The Optimal Pathway to Implanted Autonomous Insulin Delivery

植入式自主胰岛素输送的最佳途径

• 批准号: 10611387
• 负责人: Rayhan Lal
• 金额: $ 19.05万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611387
• 关键词: Acute; Adult; Algorithms; American; Blood Vessels; Body Composition; Body fat; Body mass index; Cardiovascular Diseases; Caring; Catheters; Cause of Death; Childhood; Clinic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complications of Diabetes Mellitus; Computers; Continuous Glucose Monitor; Coronary Arteriosclerosis; Data; Death Certificates; Development; Devices; Diabetes Mellitus; Drug Kinetics; Electrical Engineering; Endocrinology; Epidemiology; Ethics; Exercise; FDA approved; Faculty; Fellowship; Formulation; Future; Glucagon; Glucose; Glycosylated hemoglobin A; Goals; Health Technology; Healthcare; Human; Hybrids; Hyperglycemia; Hypoglycemia; Implant; Individual; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intervention; Intravenous; Investigation; Investments; Kidney Diseases; Kinetics; Letters; Location; Manufacturer; Mentors; Mentorship; Modeling; Morbidity - disease rate; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathway interactions; Patients; Peritoneal; Peritoneum; Persons; Physiological; Population; Positioning Attribute; Prevention; Publishing; Pump; Randomized, Controlled Trials; Recommendation; Reporting; Research; Research Design; Research Personnel; Research Training; Retinal Diseases; Route; Running; Safety; Scientist; Speed; Structure; System; Tail; Technology; Testing; Therapeutic; Time; Trust; United States; Universities; Visceral; Work; age group; blood glucose regulation; bone health; cardiovascular risk factor; cohort; design; diabetes risk; experience; glycemic control; improved; in silico; innovation; instructor; interest; intraperitoneal; novel; performance tests; response; satisfaction; socioeconomics; statistics; subcutaneous

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.

项目总结/摘要 Rayhan A.拉尔博士是斯坦福大学成人和儿童内分泌学系的讲师。 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、开发和测试糖尿病新技术。K23提案将提供结构化的 临床研究培训经验与正式的指导，将使拉尔博士成为一个独立的 具有自动胰岛素输注专业知识的临床研究员。 皮下“混合”闭环系统基于连续葡萄糖数据调节胰岛素输送， 要求用户公布用餐时间。尽管有希望的随机对照试验，我们发表的真实世界 第一个商业皮下系统的经验表明，46%的用户完全进入诊所 1年内停止使用“自动模式”。虽然可以克服一些障碍，但最佳的技术 解决方案需要高用户满意度和最佳血糖控制，同时用户干预最少。 在本申请中，Lal博士提出了几项研究，以了解和优化腹膜内递送 用于未来自主植入系统的胰岛素。腹膜内胰岛素输注比 皮下注射胰岛素作用的“尾巴”也更短，更容易上调和下调 这对于自动胰岛素输送是必不可少的。腹腔注射胰岛素 即使在长期存在的1型糖尿病患者中， 糖尿病来自恢复的胰高血糖素分泌的改善的动力学和安全性使该系统成为充分应用的理想选择。 自动输注胰岛素。在植入的使用者中也有显著的积极体验。 腹膜内胰岛素治疗。 拉尔博士研究的具体目的是：（1）评估BMI、身体成分、骨骼健康和人为因素 与以蒙彼利埃为中心的全球使用者中的腹膜内胰岛素相关，并将其与 使用皮下胰岛素的1型糖尿病匹配对照，（2）评估速度和胰高血糖素计数器- 对腹膜内速效胰岛素（Fiasp）的调节反应，以及（3）使用可用数据， 进行计算机模拟建模，并确定将血糖控制在范围（70- 180 mg/dL）内的控制策略 在各种模拟条件下。他的导师包括白金汉博士，Maahs，Hood和Renard 糖尿病技术的全球领导者。 除了流行病学，统计学，研究设计，人类保护和伦理学课程外，Lal博士还将 我还追求生物设计教师奖学金，在斯坦福大学提供，以促进新的健康发展 技术.拉尔博士的长期研究目标是与糖尿病设备制造商合作， PhysioLogic器械（参见Peter Lord的支持信），用于开发和测试植入式全闭环 腹膜内胰岛素输送系统，优化范围内的时间，消除糖尿病的日常负担。

项目成果

Insulin Delivery Hardware: Pumps and Pens.

胰岛素输送硬件：泵和笔。

• DOI: 10.1089/dia.2021.2503
• 发表时间: 2021
• 期刊: Diabetes technology & therapeutics
• 影响因子: 5.4
• 作者: Lal,RayhanA;Leelarathna,Lalantha
• 通讯作者: Leelarathna,Lalantha

Discontinued Use of the Loop Insulin Dosing System: A Mixed-Methods Investigation.

循环胰岛素给药系统的停止使用：混合方法调查。

• DOI: 10.1089/dia.2021.0362
• 发表时间: 2022
• 期刊: Diabetes technology & therapeutics
• 影响因子: 5.4
• 作者: Wong,JessieJ;Suttiratana,SakinahC;Lal,RayhanA;Lum,JohnW;Lanning,MonicaS;Dunlap,Adrienne;Arbiter,Brandon;Hanes,SarahJ;Bailey,RyanJ;Hood,KoreyK;Naranjo,Diana
• 通讯作者: Naranjo,Diana

The Promising Success of Project Extension for Community Healthcare Outcomes (ECHO) Diabetes: Case Series.

• DOI: 10.2196/46050
• 发表时间: 2023-08-03
• 期刊: JMIR diabetes

Project ECHO Diabetes Cost Modeling to Support the Replication and Expansion of Tele-mentoring Programs in Non-research Settings.

• DOI: 10.1007/s13300-022-01364-3
• 发表时间: 2023-03
• 期刊: Diabetes therapy : research, treatment and education of diabetes and related disorders
• 作者: Lewit EM;Figg LE;Addala A;Filipp SL;Lal R;Gurka MJ;Herndon JB;Haller MJ;Maahs DM;Walker AF;Project ECHO Diabetes Research Team
• 通讯作者: Project ECHO Diabetes Research Team

Tele-education model for primary care providers to advance diabetes equity: Findings from Project ECHO Diabetes.

• DOI: 10.3389/fendo.2022.1066521
• 发表时间: 2022
• 期刊: FRONTIERS IN ENDOCRINOLOGY
• 影响因子: 5.2
• 作者: Addala, Ananta;Filipp, Stephanie L.;Figg, Lauren E.;Anez-Zabala, Claudia;Lal, Rayhan A.;Gurka, Matthew J.;Haller, Michael J.;Maahs, David M.;Walker, Ashby F.
• 通讯作者: Walker, Ashby F.