Managing gastrointestinal complications of diabetes

GI manifestations of diabetes
Professor Qasim Aziz, PhD MRCP
Neurogastroenterology Group,
Wingate Institute of Neurogastroenterology,
Centre for Gastroenterology, Blizard Institute
Barts’ & The London School of Medicine of Dentistry, London, UK
Background
• Postulated that a change to
a western diet/increased
urbanization
• Management is increasingly
refined leading to
improvements in prognosis
• Increase in complications –
associated with degree of
glucose control rather than
longevity of diagnosis 1, 2
1.Bytzer, Talley et al, Arch Int Med
2001
2.Kim et al, World J Gastro 2010
Who is the odd one out?
1. Alan Alda (MASH)
2. Al Pacino
3. John Travolta
GI manifestations in diabetes
•
4.
76% of diabetic patients
attending outpatients
report significant GI
symptoms4
Feldman & Schiller. Disorders of GI motility
associated with diabetes mellitus. Ann
Intern Med 1983;98:378-84
Symptom
Outpatients
n =136 (%)
Constipation
82 (60)
Abdominal pain
46 (34)
Nausea & vomiting
39 (29)
Dysphagia
37 (27)
Faecal incontinence
27 (20)
Diarrhoea
30 (22)
No GI symptoms
32 (24)
Talk overview
• Mechanisms of normal gastrointestinal (GI) motility
• Pathogenesis of dysmotility in
diabetes
• Management
Mechanisms of normal GI motility
• Motility is the term given to the complex series of events
that comprise:-
• Ingestion of nutrients
• Facilitation of peristalsis
• Transiting of nutrients across absorptive surfaces
• Expulsion of waste
Normal Migrating Motor Complex
Normal Migrating
Motor Complex (MMC)
D
Phase I
• Quiescence
J
15-30 minutes
D
• Irregular
contractions
Phase II
J
60 minutes
D
Phase III
• Propagated
contractions
J
4-7 minutes
Interdigestive
90 minute cycle
Camilleri M, Phillips SF, Gastroenterol Clin North Am. 1989;
18:405
Neural control of normal GI motility
• Over-riding control is from the central
nervous system
• GI tract capable of autonomy via the
enteric nervous system
•
“Little brain”
• Large influence from the autonomic
nervous system, particularly the
parasympathetic (PNS)/vagus nerve
• PNS denervation results in:
•
•
Decreased GI tract tone
Reduction in peristalsis
Dysmotility in diabetes
• GI motor & sensory dysfunction frequently
occurs in diabetics
• Significant morbidity and reduction in
health related quality of life in those
diabetics with GI symptoms 3 (p<0.001 vs. healthy
population)
3.Farup, Quigley et al, Diabetes Care
1999
Clinical sequelae of GI dysmotility in diabetes
• May manifest at any point in the GI tract
• Either in isolation or in combination
• Gastroparesis and intestinal enteropathy are the most
prevalent
• Natural history unclear
• Risk factors include5:• Elevated HbA1C
• Presence of diagnosis for >10 years
• Presence of established macro and micro vascular complications
5.Camilleri, NEJM 2007
Diabetes & GI dysmotility – the vicious cycle
Delayed
gastric
emptying4
Increased
complications
GI
symptoms
Poor
glycaemic
control
Impaired
nutrition
Delayed
absorption
of oral
medication
4.Rayner, Diabetes Care 2001
Symptomatology of gastic dysmotility in diabetes
Poor
glycaemic
control
Bloating
Early
satiety
Gastroparesis
Nausea
Vomiting
Symptomatology of GI dysmotility in diabetes
Diarrhoea
Constipation
Intestinal
Enteropathy
Incontinence
Bloating
SIBO
Pain
Mechanisms of dysmotility in diabetes - 1
• Mechanisms are complex and incompletely understood
• Diabetes affects multiple levels neuromuscular control of
GI motility
• Demyelination of the vagus nerve
• Loss of parasympathetic and sympathetic nerve fibres
• Degeneration of ICCs
Mechanisms of dysmotility in diabetes - 2
• Dysmotility traditionally attributed to irreversible
autonomic neuropathy
• Yet association between delayed gastric emptying &
presence of cardiovascular dysautonomia poor 6
• Why?
• Lack of tests to evaluate GI autonomic tone directly
• Is there another mechanism(s) at play?
6.Horowitz, Eur J Nuclear Med, 1991
Hypo/hyperglycaemia
• Changes in serum glucose have a profound effect on gut
motility 7
Thus,
GI
motor
function
• Compared with euglycaemic state (4-8mmol/L) gastric emptying
is is
delayed
in hyperglycaemic
state (16-20mmol/L),
p<0.04
highly
sensitive
to fluctuations
In type 2 patientsin
:- glycaemic state
• In type 1 patients 8:-
•
9
• Cross sectional study HbA1C inversely proportional to gastric
emptying
• Acute (insulin induced) hypoglycaemia accelerates
gastric emptying10
7.Horowitz, Eur J Nuclear Med, 1991
8.Fraser et al, Diabetalogica 1990
9.Horowitz et al, Diabetalogica, 1989
10.Russo, J Clin Endo Metab, 2005
Evaluation of diabetic gastroparesis
Gastric emptying
• Methods available
•
•
•
•
•
Gamma Scintigraphy
Breath Test using 13C-octanoic acid
Electrical Impedance Tomography
Ultrasound
MRI
Gamma scintigraphy
• Test meal: egg labelled with 99mTc, bread and
water
• Radioactivity of ROI is counted by gamma
camera
Image of the distribution of radioactivity
13C
breath test
• Test meal: egg labelled with 13C octanoic acid , bread
and water
• Breath samples are collected using dedicated bags
• 13C recovery within breath sample is analysed using
Isotope-selective infrared spectro-photometer (Wagner
Analysen Technik, Germany) to calculate lag phase & t1/2
13C
breath test (report)
Severity of gastroparesis
Approach to management of diabetic gastroparesis
Summary
Managing other symptoms in diabetes
Diarrhoea
Constipation
Intestinal
Enteropathy
Incontinence
Bloating
SIBO
Pain
Diarrhoea
• Exclude other conditions
• Coeliac disease
• Thyroid disease
• Anti-diarrhoeals
• Loperamide
• Treat for small bowel bacterial overgrowth
• Lactulose hydrogen breath test
• False positive’s and negatives
• Antibiotics (augmentin or ciproxin
• Probiotics (VSL 3)
metronidazole)
Constipation
• Exclude
• Hypothyroidism
• Dehydration
• Correct
• Dietary factors
• Laxatives
• Osmotic
• Stimulant
• Prokinetics
• Prucalopride (5HT4 receptor agonist)
Pain
• Treat small intestinal bacterial overgrowth
• Antispasmodics
• Worsen GI dysmotility
• If associated with painful peripheral
neuropathy
• Pregabalin / gabapentin
• Amitriptyline
Conclusions
We are in the midst of a global epidemic of diabetes
Gastroparesis and intestinal enteropathy are common
sequelae of dysmotility
Mechanisms of GI dysmotility are incompletely understood
Management is based on:
Judicious investigation
Symptomatic management of symptoms
Prokinetics
Centre for Digestive Diseases
Neurogastroenterology
Group