In Subproject 4, The Role of Thrombosis in Macrovascular Disease in IDDM, John Colwell as subproject principal investigator, investigates abnormalities in hemostasis as contributors to the excess cardiovascular morbidity and mortality associated with diabetes mellitus. Each of 200 EDIC patient enrolled in the study and non-diabetic, control subjects are assessed for endogenous fibrinolysis and are evaluated for prothrombin activation fragment F1+2 as an index of thrombin generation and fibrinogen and hematocrit as basic hemorheologic parameters. The studies are conducted cross-sectionally in the total EDIC cohort, and longitudinally in selected EDIC patients whose diabetes either has not progressed or has progressed to microalbuminuria or macrovascular disease. Hemostasis parameters are correlated with other metabolic characteristics measured in the program project grant and with PAI-1 and fibrinogen gene polymorphism.