EXERCISE AND GLUCOSE HOMEOSTASIS IN GESTATIONAL DIABETES

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Gestational diabetes (GDM) results in perinatal morbidity and mortality due, in part, to fetal hyperinsulemic response to maternal hyperglycemia. The metabolic defect(s) producing maternal hyperglycemia has not been conclusively identified, but may include both abnormalities in insulin release and reduced insulin sensitivity. Furthermore, present management of GDM requires costly surveillance of all GDM and insulin therapy in up to 50% of cases, yet does not eliminate the risks of fetal macrosomia, operative delivery and neonatal morbidity characteristic of this disorder. Physical exercise increases insulin sensitivity and improves glucose control in nonpregnant patients with NIDDM and offers a potentially cost effective tool for reducing GDM related morbidity. No studies during pregnancy, however, have examined the effect of physical training on insulin action. We plan to extend our studies of the acute and chronic exercise during pregnancy to resolve these questions and to examine the potential impact of physical exercise on metabolic control in GDM. First, the role of abnormal insulin release in GDM will be examined by use of the hyperglycemic clamp in a cohort of parous subjects with (n=30) or without (n=12) prior gestational diabetes. These women will be enrolled prior to conception, and the effect of pregnancy on insulin release and sensitivity, and the role of these changes in the pathogenesis of GDM will be examined. Subjects in this cohort who develop GDM will be randomized to a 6 week trial of exercise training and non-exercise, and the effect of this trial on early phase insulin release and sensitivity will be quantified. A second protocol will examine the differential effects of an isolated exercise session versus chronic exercise training on peripheral insulin sensitivity and supressability of endogenous glucose production using the euglycemic clamp. Subjects for the second protocol will include lean (20) and obese (20) non-diabetic and gestational diabetic (20) pregnant women who will be randomize to a 6 week training/sedentary trial. These protocols should define the mechanism by which physical training may improve glycemic control in GDM, and quantify this effect to evaluate the therapeutic potential of exercise in managing this disorder.