The Optimal Pathway to Implanted Autonomous Insulin Delivery

项目摘要/摘要 热衣汗·拉尔医学博士是斯坦福大学成人和儿科内分泌科的讲师。 作为一名患有1型糖尿病的电气工程师和计算机科学家，他的主要研究兴趣是 设计、开发和测试新的糖尿病技术。这份K23提案将提供一个结构化的 在正式导师的指导下进行临床研究培训的经验，将使Lal博士成为一名独立的 具有胰岛素自动给药专业知识的临床研究人员。 皮下“混合”闭环系统基于连续的血糖数据调节胰岛素递送，但 要求用户宣布用餐。尽管随机对照试验前景看好，但我们发表的现实世界试验 第一个商业皮下系统的经验表明，46%的用户完全呈现在临床上 在1年内停止使用“自动模式”。虽然可能会克服一些障碍，但最佳技术 解决方案需要高用户满意度和最优的血糖控制，并将用户干预降至最低。 在这一应用中，拉尔博士提出了几项研究，以了解和优化腹膜腔内给药 未来自主植入系统的胰岛素。腹膜腔内注射胰岛素的作用速度比 皮下注射。胰岛素作用的“尾巴”也更短，更容易上调和下调。 胰岛素水平和更少的时间延迟，这对于自动胰岛素传递是必不可少的。腹膜腔胰岛素 分娩也能部分恢复胰升糖素对低血糖和运动的反应，即使是长期存在的1型糖尿病患者也是如此 糖尿病。改进的动力学和恢复的胰高血糖素分泌的安全性使该系统成为完全 自动注射胰岛素。在植入物的使用者中也有显著的积极体验 腹膜腔胰岛素治疗。 拉尔博士研究的具体目的是：(1)评估BMI、身体成分、骨骼健康和人类因素 与以蒙彼利埃为中心的全球用户的腹膜腔内胰岛素有关，并将其与 与使用皮下胰岛素的1型糖尿病患者配对，(2)评估速度和胰高血糖素计数器 对腹膜腔内快速作用胰岛素的调节反应(FIAsp)，以及(3)使用可用数据 在计算机模拟中执行并确定将血糖控制保持在(70-180 mg/dL)范围内的控制策略 在各种模拟条件下。他的导师包括白金汉、马斯、胡德和雷纳德博士。 糖尿病技术的全球领先者。 除了流行病学、统计学、研究设计、人类保护和伦理学方面的课程外，拉尔·威尔博士 我还寻求生物设计学院的奖学金，在斯坦福大学提供，以促进新健康的发展 技术拉尔博士的长期研究目标是与一家糖尿病设备制造商合作， 生理学设备(见彼得·洛德的支持信)，以开发和测试植入的完全闭合环 腹膜腔内胰岛素给药系统，优化范围内的时间，消除糖尿病的日常负担。

PROJECT SUMMARY/ABSTRACT Rayhan A. Lal, MD is an Instructor in the Divisions of Adult and Pediatric Endocrinology at Stanford University. As an electrical engineer and computer scientist with type 1 diabetes, his primary research interest is the design, development and testing of new diabetes technologies. This K23 proposal will provide a structured clinical research training experience with formal mentorship that will enable Dr. Lal to become an independent clinical researcher with expertise in automated insulin delivery. Subcutaneous “hybrid” closed-loop systems modulate insulin delivery based on continuous glucose data but require users to announce meals. Despite promising randomized controlled trials, our published real-world experience with the first commercial subcutaneous system shows that 46% of users presenting to clinic entirely discontinue “Auto Mode” within 1 year. While some barriers may be overcome, the optimal technological solution requires high user satisfaction and optimal glycemic control with minimal user intervention. In this application, Dr. Lal proposes several studies to understand and optimize the intraperitoneal delivery of insulin for a future autonomous implantable system. Intraperitoneal insulin delivery acts faster than subcutaneous. The “tail” of insulin action is also shorter, making it easier to upregulate and downregulate insulin levels with fewer time delays which is essential for automated insulin delivery. Intraperitoneal insulin delivery also partially restores glucagon response to hypoglycemia and exercise, even in long-standing type 1 diabetes. The improved kinetics and safety from restored glucagon secretion make this system ideal for fully automated insulin delivery. There is also a significant positive experience among users of implanted intraperitoneal insulin therapy. The specific aims of Dr. Lal’s study are to: (1) evaluate BMI, body composition, bone health and human factors associated with intraperitoneal insulin among worldwide users, centered in Montpellier, and compare them to matched controls with type 1 diabetes using subcutaneous insulin, (2) assess the speed and glucagon counter- regulatory response to intraperitoneal faster acting insulin apart (Fiasp), and (3) use the available data to perform in silico modeling and determine a control strategy that keeps glycemic control in range (70-180mg/dL) over a variety of simulated conditions. His mentors include Drs. Buckingham, Maahs, Hood and Renard worldwide leaders in diabetes technology. In addition to coursework in epidemiology, statistics, study design, human protection and ethics, Dr. Lal will also pursue a Biodesign faculty fellowship, offered at Stanford to promote the development of new health technology. Dr. Lal’s long-term research objective is to collaborate with a diabetes device manufacturer, PhysioLogic Devices (see letter of support from Peter Lord), to develop and test an implanted fully closed-loop intraperitoneal insulin delivery system, optimizing time in range and eliminating the daily burdens of diabetes.