Recent research in our laboratory has provided evidence that the metabolic correlates of hostility may play a role in the racial disparity in the prevalence of type 2 diabetes. We propose to study how hostility is differentially related to glucose metabolism in healthy African-Americans and Caucasians, to determine the underlying behavioral and physiologic mechanisms of these relationships, and to investigate the possibility that race and sex interact in determining this relationship. We will assess the multi-factorial nature of hostility in 400 healthy African-American and Caucasian men and women. These psychometric measures will be examined in relation to fasting and two-hour post-prandial glucose and insulin as well as hemoglobin AIC (HbAIC) on all subjects. We will test the hypothesis that hostility is related to insulin resistance in Caucasians and to glucose production and defective glucose-stimulated insulin secretion in African-Americans, putting hostile African-Americans at greater risk for developing diabetes. Accordingly, we will assess glucose-stimulated insulin release, insulin resistance, hepatic glucose production and glucose effectiveness utilizing an IV GTT with labeled glucose in a subset of our sample. We will begin to determine the mechanism by which hostility impacts glucose metabolism in an African-American and Caucasian population. Three sets of mediators will be examined in the subjects studied parameters of hypothalamic-pituitary-adrenal (HPA) axis activity, measures of body mass and fat distribution, and measures of behavioral factors including calorie intake and exercise habits. It is further hypothesized that while the relationship of hostility to fasting insulin and insulin sensitivity in Caucasians is mediated by BMI and behavioral variables, the relationship of hostility to fasting glucose in African-Americans will depend on neuroendocrine factors influencing hepatic glucose production and insulin secretion. These studies will further our understanding of the differences in the etiology of diabetes in these ethnic groups and may help explain the racial disparity in this disease.