Closed-loop Artificial Pancreas: Algorithm Engineering and Clinical Evaluation

闭合式人工胰腺： 算法工程与临床评估 摘要 这项提议寻求建立在一系列有希望的研究的基础上，这些研究已经产生了一个工作原型 将连续血糖感应和自动胰岛素相结合的闭环式人工胰腺(AP) 通过控制算法交付。AP由三个组件组成：一个连续的血糖传感器，一个 连续皮下胰岛素输注泵和人工胰腺软件(APS)。APS进入决赛 美国食品和药物管理局用于全自动闭环临床控制的审查阶段 试验(主文件MAF-1625)。 其具体目标是：1)开发人工胰腺，以优化胰岛素的输送，并将 与饮食相关的血糖漂移，2)人工胰腺的扩张，包括改变和个体 胰岛素敏感性的差异，以及3)多参数模型算法的进一步发展 预测控制(MpMPC)为了减少在线计算量，开发有效的在线监测 确保AP正常运行并容纳多个输入系统的策略。在探索过程中 为了实现我们的总体目标，即胰岛素输送的全自动闭环装置，我们将利用一种 临床研究也有并行工程设计方法的阶段性方法，以便 完善我们的美联社。在硅胶测试和人体临床测试中，将用于验证模型的每一步 发展。 这一系列研究的最终目标是一种能够全天候提供葡萄糖的功能性AP 根据检测到的血糖水平变化模式，通过受控胰岛素释放进行调节 以便在1型糖尿病患者中实现最佳的血糖调节。我们会特别考虑 在设置限制条件时，根据先前输注的潜在可用胰岛素量(板载胰岛素) 随后的胰岛素注射。该方案描述了多参数模型预测控制方法 过夜、进餐和锻炼下AP的血糖调节和广泛的硅胶和临床验证 条件。 这个应用程序源于芝加哥大学系统工程师之间的长期合作 加州圣巴巴拉(UCSB)和著名的糖尿病研究中心的研究医生 桑苏姆糖尿病研究所(桑苏姆)距离酒店不到10英里。这支队伍已经出类拔萃 作为人工胰腺文献的主要贡献者和糖尿病的国际领先者 技术

Closed-loop Artificial Pancreas: Algorithm Engineering and Clinical Evaluation ABSTRACT This proposal seeks to build on a promising line of research that has already resulted in a working prototype of a closed-loop artificial pancreas (AP) that combines continuous glucose sensing with automated insulin delivery via a control algorithm. The AP consists of three components: a continuous glucose sensor, a continuous subcutaneous insulin infusion pump, and artificial pancreas software (APS). The APS is in the final stages of review by the Food and Drug Administration for use in fully automated closed-loop control clinical trials (Master File MAF-1625 ). The specific aims are: 1) Development of the Artificial Pancreas to optimize insulin delivery and minimize meal-related excursions in glucose, 2) Expansion of the Artificial Pancreas to include alterations and individual differences in insulin sensitivity, and 3) Further development of the algorithms using multi-parametric model predictive control (mpMPC) in order to reduce online computation, develop effective online monitoring strategies to ensure that the AP is operating properly, and accommodate multiple input systems. In the quest to achieve our overall goal of a completely automated closed-loop device for insulin delivery, we will utilize a staged approach in which the clinical studies also have a concurrent engineering design approach in order to refine our AP. In silico testing and human in-clinic testing will be used to validate each step of model development. The ultimate goal of this line of research is a functional AP that will provide around-the-clock glucose regulation through controlled insulin delivery in response to detected patterns of changes in glucose levels in order to achieve optimal glucose regulation in subjects with type 1 diabetes. Special consideration will be given to the amount of potentially available insulin from prior infusions (insulin-on-board) in setting constraints for subsequent insulin delivery. The proposal describes multi-parametric model predictive control approaches to glycemic regulation and extensive in silico and clinical validation of the AP under overnight, meal, and exercise conditions. This application grows out of a long-standing collaboration between systems engineers at the University of California, Santa Barbara (UCSB) and research physicians specializing in diabetes research at the prestigious Sansum Diabetes Research Institute (Sansum) located less than ten miles away. This team has distinguished itself as a major contributor to the artificial pancreas literature and as an international leader in diabetes technology.