Diagnosis of diabetes-associated periodontitis by measuring

2015/9/25
Medical and dental collaborations in
Tokushima University Hospital
and Tokushima Dental Association
Toshihiko Nagata
Department of Periodontology and Endodontology,
Institute of Biomedical Sciences, Tokushima University Graduate School
1
COI Disclosure
Speaker: Toshihiko Nagata
The speaker has no financial conflict of interest
to disclose concerning this presentation.
Tokushima city
Population: 261,185 (2015)
The capital city of Tokushima
prefecture
Tokushima
station
Tokushima city
Bizan
Naruto whirlpoors
Tokyo
Kyoto
Yoshino river
Kobe
Osaka
Fukuoka
Tokushima
Awa-odori
Puppet theater
3
1
2015/9/25
Number of case/100,000 people
Mortality rate due to DM in Tokushima prefecture
Japanese average
Tokushima citizens
2000
1993 1995
2008
2005
(from Home page of Tokushima prefecture)
Diabetes (DM) mortality rates of Tokushima prefecture have been worst one
in Japan for recent 14 years. Although “Campaign for decreasing DM” has been
performed in Tokushima prefecture, the worst record is continuing.
4
Tokushima University Hospital,
Medical hospital building
Tokushima University Hospital,
Dental hospital building
Pf. Matsuhisa
Pf. Funaki
In Tokushima University Hospital,
Clinical Research Center for Diabetes
and Diabetes Therapeutics and
Research Center were established in
2007 and 2010 for the purpose of the
decrease of diabetes patients in
Tokushima prefecture.
5
Signs of DM-improvement in Tokushima prefecture
Mortality rate due to diabetes
Downward trend
in Tokushima
despite an upward trend
nationally
(Number of cases per 100,000 people)
2008
20
2012
19.5
20
18.0
Prevalence of diabetes in Tokushima
(over 40 years old)
30.0%
24.7%
25.0%
DM
有病者
17.3
decrease
14.3
15
15
IGT
予備群
22.5%
10
10
5
5
20.0%
13.9%
11.5%
15.0%
decrease
10.0%
5.0%
0
Kagawa
Toyama
Aomori
Iwate
徳 岩 鳥 青 香 富
島 手 取 森 川 山
Tottori
Ibaragi
Ibaragi
Tottori
Tottori
徳 鹿 福 鳥 青 茨
島 児 島 取 森 城
島
Aomori
Aomori
increase
0
Tokushima
H22
2010
Kagoshima
Kagoshima
2003
H15
0.0%
National 2002 : 22.6% → 2007: 29.6%
Fukushima
Fukushima
11.0%
Tokushima
Tokushima
10.8%
6
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2015/9/25
＜In terms of dental science＞
Two important points concerning the relationship between
diabetes and periodontal disease
1. Diabetes patients easily suffer from periodontitis
and its condition tend to be severe.
２. The presence of periodontitis affects glycemic
control of diabetes patients.
Diabetes
Periodontitis
Two-way relationship
7
Diabetes-associated periodontitis
A 42-y-old man.
Type 2 diabetes
A 50-y-old man.
Type 2 diabetes
・Severe gingival inflammation
・Multiple gingival abscess
・Marked bone resorption
・Delay of wound healing
8
Alveolar bone loss and tooth loss in patients with diabetes and
nephropathy （Collaboration study with Kawashima Hospital in Tokushima）
*
*
Alveolar bone loss
(%)
Number of tooth loss
40
30
20
10
0
DM
DM+HD
HD
*
20
15
10
5
0
DM
DM+HD
HD
Mean ± SE
Mean ± SE
*P<0.05
*P<0.05
DM: Outpatients with diabetes
(n = 51)
DM+HD: Dialysis patients with DM-nephropathy (n = 32)
HD: Dialysis patients with renal diseases
(n = 84)
DM + HD patient
9
3
2015/9/25
First visit
Periodontal therapy of a diabetic patient #1
（66 year-old woman：type 2 diabetes、hypertension、breast cancer）
After the initial therapy
10
The change of HbA1c level before and after periodontal therapy
08/10/30
76┘EXT
HbA1c
08/11/21
└7EXT
09/2/4
54┘EXT
8
7
6
5
4
Rate of PD> 4mm 27.5%
Rate of BOP 40.0%
Rate of PD> 4mm 7.4%
Rate of BOP 29.6%
Average HbA1c 6.52
Average HbA1c 5.45
11
First visit
Periodontal therapy of a diabetic patient #2
（57 year-old woman：type 2 diabetes, RA, hypertension,
endocarditis）
After the initial therapy
4
2015/9/25
The change of HbA1c level before and after periodontal therapy
09/6/10
RP) Antibiotics
HbA1c
09/8/13
6432┴23 EXT
7.5
7
6.5
6
5.5
5
Rate of PD>4 mm 16.7%
Rate of BOP
2010.01
2009.11
Rate of PD> 4mm 11.5%
38.5%
Rate of BOP
6.6
Average HbA1c
Average HbA1c
2009.12
2009.10
2009.08
2009.09
2009.07
2009.06
2009.05
2009.03
2009.04
2009.01
2009.02
2008.11
4
2008.12
4.5
11.5%
6.2
HbA1c level decreased parallel to the number of bacteria
in periodontal pockets
Periodontal pockets
Blood contents
＊
After
treatment
＊
(%)
12
6
HbA1c
8
6
4
2
Before
treatment
＊
(pg/ml)
12
10
TNF-a concentration
Bacteria number
(10N)
HbA1c
TNF-a
Number of bacteria
4
10
8
2
6
0
Before
treatment
(＊P < 0.05, Wilcoxon’s rank test)
After
treatment
Before
treatment
After
treatment
(Iwamoto et al, J Periodontol, 2001)
Treatment of periodontitis is
associated with HbA1c
reduction. （Meta-analysis）
Effect of Periodontal Treatment on
Glycemic Control of Diabetic Patients.
A systemic review and meta-analysis.
Diabetes Care 33: 421-427, 2010.
Studies described a research population of
type 2 diabetic patients in whom glycemic
control improved after periodontal therapy
compared with the control group.
(0.40% reduction of HbA1c after the therapy)
15
5
2015/9/25
Guidelines “Periodontal therapy in diabetic patient”
from Japanese Society of Periodontology
First edition
2009.6
Second revised edition
2015.3
16
A poster published
in medical associations
To diabetic patients:
When diet- and
physical-trainings are
not effective, it is
necessary to doubt
the possibility of
periodontal disease.
（Recommendation to
check in dental office.）
Common risk factors
（Aging，Smoking，Stress etc.）
Diabetes
Two-way relationship
Periodontitis
Weakened immune system
Increased infection susceptibility
Delayed wound healing
Reduced local defense functions
Diabetic patients easily suffer from periodontitis
Local factors
Insulin resistance
appears in various cells
in the body
⇩⇩⇩
Periodontpathic bacteria
Lipopolysaccharide (LPS)
Local factors invade
in systemic circulation
Interleukin
TNF-a
Prostaglandins
Periodontitis affect diabetic conditions
18
6
2015/9/25
Periodontitis affect sysytemic conditions
Diabetes
Infectious endocarditis
Periodontitis
Cardio and Cerebral vascular
diseases
Low-birth-weight baby
Aspiration pneumonitis
Rheumatoid arthritis
Chronic nephritis
Diabetes seminar
Diabetes-periodontitis seminar for patients with diabetes and their family
(Tokushima University Hospital)
20
Oral Care Center in Tokushima University Hospital
・Oral care for medical admission patients
before and after their medical surgery.
21
7
2015/9/25
The effects of bedside oral care to
patients before systemic surgeries
Oral care shorten the hospitalization
Cardiovascular Surgery
Oral Surgery
Digestive Surgery
Pediatrics
Hematology
Tokushima newspaper: 2014.10.19
22
The location of Anan city, Tokushima prefecture
Tokushima
Anan
（Population：75,000）
23
Medical and dental collaboration for diabetic patients in Anan city
2011.11.7 NHK 「Evening network・Oral health protects systemic condition」
24
8
2015/9/25
Dentists introduce dental
patients to medical doctors.
2011.11.7 NHK 「Evening network・Oral health protects systemic condition」
25
Clinical meeting by medical doctors, dentists,
nurse and public health nurses
Medical doctors
Dentists
Public health nurses
Nurse
2011.11.7 NHK 「Evening network・Oral health protects systemic condition」
The introduction of patients, who show diabetic symptom,
from dentists to medical doctors may be a good way for the
increase of medical examination rate in diabetes.
26
Data was obtained from 865 dental patients (mean age 70.0）.
Patients with high CPI score tend to have high HbA1c.
9
2015/9/25
“Close to 20% of dental patients
were found to have pre-diabetes
as a result of dental-office
screening”
（2015.5.15 MEDPAGE TODAY）
The introduction of patients, who show diabetic symptom,
from dentists to medical doctors may be a good way for the
increase of medical examination rate in diabetes
28
Dentists may have a chance to find diabetic
patients who do not know their glycemic conditions
1. Dentists recommend them to check in medical clinic
from the health examination data and periodontal
examination data. (The trial in Anan city)
2. Use of glucose-meter in dental office.
3. Study on the dental specific determination method
for the screening of glycemic conditions
29
The study on the diagnosis of diabetic periodontitis using
gingival crevicular fluid (GCF)
1) GCF collection using a paper strips (Less-invasive method)
Measurement of GCF volume
２）Dilution of GCF with PBS-based solution
・Dulbecco’s PBS(-)（Nissui）
・0.9mM CaCl2
・0.33mM MgCl2・6H2O
Dilution to PBS
GCF paper
３） Determination
of marker proteins
（ELISA）
Centrifuge
GCF extraction
30
10
2015/9/25
Results
① Glycated albumin (GA) and calprotectin (CPT) in GCF were determined.
・High GA levels were detected in diabetic patients (DM and DM-P).
・High CPT level were detected in periodontitis patients (P and DM-P).
Diagnostic markers
Total GA (μg/site)
H
DM
P
DM-P
4.2
18.0 *
5.9
28.4 *
7.1
37.2 *
2.8
25.5 *
Total CPT (ng/site)
108.5
115.5
257.4 **
236.4 **
CPT concentration (μg/μl）
0.19
0.24
0.12
0.18
GA concentration (μg/μl）
* Statistically significant difference from H, P (P<0.01).
** Statistically significant difference from H,DM (P<0.01).
② There was a positive correlation between GA in GCF and HbA1c and GA in blood.
③ GA in GCF → Diabetic marker
CPT in GCF → Periodontitis marker
31 )
( J. Periodontol 85: 1667-1675, 2014
The determination of GA and
CPT from GCF is useful for the
diagnosis of diabetic
periodontitis.
( J. Periodontol 85: 1667-1675, 2014 )
Medical and dental collaborations for the diagnosis of
diabetes and periodontitis
Introduction of doubtful patients
Correct diagnosis of diabetes
Determination of
biomarkers such as
GA and CPT
Non-invasive sampling
Diagnosis of diabetic
periodontitis
（Screening of diabetic condition）
Early finding of diabetes
Inhibition of diabetic complications
33
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2015/9/25
Collaborators
Tokushima Univ Hospital Clinical Research Center for Diabetes
Pf. Funaki M、Drs. Shikama Y、Bando Y、Hiroshima Y
Tokushima Univ Diabetes Therapeutics and Research Center
Pfs. Matsuhisa M、Matsumoto T
Tokushima Univ Hospital, Dept of Oral Medicine
Pf. Azuma M、Drs. Aota K、Yamamura Y
Kawashima Hospital Tokushima
Tokushima University Graduate School
Department of Periodontology and Endodontology
（Tokushima University Hospital, Dept of
Periodontology）
Drs. Kido J、Ohishi K、Naruishi K、Ninomiya M、
Drs. Inagaki Y、Horibe M、Yoneda S、Mihara C、
Drs. Bando M、Nakajima Y、Sakamoto E、Murat H、
Drs. Ikuta T、Kajiura Y、Shinohara H、Hashimoto M、
Ms. Shimada.
Drs. Shima K、Mizuguchi J、Komatsu M、Bando T
Tokushima Teishin Hospital
Dr. Saio H
Tokushima Dental Association
Dr. Okamoto Y
34
12