PPT (2 MB) - Institute for Oral Health

Institute for Oral Health Conference
Periodontal Disease and Diabetes: Exploring New Paradigms
November 26, 2007
“A A Diabetic Triangle: The Relationship Between Diabetes,
Obesity and Periodontal Disease”
By
Robert J. Genco, DDS, PhD
State University of New York Distinguished Professor
University at Buffalo Schools of Dental Medicine and Medicine
rjgenco@buffalo.edu

A Diabetic Triangle
I. Risk for Periodontal Disease
II. Diabetes Mellitus
A. Scope of the Problem
B. Diabetes and Periodontal Disease

Risk Factor Studies
Changing Concepts
Periodontal diseases are caused by
periodontal bacteria, the oral
microbiome.
Without these bacteria, there would
be little or no periodontal
destruction.

Why Study Risk Factors for
Destructive Periodontal Diseases
• To determine factors important in
increased susceptibility to
periodontal disease
• To provide the basis for risk factor
intervention

THE ERIE COUNTY STUDY
Study Design
1. Adults 25 to 74 years of age
2. Equal numbers of each decade
(25 to 34; 35 to 44; etc.)
3. Individuals of various socio-
economic classes included
Grossi et al. 1997

Periodontal Disease in Non-Insulin
Dependent Diabetes Mellitus
Objective:
To determine if relationship between diabetes and
destructive periodontal disease can be explained by oral
health measures.
Subjects: 1,342 dentate Pima Indians, cross-sectional
sectional
Periodontal Measurements: Clinical attachment loss, bone
loss
Oral Health Measurements: P.I., G.I., C.I., DMFT, F1
Emrich et al., J. Periodontol. 62:123, 1991

Longitudinal Study of Oral Health
Status of Pima Indians
Objective:
Population:
To determine the prevalence and the
incidence of periodontal disease and
its relationship to NIDDM.
2,273 Pimas; 701 were examined at
least twice.
Nelson et al., Diabetes Care 13:836, 1990

Relative Risk
Ratio of incidence rate of disease among those
exposed over the incidence rate among those
not exposed.
RR = Incidence rate exposed
Incidence rate unexposed
RR = 75.7 (incidence rate of diabetes) = 1.95
38.9 (incidence rate of normals)

Diabetes and Periodontal Disease:
Levels of Evidence
Diabetes Mellitus Type
Study Type 1 2 1, 2 Unk
Total
Longitudinal Studies 3/3 4/4 0 0 7/7
Cross-Sectional Studies 18/19 8/9 9/11 8/9 43/48
Total 21/22 12/13 9/11 8/9 50/55

AIM
To examine the relationship
between obesity and
periodontal disease in a
representative national
sample

POPULATION
12,367 non-diabetic individuals
from NHANES III study
• 20 to 90 years old
• No clinical diagnosis of DM
• Fasting glucose

Smoking
Stress
Genetics
Diet and
Exercise
Infection
Obesity
Markers/Mediators
•CRP
•II-6
•TNF-α
•Microalbuminuria
Insulin
Resistance
Impaired
Glucose
Tolerance
Type 2
Diabetes
Mellitus
lipids
adiponectin
Cardiovascular Disease
Renal Disease

Obesity and Insulin Resistance: Possible Role of Adipose
Tissue Macrophages (ATM)
Diet-Induced Obesity
Shift in ATM from M-2 anti-inflammatory (Il-10)
To M-1 proinflammatory
TNFα, Il-6 that
Block Insulin Action
Insulin Resistance
Lumeng, C.N. et al., J. Cl 117:175, 2007.

Population Affected by Risk Factors/Indicators
Factor/Indicator
% of
Population Affected
Cigarette smoking 26%
Diabetes mellitus 6% (12%)
Genetic factors
varies
Osteopenia/osteoporosis
PM females (20%)
Dietary calcium deficiency
1/3 below 50% RDA
Stress and inadequate coping 10%
Obesity 20%
Pre-existing existing periodontal disease
5-35% (age dependent)

Four Important Considerations for
Clinical Use of Risk Factor Analysis
1. Is there a convenient way to measure or
otherwise assess the risk factor
2. Is there a threshold level, above or below which,
the risk factor provides clinically significant
value
3. What are the consequences of false positive
and false negative results
4. Does risk factor intervention or identification
result in clinical benefit

Periodontal Disease Treatment TRIAD
Antiinfective Therapy
Risk Modification
Regenerative Therapy

A Diabetic Triangle
I. Risk for Periodontal Disease
II. Diabetes Mellitus
A. Scope of the Problem
B. Diabetes and Periodontal Disease

Worldwide Incidence of Diabetes: 2000 and 2010
14.2
14.2
17.5
17.5
23%
23%
26.5
26.5
32.9
32.9
24%
24%
84.6
84.6
132.3
132.3
57%
57%
15.6
15.6
22.5
22.5
44%
44%
9.4
9.4
14.1
14.1
50%
50%
World
World
2000:
2000:
151
151
million
million
2010:
2010:
221
221
million
million
Increase
Increase
46%
46%
1.0
1.0
1.3
1.3
33%
33%
Amos, A., McCarty, D. & Zimmet, P. The rising global burden of diabetes and its complications:
estimates and projections to the year 2010. Diabetic Med. 14, S1-S85 (1997).
Shoelson

Two Main Types of Diabetes
Type 1 diabetes
5-10% of total
Common in children
Insulin Requiring
Auto-immune
Destruction of the Islets
Type 2 diabetes
>90% of total
Mostly in adults, but
increasing in children
Not insulin requiring
Insulin resistant

Why is there an epidemic
Shoelson

1990
Diabetes prevalence
is increasing rapidly
1990-2000
91-92
92
93-94
94
6%
97-98
98
no data
99-00

Prevalence of Obesity in U.S. Adults
1990
No data 20%
Source: Mokdad, et al.
Shoelson

Prevalence of Obesity in U.S. Adults
2000
No data 20%
Source: Mokdad, et al.
Shoelson

Insulin Resistance and
β-Cell Function in
Type 2 Diabetes

Insulin Resistance:
Inherited and Acquired Influences
Inherited
Rare Mutations
• Insulin receptor
• Glucose transporter
• Signaling proteins
Common Forms
• Largely unidentified
Acquired
• Inactivity
• Overeating
• Aging
• Medications
• Hyperglycemia
• Elevated FFAs
INSULIN RESISTANCE

Insulin Resistance:
Causes and Associated Conditions
Genetics
Infections
(Periodontal)
Type 2
Diabetes
Obesity and
inactivity
Aging
INSULIN
RESISTANCE
Medications
Rare
Disorders
Hypertension
Atherosclerosis
Dyslipidemia

Possible Mechanisms of
Hyperglycemia’s Adverse Effects
• Sorbitol-myoinositol osmolarity changes (via aldose
reductase pathway) – AR inhibitors have not been effective
in clinical trials
• Oxidative-redox stress – Not effective at usual doses
• Non-enzymatic glycation reactions (AGE) – AGE blocker
trials stopped due to side effects
• • Activation of protein kinase C (PKC) – Diacylglycerol
(DAG) pathway – PKCβ isoform inhibitor trials are in
progress

HbA 1c Predicts Coronary Heart Disease in
Type 2 Diabetes
25
20
15
10
5
0
CHD mortality
Incidence (%) in 3.5 years
Low
7.9%
25
20
15
10
5
0
All CHD events
Incidence (%) in 3.5 years
Low
7.9%
*P

Diabetes: A Systemic Disease
Leading cause
of blindness
in working age
adults 1
Diabetic
Retinopathy
Periodontal
disease increased
in diabetes
Periodontal
Disease
Stroke
2- to 4-4
fold
increase in
cardiovascular
mortality
and stroke 2
Cardiovascular
Disease
Diabetic
Nephropathy
Leading cause of
end-stage renal disease 3
Diabetic
Neuropathy
Leading cause of non-traumatic
lower extremity amputations 4
National Diabetes Information Clearinghouse. Diabetes Statistics–Complications of Diabetes. (website)
http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#comp.

Diabetes
Mellitus
Periodontal
Disease
Effect of periodontitis on metabolic state.
Effect of periodontal therapy on glycemic
control.

Does Periodontal Disease Affect
Glycemic Control
Type 2 DM – Pima Indian study
Baseline HbA1c < 9% (normal < 6-6.5%). 6 6.5%).
Severe periodontitis at baseline (bone loss
>50% or attachment loss > 6 mm on one or
more teeth) significantly increased risk of
poor glycemic control at 2 year follow-up.
Taylor et al. 1996

Diabetes
Mellitus
Periodontal
Disease
Glycemic
Control
Periodontal
Therapy

Can Periodontal Treatment
Affect Glycemic Control
• 125 Type 2 DM patients, severe
periodontitis, , 5 groups
• Periodontal status, HbA1c and pooled
subgingival plaque sample at
baseline, 3 months, 6 months
Grossi et al. J Perio 1996, 1997

Change in Levels of glyHb After
Periodontal Treatment

Effect of Periodontal Disease on
Mortality in Type 2 Diabetes
Saremi A. et al., Diabetes Care 28(1):27-32, 2005
Study Design
• 766 diabetic Pima Indians (287 men, 479 women)
• Baseline PD measured
• Followed 12 years (range 0.3-16.0)
• 208 Natural deaths; cause validated

Results
• Baseline Periodontal Disease
44% males, 52% Females
• Death Rate/1000 pyrs, , (age-sex
adj)
P.D. – 28.3 (22.2 – 34.4)
Normal – 15.5 (10.7 – 20.2)

• Increased Death Rate for Periodontal
Disease vs. Normal from:
Cardiovascular disease – 2.7 (1.5 – 5.5)
Diabetic nephropathy – 4.1 (1.5 – 11.4)
Combined cardio-renal renal (adj(
adj) – 2.3 (1.5-4.0)

Public Health Implications
Resolution of periodontal infection appears to
improve glycemic control in Type 2 diabetics.
If it is shown that this also reduces diabetic
complications, then management of periodontal
infections becomes an important component of
treatment of diabetes.
“Medically necessary dental therapy”

PUBLIC HEALTH POLICY
• Full RCT needed to determine if periodontal disease is a modifiable
risk factor in patients with diabetes mellitus.
• Meanwhile
• Some insurers are covering periodontal care in patients with
diabetes mellitus, and other conditions related to periodontal
disease. Their economic data show a reduction in medical costs.
• CDC in the U.S. is developing self-reported triage methodology to
assist medical practices to identify patients who have periodontal
disease.
•
Eke PI and Genco RJ. J. Periodontol. 78(Suppl):1366
(Suppl):1366-1371, 1371, 2007.

ACKNOWLEDGMENTS
• Marc Shlossman
•Bill
Knowler
•George Taylor
• Sara Grossi
•Tom
DeCaro
•Todd Smith
•Aramesh
Saremi
• Rob Nelson
•Alex Ho
•Bob
Dunford
•George King
•Funding: U.S. National Institute of Dental and Craniofacial Research, Sunstar Inc.,
Colgate, Procter & Gamble, Atrix Laboratories, Inc., U.S. Centers for Disease Control

•Thank You!