The candidate's immediate goal is to continue his transition toward a fully independent investigator status with emphasis of the field of brain metabolism in diabetic man. The overall goal of these studies is to provide a more through understanding of the critical role the brain plays in regulating systemic glucose metabolism in patients with diabetes. The central nervous system is almost completely dependent upon a constant supply of glucose from the circulation in order to function normally. Yet, brain tissues are able to make and store only a few minutes-worth of glucose for periods when the body's supply to the brain is interrupted (i.e., hypoglycemia). A major goal of the proposed investigations is to better define the role which the central nervous system plays in preventing and reacting to changes in systemic glucose concentration (either hyper- or hypoglycemia) in man. The relevance of these investigation is underscored by experience with the Diabetes Control and Complications Trial, which has discovered a greatly increased risk of severe hypoglycemia in patients attempting to fully normalize their glycemic control. If intensive insulin therapy is found to prevent complications of diabetes, then more effective treatment strategies will need to be defined in order to reduce the overall risk of hypoglycemia. Such a task would be greatly facilitated by a better understanding of changes in central nervous system glucose metabolism that may occur in association with the diabetic state. Other aspects of brain energy metabolism in the setting diabetes in man.will be examined including the direct roles that insulin and epinephrine may play in determining rates of brain glucose utilization. Finally, the contributing role that the brain may play in disposing of consumed glucose in health and in the diabetic state will be compared. The investigations described rely upon the direct measurement of brain glucose utilization in man by the cross-brain glucose balance technique originally developed by Kety and Schmidt. The technique is a highly reliable quantification of cerebral blood flow coupled with measurement of cross-brain glucose extraction.