Diabetes Research in Children Network (DirecNet)

儿童糖尿病研究网络 (DirecNet)

• 批准号: 7932053
• 负责人: Neil H. White
• 金额: $ 33.5万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932053
• 关键词: Address; Adolescent; Adrenergic Agonists; Age; Asthma; Bronchodilator Agents; Child; Clinical Trials; Collaborations; Complications of Diabetes Mellitus; Controlled Clinical Trials; Data; Data Analyses; Diabetes Mellitus; Dose; Double-Blind Method; Exercise; Failure; Glucose; Hormones; Hyperglycemia; Hypoglycemia; Incidence; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Investigational Drugs; Neurocognitive; Neuropathy; Oral; Pharmaceutical Preparations; Physiological; Pilot Projects; Placebo Control; Placebos; Premature Labor; Prevention; Prevention strategy; Randomized; Research; Research Personnel; Research Proposals; Rest; Risk; Series; Sleep; Study Subject; Terbutaline; Tocolytic Agents; Weight; Work; base; cognitive function; counterregulation; diabetes control; diabetic; dosage; glycemic control; hypoglycemia unawareness; improved; prevent; protocol development; response; type I diabetic; waiver; young adult

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.

描述（由申请人提供）：第 1 节总结了研究者和机构 (WUMS) 的资格，以在智力上和操作上积极参与方案制定、实施、数据分析和结果传播，这些研究与该网络为预防接受胰岛素治疗的糖尿病受试者发生低血糖而进行的研究有关。第 2 部分将概述供网络考虑的具体提案。本文提出的具体建议题为“睡前p2-肾上腺素激动剂治疗预防1型糖尿病儿童低血糖”。我们的建议基于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、低血糖不自觉、运动相关的 HAAF、睡眠相关的 HAAF）以及它们与低血糖风险的关联相关的研究，包括来自我们自己的小组和其他研究人员的研究，并且我们的初步研究表明 p2-肾上腺素能激动剂， 特布他林可减少胰岛素治疗的 1 型糖尿病受试者的夜间低血糖。在此，我们建议进行初步试点研究，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、安慰剂对照临床试验，以确定睡前特布他林是否可以将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。在实现和维持减少糖尿病长期微血管、大血管和神经性并发症所需的水平上建立最佳血糖控制受到低血糖风险的限制。预防低血糖的策略可以实现更好的整体血糖控制，这将代表胰岛素需求型糖尿病管理的重要进步。该研究网络将制定和评估预防低血糖和改善糖尿病控制的策略。