Caffeine has widespread effects in the 90 percent of US adults who consume it daily. Recent research in our laboratory indicates that caffeine has disruptive effects on glucose metabolism that may seriously impair glycemic control in type 2 diabetes and aggravate insulin resistance in pre-diabetic individuals. We propose 4 studies to determine the nature and extent of caffeine's effects and their potential importance to diabetes. A replication and extension of our preliminary study will examine the effects of a controlled dose of caffeine on fasting glucose and insulin and responses to the oral glucose tolerance test (OGTT) to determine whether caffeine aggravates hyperglycemic and hyperinsulinemic responses in type 2 diabetes patients. We will test a variety of clinical and physiological factors that could account for individual differences in caffeine's effects, to identify patients at greatest risk of impairment and to elucidate potential mechanisms of action. A similar study will determine caffeine's effects on glucose metabolism in subjects who are currently "pre-diabetic," but at risk of developing clinical diabetes. Confirming that caffeine increases insulin resistance and may elicit hyperglycemia in this group would establish caffeine as a factor that could aggravate and contribute to the metabolic processes that lead to the development of diabetes in this high-risk group. A third study will extend our laboratory findings into the natural environment and explore the use of continuous glucose monitoring system (CGMS) methodologies to determine the effects of caffeine consumption on blood glucose during normal daily activities. These ambulatory measurements will complement the controlled laboratory studies and establish the ecological importance of these effects. Together these studies will establish a foundation of evidence regarding caffeine's effects on glucose metabolism and their importance to clinical glucose management in type 2 diabetes. This foundation will support later studies of mechanism as well as clinical intervention trials.