Diabetes Research in Children Network (DirecNet)

描述（由申请人提供）：第1部分总结了研究者和机构（WUMS）积极参与方案制定、实施、数据分析和传播相关研究结果的资格，这些研究将由本网络开展，用于预防胰岛素治疗糖尿病受试者的低血糖。第2节将概述一项供网络审议的具体建议。本文提出的具体建议题为“睡前p2-肾上腺素能激动剂治疗预防1型糖尿病儿童低血糖”。我们的建议是基于研究，包括我们自己的小组和其他研究者的研究，与低血糖相关的自主神经衰竭（HAAF）及其相关成分（葡萄糖反调节缺陷，低血糖无意识，运动相关的HAAF，睡眠相关的HAAF）及其与低血糖风险的关系，以及我们的初步研究表明p2-肾上腺素能激动剂特布他林，减少胰岛素治疗的1型糖尿病患者夜间低血糖。在此，我们提出初步的试点研究，以确定特布他林安全预防夜间低血糖的最佳剂量，并探讨特布他林对夜间低血糖、低血糖反调节和睡眠效率的生理作用。然后，我们建议利用这些试点研究的结果以及通过该网络建立的合作来开发和实施一项大型、多中心、随机、双盲、安慰剂对照的临床试验，以确定睡前特布他林是否能将低血糖降低到能够改善整体血糖控制的程度。我们还建议探索性研究低血糖和高血糖对认知功能的影响。为实现和维持糖尿病微血管、大血管和神经性并发症的长期减少所必需的最佳血糖控制水平受到低血糖风险的限制。预防低血糖的策略能够更好地全面控制血糖，这是胰岛素依赖型糖尿病治疗的重要进展。该研究网络将开发和评估预防低血糖和改善糖尿病控制的策略。

DESCRIPTION (provided by applicant): Section 1 summarizes the qualifications of the investigators and institution (WUMS) to actively participate intellectually and operationally in protocol development, implementation, analysis of data and dissemination of results related to studies to be conducted by this Network for the prevention of hypoglycemia in insulin-treated diabetic subjects. Section 2 will outline a specific proposal for consideration by the Network. The specific proposal presented herein is entitled "Bedtime p2-adrenergic agonist therapy to prevent hypoglycemia in children with type 1 diabetes". Our proposal is based on studies, including those from our own group and other investigators, related to hypoglycemia-associated autonomic failure (HAAF) and its related components (defective glucose counterregulation, hypoglycemia unawareness, exercise-related HAAF, sleep-related HAAF) and thier association with the risk of hypoglycemia, and our preliminary studies suggesting that the p2-adrenergic agonist, terbutaline, diminishes nocturnal hypoglycemia in insulin-treated type 1 diabetic subjects. Herein, we propose initial pilot studies to determine the best dosage of terbutaline for the safe prevention of nocturnal hypoglycemia and to explore the physiologic effects of terbutaline on nocturnal hypoglycemia, hypoglycemia counterregulation and sleep efficiency. We then propose to use the results of these pilot studies and the collaborations established through this Network to develop and implement a large, multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether bedtime terbutaline reduces hypoglycemia to a degree that enables improvement of overall glycemic control. We also propose exploratory studies of the risks of hypo- and hyperglycemia on cognitive function. Establishing optimal glycemic control at the level necessary to achieve and maintain reduction of long term microvascular, macrovascular and neuropathic complications of diabetes has been limited by the risk of hypoglycemia. Strategies to prevent hypoglycemia that would enable better overall glycemic control would represent an important advance in the management of insulin-requiring diabetes mellitus. This research Network will develop and evaluate strategies to prevent hypoglycemia and improve diabetes control.