This proposal describes a population-based incident cohort study of young individuals with Type 1 diabetes designed to determine risk factors for the initiation and early progression of atherosclerotic vascular disease (ASVD). Individuals with Type 1 diabetes have substantially higher risk for premature ASVD than the general population. Risk factors for the development of ASVD have been identified, but linking them to initiation of atherosclerosis was not feasible until recently. Advances in non-invasive imaging now permit early detection of changes in blood vessel function and structure. This imaging provides an opportunity to evaluate risk factors for ASVD and vascular status in a cohort at a critical time for development and early progression of ASVD. Participation of the cohort is excellent. Subjects were enrolled from 1987-1992 and have been followed from diabetes diagnosis. Standardized protocols for examinations and interviews have been implemented and the data base includes a valuable longitudinal plasma bank. Because we enrolled incident cases, we have collected information from diagnosis on children, adolescents and young adults currently without symptoms of atherosclerosis. We propose to expand our existing database, to use our existing resources including our plasma bank, and to incorporate promising new and well established clinical research techniques by: (i) measuring plasma lipid levels on stored plasma and on newly collected blood samples, (ii) measuring triglyceride levels on newly collected blood samples, (iii) measuring urinary albumin excretion rates on newly collected specimens (already measured from diagnosis to date), and (iv) assessing endothelial function by brachial artery ultrasound, (v) measuring the intima medial thickness (IMT) of the carotid artery by ultrasound, and (vi) measuring coronary calcium by computed tomography scanning. These activities will allow us to pursue the following specific aims: 1) to determine the relationship between established risk factors for atherosclerosis and the development of pre-clinical atherosclerosis, 2) to determine the relationship between endothelial dysfunction and carotid IMT, and 3) to determine the relationship between coronary artery calcification and carotid IMT. Such information is critical in directing further efforts toward primary prevention of atherosclerosis in individuals with Type 1 diabetes mellitus.
