Metabolism and vascular function in prior Gestational Diabetes

Research project P 14515 Metabolism and voscular function in prior Cestational Diabetes A. KAUTZKY-WILLER 09.10.2000 Although most women with gestational diabetes mellitus (GDM) return to normal glucose tolerance after delivery, it is well established that glucose intolerance detected during pregnancy is predictive of later maternal Type II Diabetes (approx. 50% in 5 years). GDM is characterized by insulin resistance and impaired insulin secretion, which only partially normalize after delivery. Subjects at high risk for type 11 diabetes like women with previous GDM can show vascular dysfunctions and early signs of atherosclerosis before the onset of diabetes and only slight elevations in fasting and postprandial glucose have been shown to be associated with macrovascular complications. It is of special interest that women have a significantly greater cardiovascular risk (x 20) than men when plasma glucose is increased. This study therefore intends to investigate glucose tolerance, insulin and P-cell-sensitivity and P-cell activity (insulin, proinsulin, islet amyloid polypeptide release) by minimal modeling from oral and intravenous glucose tolerance tests in relation to vascular function in women with a history of GDM (from 6 weeks after delivery to 5 years postpartum). Earlysigns of atherosclerosis will be evaluated by intima-iriedia4finickness (IN4T) measurements of carotid `artery by ultrasound. Vascular function will further be described by measurement of plasmatic parameters such as adhesion molecules, L-arginine (dimethylarginine:ADN4A, SADMA), TNF a, PAM, vWillebrandt factor and fibrinogen. In addition, forearm blood flow and vascular reagibility of the brachial artery during reactive hyperemia (endothelium-dependent vasodilation) and in response to pharmacologic stimulation will be measured in a subgroup of patients during follow-up. Lifestyle (physical activity, diet) will be evaluated by spiroergometry and analysis of standardized questionnaires and diet records, respectively. Type II Diabetes is an increasing general health problem in westernized civilisation. Diabetic women have been shown to have a significantly greater cardiovascular risk than diabetic men. Women with a history of GDM at risk for Type Il Diabetes represent the unique possibility to study the natural course of Type 11 Diabetes, to define risk factors for progession of glucose intolerance and to establish primary prevention settings. This prospective longitudinal study will relate glucose metabolism to vascular function in women with a history of GDM at risk for Type 11 Diabetes and study risk factors associated with progression to Type 11 Diabetes amd atherosclerosis.