In this program project grant, three of five subprojects are epidemiological studies. In the first subproject, Glycoxidation and Macrovascular Disease in Diabetes, Timothy J. Lyons, subproject principal investigator, investigates the mechanisms underlying accelerated atherosclerosis in diabetes, specifically, the modification of lipids, proteins, and carbohydrates by interrelated oxidation and glycation (glycoxidation). The cross-sectional and longitudinal study uses approximately 900 Type 1 diabetic patients from the Epidemiology of Diabetes Intervention and Complications Study (EDIC), a multicenter study which follows patients from the Diabetes Control and Complications Trial (DCCT), both of which were supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Cross-sectional studies are performed for a detailed analysis of potentially atherogenic low density lipoproteins and triglyceride-rich lipoproteins in patients with and without microalbuminuria and macrovascular disease. In a smaller cohort of the same patients, categorized as prone or resistant to macrovascular disease, levels of glycation and oxidation products are determined in insoluble skin collagen, a long-lived protein in which modifications may reflect integrated glycoxidation over many years. In the longitudinal arm of the study, characterizations of lipoproteins in selected patients are repeated in selected patients who progress either to microalbuminuria or macrovascular disease. By combining cross-sectional and longitudinal information, the investigators hope to identify new markers to identify diabetic patients at particular risk of disease progression.