PERIODONTAL DISEASE AND THE RISK OF PRE-DIABETES AND TYPE 2 DIABETES
Mustapha, Indra Zena
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Periodontal disease is a known risk factor for diabetes in the dental literature, where most studies were cross-sectional in design and include individuals with normoglycemia and those with pre-diabetes in the same comparison groups. Despite the discussion of a bi-directional relationship for the past twenty years, evidence to support the effect of periodontal disease on the risk of incident diabetes is lacking. This dissertation explored the increased risk of insulin resistance and diabetes in response to oral inflammation. We hypothesized that oral inflammation increases the risk of insulin resistance and diabetes. This thesis consisted of three aims to test this overall hypothesis. The first aim used cross-sectional data from the 6, 138 individuals in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort. Compared to individuals in Category I (probing depth (PD) <3mm and bleeding upon probing (BOP) ≤10%), the odds ratio for impaired fasting glucose in those with severe periodontal inflammation (Category V- one or more sites with a PD ≥4mm and BOP ≥50) was 1.5 (95%CI:1.1-2.1). A modest association between serum antibody levels to periodontal pathogens (Porphyromonas gingivalis and Actinobacillus actinmycetemcommitans) and gingival crevicular fluid levels of IL-1β and PG-E2 and pre-diabetes status was suggested but did not reach statistical significance. The second aim used the same population, where of the total 5,819 eligible participants at baseline (ARIC Visit 4), ¬1,967¬¬ individuals developed incident type 2 diabetes after a mean of 13.8 years of follow-up. Incident diabetes was assessed with yearly telephone interviews and self-reports from study participants. In multivariable analyses using the Cox proportional hazards model, when compared to Category I (probing depth (PD) ≤3mm, bleeding upon probing ≤10%), the hazard ratio of incident diabetes was the highest with early periodontal clinical measures of inflammation as found in Category II (probing depth (PD) ≤3mm, bleeding upon probing >10%) (HR=1.4, 95%CI: 1.1-1.7,p<0.001) after adjustment for sex, age, race, education level, smoking status, physical activity, total caloric intake, waist circumference, hypertension, previous cardiovascular disease, family history of diabetes, and HDL cholesterol levels. Compared with individuals in Category I, with minimal bleeding and probing measures, the hazard of incident diabetes appears to be 1.2 times higher (95% CI: 1.0 – 1.4, p<0.001) in adults with moderate clinical periodontal inflammation (Category IV-one or more sites with PD≥4mm, bleeding upon probing >10% &<50%) and 1.3 times higher (95% CI: 1.0- 1.6, P<0.001) in adults with advanced clinical periodontal inflammation (Category V- one or more sites with PD≥4mm, bleeding upon probing ≥50%). The third aim was a survey of 100 Washington DC area Periodontists, to assess the attitudes and beliefs of these specialists towards the relationship of periodontal inflammation and the risk of diabetes, and how these beliefs influenced the standard of care in treating dental patients. This survey (respondents n=39) found that practicing periodontists were aware of the association between periodontal disease and onset of type 2 diabetes (92.9%agreed/ strongly agreed). These respondents appeared to be aware of the importance of HbA1c testing in assessing glycemic control, whether this test was performed in the dental office or medical setting. The results of this dissertation demonstrated that clinical periodontal inflammation was associated with an increased risk of pre-diabetes and subsequent incident diabetes. In addition, local periodontists understood the importance of the relationship between diabetes and periodontal disease in treating periodontal patients in clinical practice. Interventional studies are needed in the future to test whether prevention of the onset of periodontal inflammation reduces pre-diabetes and incident diabetes.