This project continues to explore the contribution of altered cholesterol me@abolism to the accelerated atherosclerosis of diabetes. We are studying a) the effect of diabetic control on cholesterol synthesis as determined by sterol balance and by the method of squalene kinetics; b) the effect of diabetes, ketosis and insulin on the rate-limiting enzyme in cholesterol synthesis HMG-CoA reductase; and c) the effect of diabetes on non-sterol pathways of mevalonic acid metabolism. The overall purpose of the study is to improve our understanding of how diabetes affects cholesterol metabolism, and how insulin treatment modifies these effects.