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

尽管1型糖尿病(T1D)的管理有所改善，包括胰岛素类似物，胰岛素泵 治疗，以及最近的持续血糖监测，低血糖的风险仍然是 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 血糖控制仍然是夜间低血糖和餐后血糖不稳定。荷尔蒙减少 夜间和反复低血糖发作后对低血糖的逆调节反应 将试图实现严格控制的T1D患者置于严重低血糖的高危状态，原因是 没有意识到低血糖。非生理性胰岛素给药经常导致餐后早期 高血糖和餐后晚期高胰岛素血症，不仅影响血糖控制，还影响 也会导致不可预测的日间低血糖。这很可能是没有手动的“开环” 治疗性胰岛素方案将能够最佳地控制T1D患者的血糖，并且生物胰岛- 电池更换目前是不可行的。“闭环式”自动化人工胰腺系统，包括 胰岛素泵可以精确地输送可变数量的胰岛素，连续的血糖传感器可以准确地 确定血糖水平，以及基于实时确定胰岛素递送率的有效算法 血糖读数，仍然是控制血糖和减少低血糖的最有希望的干预措施 曝光。本研究的目标是：(1)确定夜间闭环式治疗是否可以 降低或消除夜间低血糖，恢复对 复发性夜间低血糖受试者的低血糖；以及(2)研究是否使用 胰岛素，如普拉林肽和埃塞那肽，当与闭合循环治疗联合使用时，可以 优化餐后血糖控制，消除或降低餐后早期和晚期高血糖 餐后低血糖。这些研究将使用美敦力ePID系统进行，该系统在 几项研究表明，它有望成为第一代闭环系统。我们中心有一个 在临床T1D研究方面表现出色，在以下方面的研究中处于公认的领先地位 低血糖和闭环系统治疗。建议的研究是新颖的、重要的，而且可能会取得进展。 我们不仅了解T1D和低血糖，而且还了解总体上的闭环血糖控制。

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.