attachment loss than non
diabetics.
Observational
case series
Observational
case series
Observational
case series
Observational
case series
IV
IV
IV
IV
288
Serum IgG antibody levels against P.
gingivalis were significantly elevated in
the Periodontitis group compared with
Gingivitis and Periodontally Healthy
groups.
Periodontally Healthy group.
Mean follow up
7.4 years (for
adolescents)
OR
125 adolescents
with no
retinopathy and 70
with mild
retinopathy
Intervention
Population
Adolescent
subgroup of
DCCT trial. Age
13-17 years
Ref No
2
HbA1c
Episodes of
hypoglycaemia
Outcome
complications
Severe hypoglycaemia: RR
2.96 (95% CI 1.90-4.62)
Hypoglycaemia resulting in
coma or seizure: RR 2.93
(95%CI 1.75-4.90)
Overweight: RR 2.11 95% CI
Diabetic ketoacidosis: RR 0.2
(95% CI 0..32-1.23)
Nephropathy:
10%
reduction
in
–70% to 52%; p=0.745 in those
55% (95% CI 3% to 9%);
retinopathy
Results
Retinopathy:
25-88%, p=0.010) (in those
withdrew;
some time
Blinding:
regimens;
Comments
Landmark study.
Australasian Paediatric Endocrine Group: APEG Handbook on Childhood and Adolescent Diabetes. Sydney, Australasian Paediatric Endocrine Group,
1996
Difficulties in glycaemic control in adolescents compared with adults.
Study
DCCT 1994
18.1
ochracea
Chapter 18: Adolescent Health Issues
Ref No
12
17.2
healthy, agematched
nondiabetics
controls.
Design
RCT
Level
II
289
3
1441 patients with
T1D aged 13-39
years.
726 with no
retinopathy at
baseline (primary
intervention
group) and 715
with mild
retinopathy
(secondary
intervention
group)
prevention)
OR
prevention)
DCCT 1993
complications
Nephropathy:
(95% CI 21-52) and
19-74);
(p=0.001)
57% (95% CI 29-73); p0.002
(95% CI 38-74), p0.002
by 76% (95% CI 62-85) in
(p<0.001); combined 63%
(95% CI 52-71), p0.002.
HbA1c (%+/-SE): 8.06+/-0.13
vs 9.76+/-0.12 (reduction of
1.7% +/-SE 0.18)
1.31-3.40)
Compliance:
study;
11 patients died;
would be hazardous
regimens
Blinding:
tool
Landmark study.
committee)
>95%
of
scheduled
treatment was 95%;
RCT
II
290
16
17
Eiser 1993
Kipps 2002
229 subjects
T1D
>18 and <
16 between
the years of
1985 and
1995
Oxford, UK
UK
69 T1D patients
164
interviewed
by a single
nurse
222 audit of
notes.
Patient
questionnaire
2 years pre transfer: 98%
Rate of clinical
attendance (at least 6
monthly)
p < 0.0005 2 years pre transfer vs. 2
years post
transfer
2 years post transfer: 61%,
2 years post transfer: 81%
1 year pre transfer: 87%
rated about 3.4 out of 5 (0=not
important, 5=very important)
17.9 years range (13.3 -22.4 years)
Importance of visits before transfer
Mean age of transfer
27.3% offered reason
44.8% any age up to 25 yrs
15.9 yrs
48.6% between ages of 17 & 20 yrs
5.7% before age of 17 yrs
Pt knowledge of transfer reasons
Best age of transfer
1.9% Don’t
care
1.9% Don’t know
14.3% GP only
Results
72.3% Public hospital
Age (15-18)
Outcome
Preferred source of further adult care
42.9% Private specialist
Intervention
Patient
questionnaire
Australia
Population
105 T1D patients
Ref No
15
Current transition processes and outcomes for adolescents with type 1 diabetes moving to the adult care system.
Study
Court 1993
18.2
Adverse events:
Comments
105 responses out of
152 questionnaires
sent
Survey
Survey
Design
Survey
IV
IV
Level
IV
291
18
Canada
Two different
hospitals.
212 subjects
with type 1
diabetes
Transfer between
Oct 1990 and
Oct 1995.
Patient
Questionnaire
9.9 ± 1.9 vs. 11.4 ± 1.9%, p = 0.0004
57% satisfied
20% not sat.
24% indifferent
10% very important
43% important
46% not important
1% discouraging
18.5 ± 0.1 years
18.8 ± 0.2 years
Mean HbA1c at 2 yrs
before tx comparing
patients at
clinic 2 yrs post tx .
Satisfaction with transfer
Patients perception of
importance of meeting
adult clinic staff prior to
transfer
(mean ± SEM)
Suggested age of transfer
(mean ± SEM)
Adult care services now used
Unrelated to transfer outcome
(attendance
clinic)
Age at transfer
54% endocrinologist
65% felt later transfer would be better.
30% diabetes clinic
39% felt transfer was at correct time.
21% felt should have had transfer earlier
79%
Attendance of first
appointment in new clinic
Pacaud 1996
86%
p < 0.0005 2 years pre transfer vs. 2
years post
transfer
2 years post transfer: 24%,
2 years post transfer: 45%
1 year pre transfer: 54%
2 years pre transfer: 77%
Transfer letter identified in
clinical record
Rate of clinical
attendance (3-4 monthly)
Survey
IV
292
20
Jefferson
2003
302 paediatricians
surveyed in UK
42 young
people with
T1D
Attending
adolescent
or transition
clinic
questionnaire
Patient
Questionnaire
Definitely; 11/42 (26%) have some idea;
7/42
(17%) don’t know; 24/42 (57%)
6/42 (14%)
don’t know; 35/42 (84%)
6/42 (14%)
don’t know; 33/42 (79%)
2/42 (5%)
don’t know; 40/42 (95%)
Yes, more than once; 8/42 (19%) Yes,
once; 3/42
(7%) no; 23/42 (55%)not sure 8/42
(19%)
Yes, more than once; 4/42 (9.5%) Yes,
once; 4/42
(9.5%) no; 23/42 (55%) not sure 11/42
(26%)
14% at 14-16 yrs
31% at 16 years
45% at 16-20 years
53% transfer young people into a young
Where will the adult clinic be held?
How often will appointments be?
Which doctor will you see?
Which nurse will you see?
Have you met any of the
doctors at the adult clinic?
Have you met any of the
nurses at the adult clinic?
Age of transfer
3/42 (7%)
don’t know; 33/42 (79%)
When the adult clinic is held?
27.5%
(17% delay was more than 1 year)
A delay of more than 6
months bxn last visit
at paed. clinic and
first visit at adult clinic
Do you know :
19
Datta 2003
32.8% responded yes
Problem with
transition from paediatric
to adult care
13% no regular contact
3% family physician
Survey
Survey
IV
IV
293
21
Finland
1980-1983
61 cases of
adolescent T1D
followed one yr
before and 1 yr
after transfer
HbA1c measured at 3
monthly intervals
Diabetes clinics in
seven U.S. and
four European
cities,
Population
341 adults with
type 1 diabetes,
332 with type 2
diabetes, and 363
non-diabetic
spouse control
subjects.
N/A
Intervention
Ref No
22
Outcome
Driving mishaps
Mean HbA1c
The effect of type 1 diabetes on driving performance.
Study
Cox 2003
18.3
Salmi 1986
One-half of the T1D drivers
and three-quarters of the T2D
drivers had never discussed
hypoglycaemia and driving
with their physicians.
Crashes among T1D drivers
were associated with more
frequent episodes of
hypoglycaemic stupor while
driving, less frequent blood
glucose monitoring before
driving, and the use of insulin
injection therapy as compared
with pump therapy.
T2D drivers had driving
mishap rates similar to
nondiabetic spouses, and the
use of insulin or oral agents for
treatment had no effect on the
occurrence of driving mishaps.
Results
T1D drivers reported
significantly more crashes,
moving violations, episodes of
hypoglycaemic stupor, required
assistance, and mild
hypoglycaemia while driving as
compared with T2D drivers or
spouse control subjects (P <
0.01-0.001).
17.5 ± 0.5 years (range 16.5-18.8)
Comments
Type and severity of driving
mishaps not described
1 year after transfer: 9.9 ± 1.7 (n = 49)
p < 0.001
1st visit at the adult clinic 11.2 ± 2.3 (n
= 49)
adult
diabetes clinic
1 year before transfer: 11.2 ± 2.2 (n =
49)
Design
Questionnaire
Non
experimental
descriptive case
series
Level
IV
IV
294
23
37 adults with
type 1 diabetes
who drove a
simulator during
continuous
euglycaemia and
progressive
hypoglycaemia.
16 men, 21
women. Mean age
35.3+/-7.1 years .
Mean duration of
diabetes 17.5+/10.0 years.
Mean HbA1c
8.5+/-1.8%
N/A
During testing, driving
performance, EEG, and
corrective behaviours
(drinking a soda or
discontinuing driving)
were continually
monitored, and BG,
symptom perception, and
judgement concerning
impairment were assessed
every 5 min. Mean +/- SD
euglycaemia performance
was used to quantify z
scores for performance in 3
hypoglycaemic ranges
(4.0-3.4, 3.3-2.8, and <2.8
mmol/l).
Population
Patients with type
1 diabetes and
eating disorders
Intervention
N/A
Outcome
Data were extracted from the relevant casecontrol and follow-up studies
Ref No
47
Eating disorders in children and adolescents with type 1 diabetes.
Study
Nielsen 2002
18.4
Cox 2000
Bulimia Nervosa is increased (OR = 2.9) in T1D.
Comments
Recruited through
advertisements.
Simulated driving experience,
not real life
Results
Incidence of anorexia nervosa not significantly
increased in T1D.
High beta and low theta activity
and awareness of both
hypoglycaemia and the need to
treat low BG influenced
corrective behaviour.
Awareness of impaired driving
was associated with
neuroglycopaenic symptoms.
increased beta-wave activity,
and awareness of
hypoglycaemia.
Driving impairment was related
to increased neurogenic
symptoms and increased thetawave activity.
Corrective actions did not
occur until BG was <2.8
mmol/l (P<0.05).
Compared with euglycaemia
hypoglycaemic subjects
engaged in more driving across
the midline (P<0.01 for
BG<2.8 mmol/l), more
speeding (P<0.01 for BG 2.84.0 mmol/l and inappropriate
baraking (P<0.01 for BG 2.84.0 mmol/l)
During all three
hypoglycaemic BG ranges,
driving was significantly
impaired, and subjects were
aware of their impaired driving.
Design
Meta-analysis
of all relevant
case-control and
follow-up
studies
Case series
Level
IV
IV
295
49
NeumarkSztainer 2002
Source of data:
1. Diabetes
database and 2
previous
population based
studies
2. Danish
nationwide
psychiatric
admission case
register
70 adolescent
females and 73
adolescent males
with type 1
diabetes.
Mean age 15.3+/2.3 years (12-21
years)
Patients with type
1 diabetes and
eating disorders
(age range 0-29
years).
N/A
N/A
Data on BMI and glycosylated haemoglobin
(HbA1c) were drawn from medical records.
AHEAD (Assessing Health and Eating among
Adolescents with Diabetes) survey.
Indexes of mortality: crude mortality rate
(CMR) (a percentage), SMR, rate ratio (RR)
(mortality per 1,000 person-years of
observation), risk difference (RD), and survival
analysis.
48
Nielsen 2002
Family cohesion was negatively associated with
disordered eating among females (r = -0.52; P <
Higher levels of weight dissatisfaction tended to
be associated with unhealthy weight
control/disordered eating; associations with BMI
were inconsistent.
Weight control/disordered eating behaviours
were not associated with age, parental level of
education, family structure, or race/ethnicity.
Among the females, 10.3% reported skipping
insulin and 7.4% reported taking less insulin to
control their weight. Only one male reported
doing either of these behaviours.
Unhealthy weight control practices: in 37.9% of
the females and 15.9% of the males.
More females (92.4%) than males (53.6%)
reported weight control behavious to lose weight
or prevent weight gain (P<0.001).
Crude mortality rates were 2.5, 6.5, and 34.8%,
respectively.
Mortality rate was 2.2 (per 1,000 person-years)
for T1D, 7.3 for anorexia cases, and 34.6 for
concurrent cases.
With 10 years of follow-up, 13 of 510 females
with type 1 diabetes, 43 of 658 females with
anorexia nervosa, and 8 of 23 concurrent case
subjects had died.
Insulin misuse (IM) is increased when ED coexists with T1D (OR 12.6)
Anorexia nervosa has higher mortality than type
1 diabetes on all indexes of mortality.
Co-existing ED in T1D increases the overall
common OR for retinopathy to 4.8
ED-NOS and subthreshold ED was increased
(OR =2) in females with T1D.
246
adolescents
invited to
participate.
143 agreed
(58%)
Questionnaire
Population
register based
follow up study
IV
IV
296
51
52
Affenito
1997
Rydall 1997
mean age 15+/-2
years and the
duration of
diabetes was 7+/-4
years.
91 young women
with IDDM
Sweden
90 with T1D (1846 years of age)
Mean age 28.8
years
Recruited from
diabetes clinics
throughout
Connecticut and
Massachusetts
Adolescent males
with T1D
compared with
that of healthy
age-matched male
controls
Studied at
base line and
5 yrs later
N/A
Group differences in the degree of dietary
restraint, binge eating, and bulimic behaviours
anti weight, shape, and eating concerns were
assessed with the Eating Disorder Examination
(EDE) and the Bulimia Test Revised (BULITR).
Prevalence and persistence of disordered eating
behaviour (on the basis of self-reported eating
and weight-loss practices, including the
intentional omission or underdosing of insulin
to control weight) and the association of such
eating disorders with metabolic control,
diabetic retinopathy, and urinary albumin
excretion.
Categorized into one of 3 groups according to
the Diagnostic Statistical Manual of Mental
Disorders (DSM-III-R) criteria for eating
disorders: the clinical group (n = 14), the
subclinical group (partially fulfilling the
diagnostic criteria; n = 13), and the control
group (n = 63).
Eating Disorder Inventory for Children and an
interview.
50
Svensson
2003
Omission or underdosing of insulin lose weight
was reported by 12 of 88 young women (14
percent) at base line and 30 (34 percent) at
follow-up (P=0.003).
At base line, the mean (+/-SD) haemoglobin
A(1c) value was higher in the group with highly
disordered eating behaviour (11.1+/-1.2 percent)
than in the groups whose eating behaviour was
Of the 65 women with normal eating behaviour
at base line (71 percent), 14 (15 percent) had
disordered eating at follow-up.
The severity of bulimic behaviours, weight
concerns, reduced BMI, and decreased frequency
of blood glucose monitoring were associated
with elevated HBA(1c)
At base line, 26 of 91 young women (29 percent)
had highly or moderately disordered eating
behaviour, which persisted in 16 (18 percent) and
improved in 10 (11 percent).
Women with(p<0.05) subclinical and clinical
eating disorders had clinically elevated HbA(1c)
results. The Control HbA1c was 8.3+/-1.6.
subclinical group HbA1c 10+/-1.5% , clinical
group HbA1c 10.4+/-2.6% (p=0.05) and more
diabetes-related complications, compared with
the control subjects (Control group 0.6,
subclinical group 1.23, p=0.03, clinical group
1.23,p=0.03).
Male T1D patients had higher Drive for Thinness
scores (p=0.002)
Correlations between disordered eating and
HbA1c levels were significant among females (r
= 0.33; P < 0.01) and males (r = 0.26; P < 0.05).
Male patients were heavier than controls males (p
= 0.004)
0.001) and males (r = -0.41; P < 0.001), but
correlations with other measures of family
environment (control, independence, and
responsibility for diabetes management) were not
significant.
High
incidence of
intentional
insulin
omission to
control
weight
Diabetes
complications
by self-report
or chart
review.
Case series
Cohort study.
Questionnaire
Questionnaire
and interview
IV
IV
IV
297
Mean duration of
T1D 6.4years
Mean age 15.1
years
Toronto, Canada
103 Female T1D
patients attending
diabetes clinic.
A cross-sectional
survey of eating
habits and
attitudes
conducted in 76
adolescents with
IDDM, and ageand sex-matched
non-diabetic
control subjects
N/A
Questionnaire
HbA1c level
Clinical information from hospital notes
Assessed by standardized research interview
adapted for use with patients with diabetes
(EDE). Glycaemic control was assessed by
GHb assay
Mean HbA1c in eating disorder group was
significantly higher than those without eating
disorders (10% compared with 8.9%, p<0.02))
Those with eating disorders were less likely to
follow food plan or perform blood glucose
monitoring.
Mean age of eating disorder patients 16.2 years.
Incidence of bulimia nervosa 12%
Incidence of anorexia nervosa 1%
Eating disorder features and insulin misuse for
shape and weight control were not found in
IDDM or non-diabetic boys, and these two
groups did not differ in their body weight.
12% reported intentional insulin under treatment
as a method of weight control
Fifteen percent had omitted or reduced their dose
of insulin to influence their shape and weight.
Nine percent of the IDDM girls met diagnostic
criteria for an operational version of 'Eating
disorder not otherwise specified.'
However, clinical eating disorders were no more
common among adolescent girls with IDDM than
among non-diabetic control subjects.
55
Rodin 1991
18.5
54
Peveler 1992
Disordered eating at base line was associated
with retinopathy four years later (P=0.004), when
86 percent of the young women with highly
disordered eating behaviour, 43 percent of those
with moderately disordered eating behaviour, and
24 percent of those with nondisordered eating
behaviour had retinopathy.
Adolescent girls with IDDM were heavier than
non-diabetic female control subjects and were
dieting more intensively to control their shape
and weight.
moderately disordered (8.9+/-1.7 percent) or
nondisordered (8.7+/-1.6 percent, P<0.001).
High
incidence of
insulin
omission in
girls.
Survey
questionnaire
and medical
note review
Cross-sectional
survey
IV
IV
298
9
10
Davis 1996
Matyka 1999
29 prepubertal
T1D
12 children aged
12.4+/-2.6 years,
age (range 11.115.4 years),
duration of
diabetes 5.9+/- 3
years.
Population
24 school aged
children with T1D
(14 with hypo and
10 controls with
no hypo)
Controls were children with
T1D who did not have mild
hypo episode
Hyperglycaemia or
euglycaemia (Effect of
hyperglycaemia using a
modified glucose clamp to
maintain BG between 5-10
mmol/l or between 20-30
mmol/l)
Intervention
14 tested immediately after
complete symptom resolution
of mild hypo episode
Ref No
5
Cognitive function
WISC-111 subtests
Outcome
Neuropsych testing
The effects of type 1 diabetes on cognitive function in children and adolescents.
Study
Puczynski
1990
19.1
No sig diff. bxn noct hypo
nights and control nights
Analysis of variance
demonstrated as significant
decrease in performance IQ
when hyperglycaemic (106+/4.3 vs 112+/-4.5 IQ points,
p<0.05)
8/12 had decreased IQ when
hyperglycaemic, 2 remained
the same and 2 had a slight
increase
Results
Stat sig. decrease in 5/12 tasks
following mild hypoglycaemic
episode despite complete
resolution of symptoms
The same two psychologists
conducted all tests and each
patient was tested by the same
psychologist on both occasions
Blinding:
Patients and the testing
psychologist were blinded to
the order of testing
Randomisation:
stated
Patients were randomised to
either euglycaemia or
hyperglycaemia in the first
instance, and then received the
crossover treatment at least six
months later
Comments
Suggests time lag in resolution
of cognitive function after mild
hypo
Comparative
RCT
(crossover)
Design
Comparative
III-2
II
Level
III-2
2000
Rosen DS, Blum RW, Britto M, Sawyer SM, Siegel DM, Society for Adolescent Medicine: Transition to adult health care for adolescents and young adults with chronic conditions: position paper of the
Society for Adolescent Medicine. Journal of Adolescent Health. 33:309-311, 2003
Austroads: Assessing Fitness to Drive. Guidelines and Standards for Health Professionals in Australia. Sydney, Austroads Incorporated, 2001
International Diabetes Federation. Position Statement. Diabetes and tobacco use: a harmful combination. 2003.
Diabetes UK. Information. Alcohol and Diabetes. 2003. London, Diabetes UK. Ref Type: Report
National Institute for Clinical Excellence. Eating Disorders: Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa, and related eating disorders. 2003. London.
Chapter 19: School
24
25
34
57
59
60
14
Ref No
4
299
12
13
14
15
Rovet 1997
Sansbury
1997
Rovet 1999
Hannonen
2003
21 children with
T1D and 10
healthy controls
16 children with
type 1 diabetes
28 T1D children
100 controls (50
boys, 50 girls)
mean age 13.1 +/2.5 years
103 T1D (50
boys, 53 girls),
mean age 13.5+/2.3 years.
T1D and one episode of severe
hypo
Normal controls
T1D with no hypo.
NEPSY (dev. Neuropsych
assessment)
Divided into 3 groups
Memory – Digit span
Phonological processes in T1D
with hypos scored
lower than controls (p<0.05)
Hypo seizure patients scored
lower (p<0.01)
Attention – T1D
without hypos had test scores
significantly lower
than controls (p<0.05)
Poor met control assoc with
lower vocab subtest scores.
Hypo seizures more likely to
have IQ decline (67% vs 14%,
p<0.05)
Behaviour checklist
Verbal IQ
Inc duration assoc with lower
matching figures score.
IQ poorer performance in early
onset (p=0.01)
Seizure history had lower
verbal IQ than controls
(P<0.01) but did not differ form
children with diabetes who had
no seizures who scored slightly
below controls.
Increased age assoc with
decreased IQ score
T1D attention scores lower
(p<0.05)
Reading and memory
impairment in early onset
groups
Of 136 eligible children
approached 103 agreed to
participate (76%).
Higher depression score after
hypo night (p=0.03)
IQ scores lower in early onset
and longer duration
Matching figures
WISC-R
Verbal subtests
WISC-R
WAIS-R
MMFFT for Attention
Mood assessment
WISC-R
Perceptual, fine motor,
visuomotor, visual memory
and attention
WISC-R
Follow up at 1, 3, 7 years
9 had hypoglycaemic seizure
HbA1c
Duration
Age at onset
Divided in 4 groups depending
upon age of onset and length of
duration
11
Holmes 1985
15 healthy
controls
41 children with
T1D
Unclear methodology
Patients and controls recruited
from Hosp for Sick Children,
Toronto, Canada.
Comparison between controls
and diabetes subjects were by t
tests and ANOVA’s.
Comparative
Case series
Case series
Comparative
Case series
III-2
IV
IV
III-2
IV
300
17
18
19
Northam
1998
Northam
2001
Schoenle
2002
64 T1D children
between the ages
of 7 and 16 years
Follow up study
from Northam 98
study
90 patients (aged
6-17 years, mean
12.1 +/- 2.9) who
had
been
previously
assessed soon
after Dx and 2
years later were
re-evaluated 6
years after onset
of diabetes.
84 controls
(12.1+/-2.8 years,
p=NS).
123 children (3-14
years) with recent
T1D onset were
compared with
129 community
control subjects
40 sibling controls
63 new T1Ds
Longitudinal study looking at
long term metabolic control
and hypoglycaemia on
intellectual development.
Standardized measures of
general intelligence, attention,
speed of processing, memory,
learning, executive skills and
behavioural adjustment soon
after diagnosis and 2 years
later.
Neurocog function examined at
onset and 1 year later
16
Rovet 1990
Assessed at least 4 times
using German version of
the Hamburg Wechsler
intelligence scale for
preschool children, and by
the Adaptive Intelligence
Diagnosticum
others
WPPSI-R
WISC-R and others
WISC-R
Severe hypo assoc. with lower
verbal
and
full-scale
intelligence quotient scores.
Significant performance
decline by 7yr and verbal IQ
between age 7 and 16 years
was observed in diabetic boys
diagnosed before the age of 6 (
not in those diagnosed later, not
in diabetic girls).
Attention, processing speed, &
executive skills were esp.
affected when onset was before
4 yrs old.
No diff
No differences in T1D and
controls at initial assessment
within 3 months of diagnosis.
After 2 years significant
decrease in vocabulary IQ
(P<0.01), block design P<0.05)
subtests. Multivariate group
differences were apparent on
speed of processing (p<0.05)
and learning (P<0.01) subtests,
reflecting smaller
developmental gains in children
with IDDM when compared
with control subjects.
Six years after onset of
diabetes, children with T1D
performed more poorly than
controls on verbal IQ (F=8.07,
p<0.01), ful scale IQ
(F=5.33.P<0.05) attention
(F=2.63, P<0.05), processing
speed (F=4.81,P<0.01), longterm memory (F=3.58,P<0.01),
and
executive
skills
(F=4.57,P<0.05).
both T1D with & without
scored lower compared
with controls (p<0.01)
Vocabulary decreased after 1
year (p=0.05)
Prospective longitudinal study.
Cohort of 64 patients analysed
out of a larger group of 164
patients being followed.
Selection based on having had
at least 4 out of 6 longitudinally
applied tests between ages 7
7 children with T1D and 17
control children were not
evaluated at 2 years.
prospective
longitudinal
case series
Comparative
Comparative
Comparative
cohort study
IV
III-2
III-2
III-2
301
Population
Intervention
Ref No
Insulin regimen during travel when crossing time zones.
Study
21.1
Outcome
Results
Comments
Design
Level
International Society for Pediatric and Adolescent Diabetes: ISPAD Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Medical Forum
International, 2000
5
19
20
Ref No
3
No studies were identified specifically addressing the benefits on glycaemic control of diabetes camps.
20.1
Male sex, diagnosis at a young
age, metabolic condition at
diagnosis and long-term
metabolic control(p<0.001),,
rather than experienced
hypoglycaemic
attacks
(p=0.21) are risk factors for
intellectual development.
and 16 years.
American Diabetes Association: Care of children with diabetes in the school and day care setting. American Diabetes Association. Diabetes Care 26:131-135, 2003
International Society for Pediatric and Adolescent Diabetes: Consensus Guidelines for the Management of Type 1 Diabetes Mellitus in Children and Adolescents. Zeist, Netherlands, Medforum, 2000
Ref No
4
20
21
19.2
The
deterioration
of
performance in boys diagnosed
at a very young age was not
associated with the occurrence
of severe hypoglycaemic
episodes but was correlated
with the degree of metabolic
deterioration at diagnosis and
with high long-term average of
HbA1c.
302
BD patients were advised to take
between 15-20% of TDD before
each meal
Individually advised to adjust
insulin depending on flight and
regimen.
Basal bolus patients were advised to
continue taking short-acting insulin
with each meal during travel, but no
intermediate acting.
Advised to increase their insulin
dose if travelling west, and decrease
if travelling east. Also have 2-4
units of short-acting if BGL>15
mmol/L
Does not report on glycaemic
control
Gives very little details about
what patients actually did with
their intermediate acting
insulin.
Small numbers
Dose not specify individual
insulin regimens
Does not mention age range.
Small numbers (n=27)
Case series
Case series
National Center for Complementary and Alternative Medicine (NCCAM) and NIH. What Is Complementary and Alternative Medicine (CAM)? 2003. http://www.nccam.nih.gov/
Department of General Medicine, Royal Children's Hospital, and Melbourne. Use of Complementary and Alternative Medicines for Inpatients. 2003.
http://www.rch.org.au/genmed/CAMguidelines.htm.
Ref No
1
10
13
Mean BGL same for east and
west travel, but higher for
travel days than days at home
Patients were happy with this
simple system and reported no
problems.
Eastward travel reduced insulin
dose 2.6% of total daily dose
per time shift hour
Westward travel: increase in
insulin 3.1% of total daily dose
per time shift hour.
No Level I or II studies were identified for this chapter
22.1
BGL
Patient
satisfaction
Total insulin dose
required
Ref No
1
6
16 insulin treated
patients (age
range 9- 69)
2 on basal bolus
regimen, and 14
on BD injections
27 T1D patients
5
Jones 94
21.2
4
Sane 90
IV
IV
303

Clinical practice guidelines: Type 1 diabetes in children and adolescents

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