Diabetes Research in Children Network (DirecNet)

描述(由申请人提供)：第1节总结了研究人员和机构(WUMS)在智力和操作上积极参与与本网络将进行的预防胰岛素治疗糖尿病受试者低血糖的研究相关的方案制定、实施、数据分析和结果传播的资格。第2节将概述一项具体提案，供该网络审议。本文提出的具体建议题为“睡前p2-肾上腺素能激动剂疗法预防1型糖尿病儿童低血糖”。我们的建议是基于与低血糖相关自主神经衰竭(HAAF)及其相关成分(葡萄糖逆调节缺陷、无意识低血糖、运动相关的HAAF、睡眠相关的HAAF)及其与低血糖风险的关系的研究，以及我们的初步研究表明，p2肾上腺素能激动剂特布他林可以降低胰岛素治疗的1型糖尿病受试者的夜间低血糖。在此，我们提出了初步的初步研究，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影响。然后，我们建议利用这些先导性研究的结果和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，以确定特布他林是否能够将睡前低血糖降低到能够改善总体血糖控制的程度。我们还建议对低血糖和高血糖对认知功能的风险进行探索性研究。在实现和维持糖尿病长期微血管、大血管和神经病变并发症的减少所必需的水平上建立最佳的血糖控制受到低血糖风险的限制。预防低血糖的战略将有助于更好地全面控制血糖，这将是需要胰岛素的糖尿病管理方面的一项重要进展。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.