Caffeine and Glucose Regulation

描述（由申请人提供）：咖啡因对90%的美国成年人有广泛的影响，他们每天都摄入咖啡因。我们实验室最近的研究表明，咖啡因对葡萄糖代谢具有破坏性影响，可能严重损害2型糖尿病患者的血糖控制，并加重糖尿病前期患者的胰岛素抵抗。我们提出了4项研究来确定咖啡因影响的性质和程度以及它们对糖尿病的潜在重要性。我们的初步研究的复制和扩展将检查控制剂量的咖啡因对空腹血糖和胰岛素的影响，以及对口服葡萄糖耐量试验（OGTT）的反应，以确定咖啡因是否会加重2型糖尿病患者的高血糖和高胰岛素反应。我们将测试多种临床和生理因素，这些因素可以解释咖啡因影响的个体差异，以确定最容易受损的患者，并阐明潜在的作用机制。

DESCRIPTION (provided by applicant): 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.