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

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 1 型糖尿病 (T1D) 的治疗有所改善，包括胰岛素类似物、胰岛素泵 治疗，以及最近的连续血糖监测，低血糖的风险仍然是一个 实现接近正常血糖控制的主要障碍。接近正常的两个常见障碍 血糖控制仍存在夜间低血糖和餐后血糖不稳定的情况。荷尔蒙减少 夜间和低血糖反复发作后对低血糖的反调节反应 由于以下原因，试图严格控制的 T1D 患者面临严重低血糖的高风险 低血糖无意识。非生理性胰岛素输送经常导致餐后早期 高血糖和餐后晚期高胰岛素血症，不仅影响血糖控制，而且 也会导致不可预测的白天低血糖。很可能没有手动，“开环” 治疗性胰岛素方案将能够最佳地控制 1 型糖尿病患者的血糖，并且生物胰岛 细胞更换目前是不可行的。 “闭环”自动化人工胰腺系统，包括 胰岛素泵可精确输送可定量的胰岛素，连续葡萄糖传感器可准确地输送胰岛素 确定血糖水平，以及基于实时确定胰岛素输送速率的有效算法 血糖读数仍然是控制血糖和减少低血糖最有希望的干预措施 接触。本研究的目的是（1）确定夜间闭环疗法是否可以 减少或消除夜间低血糖并恢复反调节激素的反应性 反复发生夜间低血糖的受试者的低血糖； (2) 调查是否使用 肠降血糖素，如普兰林肽和艾塞那肽，与闭环疗法联合使用时，可以 优化餐时血糖控制，消除或减少早期餐后高血糖和晚期餐后高血糖 餐后低血糖。这些研究将使用美敦力 (Medtronic) ePID 系统进行，该系统在 多项研究显示出作为第一代闭环设备的前景。我们中心有一个 在 T1D 临床研究方面表现出色，并且是相关研究领域公认的领导者 低血糖和闭环治疗。拟议的研究新颖、重要且可能取得进展 我们不仅了解 T1D 和低血糖，还了解一般的闭环血糖控制。