Closed-loop Artificial Pancreas: Algorithm Engineering and Clinical Evaluation

闭环人工胰腺： 算法工程和临床评价 摘要 这项建议旨在建立在一个有希望的研究路线，已经产生了一个工作原型 闭环人工胰腺（AP）结合了连续葡萄糖传感和自动胰岛素 通过控制算法进行递送。AP由三个组件组成：连续葡萄糖传感器、 持续皮下胰岛素输注泵和人工胰腺软件（APS）。APS进入了决赛 美国食品药品监督管理局对全自动闭环控制临床应用的审查阶段 试验（主文件MAF-1625）。 具体目标是：1）开发人工胰腺，以优化胰岛素输送， 2）人工胰腺的扩展，以包括改变和个体 胰岛素敏感性的差异，以及3）使用多参数模型进一步开发算法 预测控制（mpMPC），以减少在线计算，发展有效的在线监测 确保AP正常运行并适应多输入系统的策略。高尔夫领域 为了实现我们的胰岛素输送完全自动化闭环装置的总体目标，我们将利用 分阶段方法，其中临床研究也有并行工程设计方法，以便 完善我们的AP。计算机模拟测试和人体临床测试将用于验证模型的每个步骤 发展 这一系列研究的最终目标是一个功能性AP，将提供全天候葡萄糖 通过控制胰岛素输送来调节，以响应检测到的葡萄糖水平的变化模式， 以在患有1型糖尿病的受试者中实现最佳葡萄糖调节。将给予特别考虑 在设置约束条件时， 后续胰岛素输注。该提案描述了多参数模型预测控制方法， 血糖调节以及AP在过夜、用餐和运动条件下的广泛计算机模拟和临床验证 条件 该应用程序源于美国大学系统工程师之间的长期合作。 加州，圣巴巴拉（UCSB）和研究医生专门从事糖尿病研究，在著名的 Sansum糖尿病研究所（Sansum）距离酒店不到10英里。这支队伍已经 作为人工胰腺文献的主要贡献者和糖尿病领域的国际领导者， 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.