Yale Study of Closed-Loop Automated Glucose Control for Hypoglycemia Prevention

耶鲁大学闭环自动血糖控制预防低血糖的研究

• 批准号: 7932071
• 负责人: STUART ALAN WEINZIMER
• 金额: $ 36.74万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932071
• 关键词: Achievement; Adolescent; Affect; Algorithms; Artificial Pancreas; Biological; Blood Glucose Self-Monitoring; Child; Childhood; Clinical; Clinical Research; Devices; Exercise; External Infusion Pumps; Generations; Glucose; Glycosylated hemoglobin A; Grant; Health Personnel; Home environment; Hormonal; Hormones; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Infusion procedures; Injection of therapeutic agent; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intervention; Islet Cell; Manuals; Outcome; Patients; Physiological; Pilot Projects; Pramlintide; Prevention; Progress Reports; Protocols documentation; Randomized; Randomized Controlled Trials; Reading; Recurrence; Regimen; Research; Research Design; Risk; Study Section; System; Therapeutic; Time; analog; base; blood glucose regulation; clinical practice; exenatide; glucose monitor; glucose sensor; glycemic control; high risk; hypoglycemia unawareness; novel; prevent; response; subcutaneous; systems research; young adult; Achievement; Adolescent; Affect; Algorithms; Artificial Pancreas; Biological; Blood Glucose Self-Monitoring; Child; Childhood; Clinical; Clinical Research; Devices; Exercise; External Infusion Pumps; Generations; Glucose; Glycosylated hemoglobin A; Grant; Health Personnel; Home environment; Hormonal; Hormones; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Infusion procedures; Injection of therapeutic agent; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intervention; Islet Cell; Manuals; Outcome; Patients; Physiological; Pilot Projects; Pramlintide; Prevention; Progress Reports; Protocols documentation; Randomized; Randomized Controlled Trials; Reading; Recurrence; Regimen; Research; Research Design; Risk; Study Section; System; Therapeutic; Time; analog; base; blood glucose regulation; clinical practice; exenatide; glucose monitor; glucose sensor; glycemic control; high risk; hypoglycemia unawareness; novel; prevent; response; subcutaneous; systems research; young adult

Despite improvements in the management of type 1 diabetes (T1D), including insulin analogs, insulin pump therapy, and most recently, continuous glucose monitoring, the risk of hypoglycemia continues to serve as a major barrier to the achievement of near-normal glucose control. Two common obstacles to near-normal glucose control remain night-time hypoglycemia and post-prandial glycemic instability. Decreased hormonal counter-regulatory responsiveness to hypoglycemia at night and after repeated episodes of hypoglycemia places patients with T1D attempting to achieve tight control at high risk of severe hypoglycemia due to hypoglycemia unawareness. Non-physiological insulin delivery frequently results in early post-prandial hyperglycemia and late post-prandial hyperinsulinemia, affecting not only glycemic control but also contributing as well to unpredictable daytime hypoglycemia. It is likely that no manual, "open-loop" therapeutic insulin regimen will be able to optimally control glycemia in patients with T1D, and biological islet- cell replacement is presently unfeasible. "Closed-loop" automated artificial pancreas systems, consisting of an insulin pump to precisely deliver variable amounts of insulin, a continuous glucose sensor to accurately determine the glucose levels, and effective algorithms to determine insulin delivery rates based on real-time glucose readings, remains the most promising intervention to control glycemia and reduce hypoglycemia exposure. The objectives of this study are (1) to determine whether night-time closed-loop therapy can reduce or eliminate nocturnal hypoglycemia and restore counter-regulatory hormone responsiveness to hypoglycemia in subjects with recurrent nocturnal hypoglycemia; and (2) to investigate whether the use of incretins such as pramlintide and exenatide, when used in conjunction with closed-loop therapy, can optimize prandial glycemic control, eliminating or reducing both early post-prandial hyperglycemia and late post-prandial hypoglycemia. These studies will be performed with the Medtronic ePID system, which in several studies, has shown promise as a first-generation closed-loop device. Our center has a demonstrated track record in clinical T1D research and a well-recognized leader in studies involving hypoglycemia and closed-loop therapy. The proposed studies are novel, important, and likely to advance our understanding not only of T1D and hypoglycemia, but also closed-loop glucose control in general.

尽管改善了1型糖尿病（T1D）的管理，包括胰岛素类似物，胰岛素泵 疗法以及最近的连续葡萄糖监测，低血糖的风险继续充当 实现近正常葡萄糖控制的主要障碍。近正常的两个常见障碍 葡萄糖控制仍然是夜间低血糖症和餐后血糖不稳定性。荷尔蒙减少 夜间和反复发作性低血糖的反应性反应性低血糖的反应性 将T1D的患者试图以高度严重低血糖症的高风险进行严重控制的患者 低血糖不认识。非生理胰岛素输送经常导致早期餐 高血糖和晚期餐后高胰岛素血症，不仅影响血糖控制，还会影响 也导致了不可预测的白天低血糖症。可能没有手册“开环” 治疗性胰岛素方案将能够最佳地控制T1D患者和生物学胰岛的血糖 细胞更换目前是不可行的。 “闭环”自动人工胰腺系统，由 胰岛素泵以精确地提供可变量的胰岛素，连续的葡萄糖传感器准确 确定葡萄糖水平和有效算法以根据实时确定胰岛素输送率 葡萄糖读数仍然是控制血糖并减少低血糖的最有希望的干预措施 接触。这项研究的目标是（1）确定夜间闭环治疗是否可以 降低或消除夜间低血糖症并恢复反调节激素的反应性 患有复发性夜间低血糖的受试者中低血糖； （2）调查是否使用 与闭环治疗结合使用时，肠降直降凝集素，例如pramlintide和chenatide，可以 优化丙二氏血糖控制，消除或减少早期原发性高血糖和晚期 餐后低血糖。这些研究将使用Medtronic Epid系统进行，该系统在 几项研究表明，有望作为第一代闭环装置。我们的中心有一个 在临床T1D研究中证明了往绩，并且在涉及的研究中得到了公认的领导者 低血糖和闭环治疗。拟议的研究是新颖的，重要的，并且很可能进步 我们不仅了解T1D和低血糖，而且对一般的闭环葡萄糖控制。