Several studies have shown associations between periodontal disease and type 2 diabetes, but very little evidence is available from longitudinal studies. Hence, the relationships are complex and it is unclear whether periodontal disease is a cause or consequence of diabetes or both and it is important to establish the temporal sequence. As a first step to clearly establish the time sequence, this study focuses on assessing the impact of periodontal disease on the progression of preclinical stages of diabetes and the impact of preclinical stages of diabetes on progression of periodontal disease. This study is unique in establishing a cohort of overweight and obese individuals free of diabetes. This unique population will constitute a high risk group because of the high levels of periodontal disease and insulin resistance and expected higher rates of progression enabling an efficient design. The specific aims are: (1) to assess whether, over a three-year period, individuals with periodontal disease at baseline have a higher increase in glucose intolerance and insulin resistance compared to those without periodontal disease; (2) to determine if the longitudinal association between baseline periodontal disease and increases in glucose tolerance and insulin resistance is mediated through adipokines, dyslipidemia and/or inflammatory markers, including C reactive protein, tumor necrosis factor , and interleukin 6; (3) to assess whether baseline glucose abnormalities and insulin resistance are associated with progression of periodontal disease over a three-year interval; and (4) to assess the linear association between adiposity measures including body mass index, waist circumference and fat mass at baseline and periodontal disease. We plan to include a high-risk group of overweight or obese adults, 40-65 years of age, free of diabetes and of conditions that preclude a periodontal exam recruited from the San Juan municipality. Participants will be assessed at baseline and three years after the baseline exam. The baseline and follow-up visits will include blood drawing at fasting and 2 hour oral glucose tolerance test, blood pressure assessment, dental examinations, interviews and anthropometrics measures. We will evaluate the longitudinal relationship between clinical periodontal measures and changes over a three-year time period in oral glucose tolerance and insulin resistance. We will also assess the relationship of baseline anthropometric measurements, oral glucose and insulin resistance with the progression of periodontal disease. The long-term goals will be to continue follow-up to assess whether periodontal disease is a risk factor for the incidence of type 2 diabetes among participants with glucose intolerance and/or insulin resistance. Given the high prevalence of periodontal disease and type 2 diabetes, this study is highly significant as periodontal disease could be a modifiable risk factor for type 2 diabetes. PUBLIC HEALTH RELEVANCE: Given the high prevalence of periodontal disease and insulin resistance, this study will play a key role in determining whether periodontal disease could potentially be a modifiable risk factor for insulin resistance which could have implications in the prevention of type 2 diabetes. Measures that prevent diabetes or periodontal disease or measures that improve glucose homeostasis are central to reducing morbidity and mortality as well as to reducing the growing problem of health care disparities for diabetes, especially among minority, low-income, and underserved adult populations.