Optimization of an Adaptive Dual-Hormone External Endocrine Pancreas.

自适应双激素外内分泌胰腺的优化。

• 批准号: 8327122
• 负责人: Joseph El Youssef
• 金额: $ 17.32万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8327122
• 关键词: Address; Adrenal Cortex Hormones; Adverse effects; Algorithms; Animals; Beta Cell; Biological Models; Bolus Infusion; Buffers; Cell physiology; Clinical; Clinical Research; Communities; Complications of Diabetes Mellitus; Data; Development; Diabetes Mellitus; Dose; Drug Kinetics; Educational process of instructing; Engineering; Ergometry; Exercise; Exhibits; FDA approved; Failure; Family suidae; Glucagon; Glucose; Glycine; Goals; Health; Health Sciences; Hormones; Human; Hyperglycemia; Hypoglycemia; Infusion procedures; Institutes; Instruction; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Investigation; Islets of Langerhans; Liver Glycogen; Mediating; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Modeling; Modification; Octreotide; Oregon; Outpatients; Personal Satisfaction; Persons; Pharmacodynamics; Physicians; Placebos; Plasma; Preparation; Prevention; Principal Investigator; Property; Research; Research Institute; Research Personnel; Risk; Scientist; Services; Software Tools; Solutions; System; Systems Development; Testing; Translational Research; Universities; Update; Workplace; Zinc; analog; base; chemical stability; comparative; computer program; design; experience; glucose monitor; glucose sensor; glucose uptake; glycemic control; human study; improved; insulin sensitivity; models and simulation; novel; prevent; programs; response; skills; theories; ward

DESCRIPTION (provided by applicant): The Principal Investigator, Dr. Joseph El Youssef, under the mentorship of Drs. Kenneth Ward, Andrew Ahmann and Charles Roberts at the Oregon Health and Science University (OHSU), will undertake the project entitled "Optimization of an Adaptive Dual-Hormone External Endocrine Pancreas". Utilizing the services of the Oregon Clinical and Translational Research Institute (OCTRI), and the Department of Comparative Medicine at OHSU, Dr. El Youssef intends to improve the efficiency of an adaptive closed loop system which automatically delivers insulin and glucagon subcutaneously to persons with diabetes in response to glucose levels obtained by subcutaneously inserted continuous glucose monitors. These studies will assist in the progression of his clinical research skills, supplemented by an OHSU course in the Human Investigation Program (HIP) certificate program, designed to educate and develop young investigators in clinical and translational research. Dr. El Youssef will design and carry out animal studies geared towards testing the pharmacokinetic and dynamic properties of novel preparations of insulin and glucagon, in order to improve closed-loop glycemic control. In addition, Dr. El Youssef will develop skills in computer programming and control theory, with classes at Portland State University and at the Rensselaer Polytechnic Institute in Troy, NY, taught by long-term collaborator Dr. Wayne Bequette, who will also provide instruction in control theory and the software tools needed for modeling and simulation. These courses will provide Dr. El Youssef with experience in algorithm development and system modeling, important requirements for independent progression in this field. Mr. John Lum at the Jaeb Center for Health Research has agreed to collaborate with Dr. El Youssef, providing access to the FDA-approved 300 person simulator for testing of algorithm updates, with which Dr. El Youssef is familiar. The clinical aspect of the proposal is to successively refine iterations of the Adaptive Proportional Derivative algorithm in persons with Type 1 diabetes over the five years of the mentored project. The anticipated improvements in the closed loop glycemic control system will include: (a) adapting the system for corticosteroid-induced insulin resistance and for exercise-induced increases in insulin sensitivity; (b) reducing pre-meal open-loop insulin delivery by creating a "meal mode" component designed for use with a faster-onset zinc-free insulin preparation (Linjeta, from Biodel, Inc); (c), developing a total-body glucagon model and incorporating it into the algorithm to optimize the way in which the algorithm calls for glucagon delivery in order to maximize hypoglycemia prevention and to minimize hepatic glycogen depletion. Appropriately-powered studies in subjects with Type 1 diabetes will address each of these questions. As this mentored project comes to a close, Dr. El Youssef will become an independent researcher in diabetology, with a focus on closed-loop insulin/glucagon delivery systems, and developing into a physician-scientist who can provide ongoing contributions in the field of automated glycemic control in persons with Type 1 diabetes.

描述(由申请人提供)：首席研究员Joseph El Youssef博士在俄勒冈健康与科学大学(OHSU)Kenneth Ward、Andrew Ahmann和Charles Roberts博士的指导下，将承担题为“优化适应性双激素体外内分泌胰腺”的项目。利用俄勒冈州临床与翻译研究所(OCTRI)和俄勒冈州卫生与公众服务部比较医学系的服务，El Youssef博士打算提高自适应闭环系统的效率，该系统根据皮下植入的连续血糖监测仪获得的血糖水平，自动将胰岛素和胰升糖素输送到糖尿病患者的皮下。这些研究将有助于他的临床研究技能的进步，并辅之以OHSU人类调查计划(HIP)证书计划的课程，旨在教育和发展临床和翻译研究方面的年轻研究人员。El Youssef博士将设计和进行动物研究，旨在测试新型胰岛素和胰升糖素制剂的药代动力学和动力学特性，以改善闭环血糖控制。此外，El Youssef博士将在波特兰州立大学和纽约州特洛伊市的伦斯勒理工学院由长期合作伙伴韦恩·贝奎特博士授课，培养计算机编程和控制理论方面的技能，后者还将教授控制理论以及建模和仿真所需的软件工具。这些课程将为El Youssef博士提供算法开发和系统建模方面的经验，这是在该领域独立发展的重要要求。Jaeb健康研究中心的John Lum先生已经同意与El Youssef博士合作，允许他使用FDA批准的300人模拟器来测试算法更新，El Youssef博士对此很熟悉。该提案的临床方面是在指导项目的五年时间里，在1型糖尿病患者中连续改进自适应比例导数算法的迭代。闭环血糖控制系统的预期改进将包括：(A)调整系统以适应皮质类固醇诱导的胰岛素抵抗和运动诱导的胰岛素敏感性；(B)通过创建与更快起效的无锌胰岛素制剂(Biodel，Inc.)一起使用的“进餐模式”组件，减少餐前开环胰岛素供应；(C)开发全身高血糖素模型并将其纳入算法，以优化算法要求高血糖素供应的方式，以最大限度地预防低血糖和最大限度地减少肝糖原消耗。对1型糖尿病患者进行的适当的研究将解决这些问题中的每一个。随着这一指导项目的结束，El Youssef博士将成为糖尿病领域的独立研究员，专注于胰岛素/胰高血糖素的闭环给药系统，并发展成为一名内科科学家，能够在1型糖尿病患者的自动血糖控制领域做出持续贡献。