Diabetes & Periodontal Health:

A Two-way relationship.

Francesco D’AiutoDMD, MClinDent, PhD, MRD RCS(Eng) RCPS (Glasg)

HEFCE Senior Clinical Lecturer/ Hon Consultant Periodontology Unit

Endothelial damage,

platelet aggregation

HSP 60,

molecular mimicry

Oral Cavity – Systemic Exposure

Periodontitis

Questions:

• Does Diabetes Mellitus affects Periodontal Health?

• Does Periodontal Health affects Diabetes Mellitus and its complications?

• Does periodontitis treatment improves metabolic control in people with Diabetes?

I. Type 1 diabetes* - previously known asjuvenile diabetes insulin-dependent diabetes

mellitus (IDDM)II. Type 2 diabetes* - previously known as

adult-onset diabetes non-insulin-dependent diabetes mellitus (NIDDM)

III. Other specific types (includes Secondary Diabetes)

IV. Gestational diabetes mellitus (GDM)American Diabetes Association: http://care.diabetesjournals.org/

IDF Atlas 2006

46.5

80.3

73%

67.0

99.4

48%10.4

18.7

80%

24.5

44.5

81%

53.2

64.1

21%28.3

40.5

43%

16.2

32.7

102%

World

2007 = 246 million

2025 = 380 million

Increase 55%Diabetes Atlas, 3rd edition, IDF 2006

Weyer C, et al. J Clin Invest. 1999;104:787-794.

Insulin resistance

Hyperinsulinemia

Compensated insulin resistanceNormal glucose tolerance

Impaired glucose tolerance

ß-cell “failure”

Type 2 diabetes

Genetic Factors

Genetic Factors

Acquired:•Obesity

•Sedentary lifestyle•Aging

ß-cell decompensation

Glucose and/or fat toxicity

DCCT Research Group.. 1993;329:977

EVERY 1% reduction in HbA1C

REDUCED RISK*

1%

Deaths from diabetes

Heart attacks

Microvascular complications

Peripheral vascular disorders

*p<0.0001Stratton IM, et al 2000

DIABETES

Periodontal Diseases- Gingivitis- Periodontitis

Oral Lichen Planus

Caries

Xerostomia

Candidiasis

• Case/Control (N=350/group)

Lalla et al 2006

From Cianciola et al JADA1982

• Experimental Gingivitis (N=9/arm)

Salvi et al 2005

From G. Taylor 1996

From Graves et al Periodontol 2000 2007

Type 2 Diabetes

Hypertension

DyslipidemiaCentral obesityInsulinResistance

TG

GlucoseDiabetes

BP

HDL

AbdominalObesity

Apo BLittle LDL PAI-1

Adipo-nectin

InsulinResistance

CRP

Microalb

Cardio- vascularDisease

Type 2Diabetes

Metabolic syndrome

• 28 Zucker rats diabetes – Ligature induced periodontitis (P) versus control (C).

• High (HF) vs Low (LF) Fat Diet

Watanabe et al 2008

Variable% or mean (95%CI)

Mild or no Periodontitis

(N=11758)

Moderate Periodontitis

(N=1582)

Severe Periodontitis

(N=337)

D’Aiuto F et al 2008

Nibali Let al 2013

• NHANES I Follow-up study (7,168 dentate) • 47% had periodontal index 0 (periodontally healthy); the

remaining periodontal index quintiles.

Demmer et al 2008

Collin et al 1998

Prospective study

Prospective study (2y) Pima Indians

Reviewed in Taylor 2008

• N=628 (>35 y) periodontal disease on CV mortality in Pima Indians with type 2 diabetes

• 11 years FU

Saremi et al 2005

• 529 individuals, – 107 (20%) none/mild – 200 (38%) moderate – 117 (22%) severe – 105 (20%) edentulous

• Up to 22 years FU

Shultis et al 2007

Janket et al 2005

Teeuw et al 2010

Updated search to 2009

Engrebretson & Kocher 2013

Variable Control (N=49) Test (N=43) P value

Age 58.48±1.64 60.02±1.69 0.515Male Gender, N (%) 34 (77,3) 28(57,1) 0.049Smoking N (%):CurrentFormerNever

13 (29,5)12 (27,3)20 (40,8)

13 (26,5) 19 (43,2) 16 (32,7)

0.369

BMI 27.31±0.55 27.50±0.79 0.853Diabetes age, years 16.50±0.90 18.04±1.67 0.558HbA1c, % 8.03±0.22 7.64±0.16 0.166SES N (%):LowMediumHigh

21 (47,7)17 (38,6)6 (13,6)

34 (69,4)13 (26,5)

2 (4,1)

0.069

Calabrese N, D’Aiuto F et al 2011

Baseline 4 Months 8 Months

HbA

1c %

0,0

7,2

7,5

7,8

8,1

8,4

TestCTRL

*=1.08%

95% CI 1.01 to 1.14, P=0.026

Calabrese N, D’Aiuto F et al 2011

Variable Control (N=10) Test (N=10)Age, years 54.99±6.67 55.44±6.64Male Gender, N (%) 6 (60) 8(80)Smoking N (%):NeverCurrent

7 (70)3 (30)

8 (80) 2(20)

BMI, Kg/m2 28±2 26±1

HbA1c, % 8.30±0.16 8.13±0.19

CRP, mg\L 4.31±0.64 3.19±1.13

WBC, 109 cell 6.24±0.61 5.42±0.40

D’Aiuto F et al Unpublished

D’Aiuto F et al Unpublished

=0.64%95%CI 0.18 to 1.26, P=0.044

D’Aiuto F et al 2005

202124 202124N =

IPTSPTControl

CRP

[mg/

L]

8

6

4

2

0

BL

2M202124 202124N =

IPTSPTControl

IL-6

[pg/

ml]

5

4

3

2

1

0

BL

2M

Periodontal Therapy - Chronic Inflammation

Correa et al 2010

• 23 T2-DM before and 3 months after non-surgical periodontal therapy.

Baseline Day 1 Day 7 1 Month 2 Months 6 Months

FM

D %

0

1

4

5

6

7

8

9

10

IPT (N=61)

CPT (N=59)

=2.0%95% CI 1.2 to 2.8,

P<0.0001

Tonetti MS, D’Aiuto F et al 2007

Periodontal Therapy - Endothelial Function

Experimental Design - RCT (N=250) UKCRN 5280

SCR

EEN

ING

BASELINE

Randomization

2m 12m1d 7d 9m6m

Test

Control

At October 2013: • N=285 recruited• N=250 reached 6 months fw-up• N=237 reached 12 months fw-up

Future goals

• Large epidemiological studies to ascertain the impact of periodontal health/diseases on diabetes incidence and complications.

• Large RCTs on Metabolic/Vascular effects of Treatment of Oral inflammation in people with Diabetes

• Mechanistic studies to clarify the pathways involved • Oral health promotion becoming part of medical

management of people with diabetes

AcknowledgementsProf John E DeanfieldDr Stefano MasiMrs Bhowruth, DevinaDr Marco OrlandiFrancis O’NeillMohamed Parkar

Eastman Clinical Investigation Centre Staff Mrs Jean SuvanNurses (Banbai Hirani, Kasia Niziolek, Tiffany Mellor) Dental hygienists (Alastair Lomax, Chiara Curra’)Heather FinchProf Nikos DonosDr Nikolaos Gkranias

Prof Aroon D Hingorani, UCLProf Liam Smeeth, LSHTMProf Raymond MacAllister, UCLProf Derek Yellon, UCLDr Derek Housenloy, UCLProf Steve E Humphries, UCLDr George Tsakos, UCL

Research Group Collaborators - UK

Collaborators - EUProf Pirkko Pussinen, HelsinkiProf Ulf Landmesser, Zurich