A proposed model linking inflammation to obesity, diabetes, and periodontal infections

Background: Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFa) and its soluble receptors (sTNF alpha) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections. Methods: The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNF alpha and sTNF alpha were assessed in subsets of 1,221 adults from Erie County, New York, who represented the highest and lowest quartile of BMI. These subjects had extensive periodontal and medical evaluations. Results: In the NHANES III portion of the study, BMI was positively related to severity of periodontal attachment loss (P < 0.001). Weighted multiple logistic regressions showed that this relationship is likely mediated by insulin resistance, since overweight individuals (with BMI >= 27 kg/m(2)) with high levels of insulin resistance (IR) exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe periodontal disease as compared to overweight subjects with low IR. In the Erie County adult population, the highest levels of TNFa, and sTNF alpha receptors were found in those individuals in the highest quartile of BMI. A positive correlation of TNF alpha levels with periodontal disease was found only in those in the lowest quartile of BMI. Conclusions: Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNF alpha and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.