This is an ongoing observational study designed to identify potential causes of type 2 diabetes mellitus at the physiological level in relatively young, high-risk Hispanic women. Subjects have been scheduled for detailed metabolic characterization at 15-month intervals after an index pregnancy complicated by gestational diabetes mellitus. Follow-up continues until they develop hyperglycemia requiring clinical intervention. Analyses of results to 75 months postpartum suggest that type 2 diabetes develops as a 3- step process: (a) insulin resistance places high insulin secretory demands on pancreatic beta-cells; (b) there is a progressive loss of beta-cell function that is related at least in part to the high secretory demands imposed by insulin resistance; and (c) glucose levels rise slowly across a wide range of falling beta-cell function, and then much more rapidly and to diabetic levels when beta-cell function falls below about 10% of normal. The present application proposes additional follow-up, measurements and analyses of the cohort to: (a) define patterns of change in glucose levels across a longer period of time and a wider range of changing beta-cell function; (b) identify predictors and potential determinants of falling beta-cell function during long-term follow-up; and (c) explore the potential role of adipokines in the generation of insulin resistance, beta-cell dysfunction and diabetes. The results will provide unique, longitudinal information about potential physiological and hormonal mechanisms for type 2 diabetes in relatively young Hispanic women. The information will be important for the design of strategies to identify high-risk individuals and reduce their risk of type 2 diabetes.
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