Diabetes and Periodontal Disease The Relation
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Transcript of Diabetes and Periodontal Disease The Relation
Periodontal Inflammation and Diabetes: a two way relationship
Kaumudi Joshipura BDS, MS, ScD
Center for Clinical Research and Health PromotionSchool of Dental MedicineUniversity of Puerto Rico
Harvard University
2
Periodontitis Caries
Tooth loss
Common Risk FactorsAgeSmokingObesity, DiabetesPhysical ActivityGeneticsRaceAlcoholComorbidityMedications
Systemic Inflammation Nutrition (Body Composition,
(Biomarkers) Dietary intake; Nutritional Status) Dyslipidemia
Adverse Pregnancy Outcomes
Obesity
CHDPAD
Stroke
Diabetes
Kidney DiseaseCancer
Fluoride
Access to Care
HypertensionAtherosclerosis
Microbes
Pre-eclampsiaGestationalDiabetes
Pre-diabetes
Arterial Stiffness
Biological Pathways: Periodontal Disease, Systemic Inflammation and Cardiometabolic Conditions
Dental Caries • Cavities are holes or structural damage to the teeth.
• There may be no symptoms, but if present, may include:– Toothache or painful sensation
in the teeth, especially after consuming sweet drinks or hot or cold food
• Risk factors include: –Poor oral hygiene –Fermentable carbohydrates
Periodontitis• It is an infection and
inflammation affecting the soft tissues and bone that support the teeth.
• Periodontitis occurs when infection and inflammation of the gums (gingivitis) progresses to involve other surrounding tissues.
Healthy Gingiva
Periodontal Disease
Healthy gingiva Periodontal Pocket
Pocket Depth
Attachment Level
6mm 6mm
Bone Loss
Gingival RecessionCauses:
• Periodontal Disease• Traumatic tooth cleaning
technique• Local irritants (plaque or
calculus)• Orthodontic tipping • Provisional crowns • Extraction of adjacent
teeth • Occlusal forces
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U.S. Adults Periodontal Disease Prevalence (≥1 site Pocket Depth ≥4mm)
NHANES III, 1988-94
Adapted: Burt and Eklund, 2005
NHANES III, 1988-94
U.S. Adults Cumulative Periodontal Disease Severity ≥1 site Attachment Loss by Age
Adapted: Burt and Eklund, 2005
Established risk factors
• Microbes• Age • Male gender • Race • Genetic factors
• Tobacco • Diabetes • Malnutrition • Systemic
disease
Potential novel risk factors • Obesity • Physical activity • Alcohol• Calcium • Vitamin D • Antioxidants, fiber, other…..
Predictors of Periodontal Disease
These act indirectly through other risk factors:• Education• Employment • Income• Regular dental visits• Marital status• Dental insurance
Prognostic factors• Plaque control • Triclosan • Scaling and root planing • Other professional treatment
Impact of Periodontal Disease
Periodontal Disease
Bad Breath
Recession
Mobility
Root Caries
Hypersensitivity
Aesthetics
Systemic Diseases
Tooth Loss
Chewing Difficulty
DietPain
Systemic Inflammation
Biological Pathways: Periodontal Disease, Systemic Inflammation and Insulin Resistance
Periodontal Disease
Major Common Risk FactorsAge Physical ActivityGenetics DietSmoking Obesity
Type 2 Diabetes*
β-Cell Dysfunction Insulin resistance
Glucose Abnormalities
Dyslipidemia (HDL, TG) Adiponectin
Systemic Inflammation (CRP, Il-6, TNF-∞)
Diabetes
Metabolic Syndrome and Periodontitis
Authors Population Results OR (95% CI)
Morita, T., et al.2009
Tokyo, JapanN= 2478 adult Age: 43.3 years
Any vs. No positive component OR =1.8 (96% CI = 1.4-2.3)
≥ 3 vs. No positive componentOR= 2.4 (96 % CI = 1.7-2.7)
Li, P., et al.2009
ChineseN= 208 adults
OR = 9.9 (95% CI: 1.50 - 65.24) attachment loss >33% to 67% of sites
OR = 15.6 (95% CI: 2.20 -110.43) attachment loss >67% of sites
D'Aiuto, F., et al.2008
NHANES IIIN=13,994
Aged ≥ 17 yr
Severe periodontitis vs. No periodontitisOR = 2.31 (95% CI 1.13-4.73)
10% increase in gingival bleeding, OR = 1.12 (95% CI 1.07-1.18)
10% increase in periodontal pockets, OR = 1.13 (95% CI 1.03-1.24)
Components of metabolic syndrome
• Abdominal obesity• Atherogenic dyslipidemia
• Hypertension
• Insulin Resistance/Diabetes
Association between Obesity and Periodontitis
Authors Population Results OR (95% CI)
Al-Zahrani et al. 2003
NHANES III N=13,665
Ages: 18-90 yrs
BMI > 30 vs. BMI 18.5-24.9 (ref)60-90 yrs: OR 1.20 (0.89-1.61)
WC: >88 cm women; >102 cm men60-90 yrs: OR 1.14 (0.86-1.50)
Borges-Yanez et al. 2006
MexicoN=473
Ages: > 60 yrsBMI > 30 kg/m2
OR=0.93 (0.85-1.02)
Linden et al. 2007MenUK
N=1,362Ages: 60-70 yrs
Low –threshold:BMI>30 kg/m2: OR:1.77 (1.20–2.63)>30% Wt gain: OR=1.33 (0.95-1.86)
High-threshold:BMI >30 kg/m2: OR:1.55 (0.82–2.93)>30% Wt gain: OR=1.65 (0.95-2.87)
Studies on Obesity and Periodontitis among older adults
Relationship between abdominal obesity and periodontitis in elderly Puerto Ricans
• Puerto Rican Elderly Dental Health Study (PREDHS)– Representative sample of adults age 70 and older San Juan Metropolitan area (N=183)
• Exposures: waist circumference, waist-to-hip ratio
• Outcome: moderate and severe periodontal disease
• Multivariate logistic regression
• Adjusted for age, gender, smoking, education, diabetes status, physical activity, total fruit and vegetable intake.
• Models for moderate and severe periodontitis additionally adjusted for number of teeth.
Relationship between obesity and periodontitis in elderly Puerto Ricans• Multivariate-adjusted
Moderate: OR=5.63 (1.44; 22.06)Severe: OR=1.12 (0.37; 3.41)Upper tertile % of sites with AL ≥ 3: OR=3.59 (1.37; 9.41)Upper tertile of Mean AL: OR=2.07 (0.84; 5.10)
• Multivariate-adjusted Moderate: OR=4.03 (0.92; 17.65) Severe: OR=1.98 (0.58; 6.80) Upper tertile % of sites with AL ≥ 3: OR=1.99 (0.74; 5.31) Upper tertile of Mean AL: OR=2.49 (0.91; 6.77)
Muñoz, IADR, 2009
Association between Dyslipidemia and Periodontitis
Periodontitis and Dyslipidemia
Joshipura et al, JDR 2004
No periodontal disease N
=377
Periodontal diseaseN = 91
% difference
p-value
LDL 108.5 120.0 11 0.001*
ApoB 117.6 129.0 9.7 0.002*
HDL 56.5 55.2 -2.4 0.68
Cholesterol 224.9 246.3 9.5 <0.001*
Clinical Trial for the Treatment of Periodontitis and Lipids
• Fifty patients (31 females and 19 males, age 36-66 yr) who had ≥ 3 pockets with a PD S:4 mm
• Groups: – Control: biochemical and periodontal evaluations– Treatment: periodontal treatment
• Measurements taken at baseline and end of study – Dental Assessment: PD, PI, GI, AL, BOP– Biochemical measurments: LDL, HDL, VLDL, TG
OZ, South Med J, 2007
Clinical Trial for the Treatment of Periodontitis and Lipids (cont.)
• Greater reduction of pocket depth and attachment loss in treatment group than in control group (11 % vs. 7% and 24.5% vs. 0%, respectively)
• Treatment Group: Significant reduction of 12.7% in total cholesterol and 25.7% in LDL compared with baseline values.
• Control Group: NS reduction 3.9% in total cholesterol and 2.5% in LDL
• There were also significant differences in total cholesterol and LDL levels between the two groups
OZ, South Med J, 2007
Periodontitis and Diabetes
Diabetes and Periodontal Disease
Oral care report 2001
Mechanisms for Diabetes-Perio Relationship
• Altered host response• Alterations in connective tissue and wound
healing • Microangiopathy• Alterations in gingival crevicular fluid• Altered subgingival microflora
(composition/virulence)• Hereditary predisposition
Taylor 2004 Compendium
Literature on Periodontitis and Diabetes
• Over 50 cross-sectional associations. Only few longitudinal studies
• A meta-analysis among type 2 diabetic patients showed an improvement after aggressive periodontal treatment, weighted mean difference of HbA1C before and after therapy of -0.40% (95% CI -0.77 to -0.04%, P = 0.03). Teeuw WJ, et al. Diabetes Care. 2010
Not clear if A1c improvement due to perio improvement or due to antibiotics
Periodontal Disease and Incidence of Type 2 Diabetes Mellitus
• The multivariate Cox RR for periodontitis (comparing moderate/severe vs. none/mild) and type 2 DM– 1.17 (0.97-1.42) in men vs. 1.20 (0.96 -1.50) in women
• Updated Periodontitis – 1.32 (1.15- 1.51) in men
• Tooth loss (≥1 vs. 0 teeth lost during follow-up):– 1.25 (1.12 -1.40) in men vs. 1.14 (1.06 - 1.22) in women
• The associations among men persisted among never smokers. • Confounders: age, smoking, family history of diabetes, physical
activity, body mass index, alcohol, diet (sugar-sweetened soft drinks, fiber, glycemic load and polyunsaturated: saturated fat ratio) and in women-menopause status and post-menopausal hormone use.
Joshipura, ADA, 2008
Periodontal Therapy and Insulin Resistance
• Only one clinical trial among type 2 diabetes patients showed that periodontal therapy was associated with decreased insulin resistance. Talbert J et al. J Dent Hyg. 2006
• Some RCTs showed positive findings; others showed no significant reduction in the level of plasma glucose.
• Inconsistent results from cross-sectional studies
Periodontitis as a risk factor for Diabetes
NHANES I • Periodontal pockets index 3 vs. Healthy
– OR = 2.26, 95% CI: 1.56-3.27
• Periodontal pocket index 4 vs. Healthy – OR = 1.71, 95% CI: 1.09-2.69
• Periodontal pocket index 5 vs. Healthy – OR = 1.50, 95% CI: 0.99-2.27
Demmer et al., Diabetes Care, 2008
Conclusions for Diabetes Periodontitis Association
• The association between periodontitis and type 2 diabetes is potentially bidirectional, but neither direction has been established
• Periodontal treatment including antibiotics could lead to improvement in HbA1c
• Periodontitis is associated with several risks factors for diabetes as well as with diabetes complications
• More well designed longitudinal studies and clinical trials are needed
Complications of Diabetes
• Microvascular complications include – Neuropathy– Nephropathy– Vision disorders
• Macrovascular complications include – Heart disease– Stroke – Peripheral vascular disease
• Periodontal disease is also considered a complication of diabetes
Complications of Diabetes
• Microvascular complications include – Neuropathy– Nephropathy– Vision disorders
• Macrovascular complications include – Heart disease– Stroke – Peripheral vascular disease
• Periodontal disease is also considered a complication of diabetes
Diseases Stroke (M) PAD (M) CHD (M) CHD (F)
Baseline Teeth Multivariate Relative Risks
25-32 1.0 1.0 1.0 1.0
17-24 1.6* 1.2 1.1 1.1
11-16 1.8* 1.4 1.4* 1.3
0-10 1.8* 1.1 1.4* 1.6*
Periodontal Disease 1.3* 1.3* 1.0 1.0
Incident Tooth Loss
During follow-up 1.3* 1.4* 0.9 -
Summary of our work in HPFS (Males) and NHS (Females) relating perio and CVD
HPFS Multivariate Results No
periodontal disease N
=377
Periodontal disease N = 91
% difference
p-value
CRP 0.47 0.61 30 0.02* Fibrinogen 286.5 288.4 1 0.61 Factor VII 99.7 101.0 1 0.36 IL -6 1.5 1.7 11.8 0.44 TNFR1 1129 1092 -3 0.22 TNFR2 1656 1610 -3 0.31 t-PA 15.9 17.6 11 0.001* vWF 109.0 121.4 11 0.001* LDL 108.5 120.0 11 0.001* ApoB 117.6 129.0 9.7 0.002* HDL 56.5 55.2 -2.4 0.68 Cholesterol 224.9 246.3 9.5 <0.001*
Joshipura et al, JDR 2004
NHS Results
No periodontal
disease N =229
Periodontal disease N = 152
% difference p-value
CRP 0.19 0.26 35.8 0.01* ICAM 332 356 7.4 0.02* VCAM 579 596 2.9 0.26 E-selectin 44 51 17.0 <0.001* Fibrinogen 295 307 4.0 0.17 IL -6 1.7 1.7 1.5 0.84 TNFR1 1222 1258 2.9 0.40 TNFR2 2248 2369 5.4 0.07 LDL (mg/dl) 133 144 8.2 0.04
Adjusting for age, smoking, BMI, physical activity, aspirin use, alcohol use, CHD case-control status and diabetes
Clinical Trials for Biomarkers
• Tonetti et al. NEJM.
Intensive vs. regular perio care 2-6 months
Flow-mediated dilation E-Selectin
• D’Aiuto et al. Am Heart J.
Intensive vs. regular perio care. 2-6 months
CRP, IL-6, Total Cholesterol and CVD composite scores
92%
96%
100%
104%
108%
112%
116%
Fruits Fruits withoutJuice
Vegetables Dietary fiber
None
1 to 10
11 to 16
17 to 24
25 to 32
Percentage of Edentulous Subjects' Dietary Intake
Hung, CDOE, 2005(Adjusting Age, Smoking and Physical Activity)
0
0.2
0.4
0.6
0.8
1
1.2
<3 3-4 4-5 5-6 6-8 >8
Fruit and Vegetable Intake (Servings/Day)
RR
an
d 9
5%
CI
Intake of total fruits and vegetables and risk of Ischemic stroke in the NHS and HPFS
Joshipura et al., JAMA, 1999
Future DirectionsOral and systemic association
• Additional cohort studies in different populations including developing countries
• Additional systemic outcomes
• Evaluate pathways with exposures, outcomes and mediators in the same models
• Evaluate role of periodontal microorganisms
• Evaluate role of genetic factors
• Clinical trials where feasible
Role of Physicians in Oral Health
•Emphasize prevention of oral disease and retention of teeth.•Age-specific advise•Annual Routine Physical:
• Include basic oral exam• Oral cancer visual screening• Referrals to dentist
•Systemic Disease, Treatments: Communicate impact on oral health to dentists and patients.•Control of diabetes.•Nutrition counseling for better oral and general health and recommend prosthesis when needed.
Dr. Alberto AscherioDr. Graham ColditzDr. Constant CrohinDr. Chester DouglassDr. Sue HankinsonDr. Frank HuDr. Hsin-Chia HungDr. Anwar MerchantDr. JoAnn MansonDr. Waranuch PitiphatDr. Eric RimmDr. Christine RitchieDr. Frank SpeizerDr. Walter Willett
AcknowledgementsGrants:R01DE12102R01DE017176BOHCR – DE1184 R03DE14004Office of Dietary Supplements, Florida Department of CitrusK-24 DE016884RCMI – G12 RR 03051RCMI CRCS21MD001830
Acknowledgements
PREDHS Team:Dr. Maria L. AguilarMichael BrunelleDr. Ana Luisa DávilaJenifer GuadalupeMonik JiménezSasha MartínezDr. Mauricio MonteroFrancisco MuñozVanesza RoblesDr. Enrique SantiagoJenifer TorresDr. Sona TumanyanYari Valle
SOALS Team:Dr. Cynthia PerezJennifer ColonJhezanuel GoncalvesGustavo SanchezKristian PoventudReinaldo DelizDr. Pedro HernandezOelisoa Andriankaja Dr. Cristina PalacioJose Luis VergaraBarbara GuzmanLaritza BerriosLumarie CuadradoAlberto CarreraDr. Maribel Campos