DOES PERIODONTAL INFLAMMATION AFFECT GLYCOSYLATED HEMOGLOBIN LEVEL IN OTHERWISE SYSTEMICALLY HEALTHY INDIVIDUALS?-A HOSPITAL BASED STUDY

summary Periodontal disease isa common, chronic, complex multifactorial disease characterized by destruction andloss of connective tissue attachment. The mostprevalent form is chronic periodontitis. There is increasingevidence that microbial biofilm and host susceptibility plays an important rolein initiation and progression of periodontitis1.Recent studies have demonstrated that chronic periodontitis is a potential riskfactor for systemic diseases like coronary heart diseases/atherosclerosis, worseningglycemic control in diabetes mellitus, adverse pregnancy outcome etc2.Periodontal disease has now be recognized as the sixth complication of diabetes3.Diabetes mellitus is a common multifactorial disease process involving genetic,environmental and behavioral risk factors affecting up to 5% of the generalpopulation of world4.India leads the world with largest number of diabetic subjects to around 40.9million5.In Kerala, Kutty et. al reported 16.3 percent crude prevalence of diabetesmellitus among adults aged 20 years or above in an urban settlement6.

Numerous epidemiologic surveys demonstratedthat there is an increased prevalence of periodontitis among patients withuncontrolled or poorly controlled diabetes mellitus7.Evidence has consistently indicated that diabetes is a risk factor forincreased severity of gingivitis and periodontitis8. Conversely,periodontitis may be a risk factor for worsening glycemic control. Althoughthe biologic mechanisms linking periodontitis to impaired glucose metabolismhave not been fully elucidated.  Inflammatorymediators(particularly interleukin-1, interleukin-6 and tumor necrosis factor-alpha)generated within the inflamed periodontal tissues translocate into the systemiccirculation and interfere with the actions of insulin receptors, therebydecreasing insulin sensitivity associated with degree of glycemic control of diabetes9. These inflammatory mediators  (IL-1), IL-6,(TNF-α) and prostaglandinE2 (PGE2) can interact systemically with lipids, freefatty acids and advanced glycation end products (AGES). This interactioninduces or perpetuates activation of the intracellular pathways, such as theI-kappa-B (IκB), I-kappa-B kinase-β (IKKβ), nuclearfactor-kappa B (NF-kβ) and the protein c-Jun N-terminalkinase (JNK) axes. The activation of these inflammatory pathways in immunecells (monocytes or macrophages), endothelium cells, adipocytes, hepatocytesand muscle cells promotes and contributes  to an increase in the overall insulinresistance, which makes itdifficult to achieve metabolic control in patients with both type 2 diabetesand periodontitis10 .In 2010 American Diabetes Association Standardsof Medical care in Diabetes added the A1c ≥ 48 mmol/mol (≥6.5%) as anothercriterion for the diagnosis of diabetes11**.** People without diabetes usually have a level of 4.5% - 6%.So,in between....6.0-6.5...may be ’pre-diabetes’ or ’at risk of diabetes’. (WHO2010)

 Although many studies reported more severeperiodontal disease in subjects with diabetes than those without diabetes, relativelyvery few examined the association between periodontitis and glycemia or thelevel of glycosylated hemoglobinin in adults without diabetes12.  Saito et al.13 found that alveolar boneloss was associated with impaired glucose tolerance in Japanese men withoutdiabetes. Similarly Nibali et al.14 found slightly, butstatistically significantly, higher non-fasting glucose levels in periodontitiscases compared to healthy controls. These studies suggest that periodontitismay affect glucose metabolism in the general population, albeit to a lesserextent than in adults with diabetes.

So we hypothesized that patients with periodontitis have higher HbA1clevels than healthy patients and the purpose of this study is to examine theassociation between periodontitis and HbA1c level in otherwise systemicallyhealthy individuals.

 AIM

Toidentify a possible association between chronic periodontitis and glycosylatedhemoglobin levels in otherwise systemically healthy individuals.

OBJECTIVES

1.      Toassess glycosylated hemoglobin levels in otherwise systemically healthyindividuals with chronic periodontitis and compare it with a healthy controlgroup.

2.      Tocorrelate the level of inflammatory marker like serum albumin and CRP withperiodontal parameters.

METHODOLOGY

Study design

Crossectional(observational) study

 MATERIALS AND METHODS

Study population andsample size: Subjects in this study group tocomprise of 100 patients.   Thesesubjects will be divided in to two groups.

1.      Cases: (Group I) casesincludes total of 50 subjects otherwise systemically healthy patients withchronic periodontitis reporting to the department of periodontics GOVT DENTALCOLLEGE CALICUT.

2.      Control:****(Group II) includes 50 subjectsotherwise systemically healthy without chronic periodontitis. Control shouldmatch for age, sex, and to cases. These subjects will undergo general, oral orperiodontal examination and laboratory investigations.

 Duration of the study

18months.

Study setting

LocationThis study is to be conducted by the department of Periodontics, GOVT. DENTALCOLLEGE CALICUT in collaboration with department of biochemistry GOVT MEDICALCOLLEGE CALICUT.

 INCLUSION CRITERIA FORCASE GROUP

1.Patients with age group between 25 to 55.

2.Minimum of 20 teeth present.

3.Patients who were diagnosed with severeperiodontitis chronic periodontitis (CDC criteria   moderate periodontitis is defind as ≥2interproximal sites with  ≥ 4mm clinicalattacment loss (CAL) not on same tooth,or ≥2 interproximal with probing depth(PD) ≥ 5mm not on same tooth severe periodontitis is defind as ≥2 teeth withclinical attachment loss  ≥6mm not onsame tooth and  ≥1 interproximal sitewith probing depth  â‰¥ 5mm).

5.Nofamily history of Diabetes,

     INCLUSION CRITERIA FORCONTROL GROUP

1.      Healthyindividuals with age group between 25 to 55.

2.      Minimumof 20 teeth present.

3.      Subjectswho do not fall within the diagnostic criteria for moderate or severe periodontitis(CDC criteria)

4.      Nofamily history of Diabetes

EXCLUSION CRITERIA

1.      Patientswith known systemic disease and condition such as CVD, renal disease, RA,diabetes Mellitus, liver and pancreatic disease, nutritional deficiencies,pregnant and lactating mother.

2.  Patients with conditions that shortenerythrocyte survival (e.g., hemolytic anemia, pregnancy, or recent  significant blood loss, or who are positivefor rheumatoid factors.)

3.  Patientswith acute condition that contraindicate a periodontal examination.

4.  Patientswho received systemic antibiotic therapy within past 6 month.

5.  Patientswho received periodontal therapy (scaling and root planing or surgery) past 1year.

6.  Patientsnot willing to sign informed consent.

             ARMAMENTARIUM

1.      Mouthmirror

2.      Explorer

3.      Williamsgraduated periodontal probe

4.      Disclosingagents

5.      HbA1cassessment kit

6.      CRPassessment kit

DATACOLLECTION

DataCollection Tools

1.      Questionnaire

2.      Clinicalexamination

3.      Blood  investigation

 Periodontal Parameters

1.      Probingdepth

2.      Clinicalattachment level

3.      Gingivalrecession

4.      Simlifiedoral hygiene index

5.      Plaqueindex

6.      Modifiedgingival index

SystemicParameters

1.      TCH

2.      HDL

3.      LDL

4.       VLDL

5.      TRIGLYCERIDES

6.       BLOOD GLUCOSE (fasting and post prandial)

7.      BP

8.      BMI

9.      WHR

10.   GLYCOSYLATED HEMOGLOBIN

11.  CRP

12.  SERUMALBUMIN

INFORMEDCONSENT

Awritten informed consent will be obtained from all participants in the study .Demographicdata includes age, gender, weight, educational level, ethnicity, occupation, familyincome . Complete medical history includes diabetic history, history of CVD andhypertension, medication etc. The laboratory assays include, BMI, WHR, CRP, fastingblood sugar, total cholesterol, HDL, LDL, Triglycerides etc.

DATA ANALYSIS

(α value will be set at 5% and β value will beset at 80%)

QualitativeData by chi-square test

QuantitativeData by student ‘t’ test

Oddsratio & correlation coefficient

Multivariatelinear regression

FUNDING      -Rs60000/-

ANNEXURE

1.      PROFORMA

2.      CONSENT

      REFERENCES

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2. Lindhe J, Karring T, Lang NP. Clinical periodontology and implant dentistry. Oxford ; Malden,Mass.: Blackwell Munksgaard; 2003: xxiv, 1044 p.

3. Loe H. Periodontal disease the sixth complication ofdiabetes mellitus. Diabetes Care1993;16:329-334.

4. King H, Aubert RE, Herman WH. Global burden of diabetes,1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-1431

5. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C.Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007;125:217-230.

6.  Raman Kutty V,Joseph A, CR S. High prevalence of type 2 diabetes in an urban settlement inKerala, India. Ethn Health 1999;4.

7. Taylor GW. Bidirectional interrelationships betweendiabetes and periodontal diseases: an                 epidemiologic perspective. Ann Periodontol 2001;6:99-112.

8.  Mealey BL, Oates TW.Diabetes mellitus and periodontal diseases. *J Periodontol.*2006;77:1289-303.

9. Mealey BL,Ocampo GL. Diabetes mellitus and periodontal disease. Periodontol 20002007;44:127-153.

10.Roberta Santos Tunes.Impact of Periodontitis on theDiabetes-Related Inflammatory Status.: J      Can Dent Assoc2010;76:a35

11.Standards of medical care in diabetes Care 33(Suppl1) S4– 10 January 2010.

12.  Ryan E. Wolff,* Larry F. Wolff,† and Bryan S.Michalowicz. Pilot Study ofGlycosylated Hemoglobin Hemoglobin Levels in Periodontitis Cases and HealthyControls( J Periodontol 2009;80:1057-1061)

13.  Saito T,Murakami M, Shimazaki Y, Matsumoto S, Yamashita Y. The extent of alveolar boneloss is associated with impaired glucose tolerance in Japanese men. JPeriodontol 2006;77:392-397.

14.  Nibali L,D’Aiuto F, Griffiths G, Patel K, Suvan J,Tonetti MS. Severe periodontitis isassociated    with systemic inflammationand a dysmetabolic status: A case-control study. J Clin Periodontol2007;34:931-937.