Ambulatory Artificial Pancreas: merging physiology, behavior, and control design

动态人工胰腺：融合生理学、行为和控制设计

• 批准号: 8796554
• 负责人: ANANDA BASU
• 金额: $ 10.12万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8796554
• 关键词: Acute; Address; Age; Algorithms; Artificial Pancreas; Automobile Driving; Behavior; Behavior Control; Behavior assessment; Behavioral; Bolus Infusion; California; Carbohydrates; Characteristics; Child; Circadian Rhythms; Clinic; Clinical Research; Complex; Computer Simulation; Computers; Development; Devices; Diabetes Mellitus; Engineering; Environment; Environmental Risk Factor; Event; Exercise; Focus Groups; Frequencies; Fright; Glucagon; Glucose; Glycosylated hemoglobin A; Goals; Group Interviews; Health; Health Personnel; Hepatic; Hour; Human; Hyperglycemia; Hypoglycemia; Individual; Injection of therapeutic agent; Inpatients; Institution; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; International; Learning; Life Style; Measures; Metabolic; Methodology; Methods; Modeling; Monitor; Outpatients; Patients; Pattern; Performance; Persons; Phase; Physiological; Physiology; Preparation; Prevention; Procedures; Psychometrics; Recurrence; Regulation; Research; Research Institute; Risk; Safety; Schedule; Social support; Sports; Structure; Summary Reports; System; Testing; Time; Tracer; Translating; Translations; Validation; Virginia; Work; base; clinical practice; design; engineering design; glycemic control; improved; infancy; innovation; instrument; insulin sensitivity; mathematical model; pancreas development; patient safety; predictive modeling; public health relevance; research study; response; sensor; study characteristics; technology development; tool; trend

DESCRIPTION (provided by applicant): Contemporary studies focus increasingly on the development of artificial pancreas (AP) - an engineering system known as closed-loop control (CLC). The final goal - an ambulatory AP - has the potential to make a tremendous impact on the health and lives of people with type 1 diabetes. Our interdisciplinary international team has been at the forefront of CLC development, creating models, in silico testing platform, safety and control algorithms that represent the state of the art in AP development today. With this project, we bring the quest for ambulatory CLC to a new level, proposing to merge for the first time three key aspects of the optimal control in type 1 diabetes: human behavior, physiology and engineering Our primary goal is to build, test, and validate a new ambulatory CLC system that is informed by, and is adaptive to, real-time changes in behavior and physiology. Our underlying hypothesis is: the rate of behavioral events and the ensuing metabolic responses can be divided into hierarchical time scales, which can be translated into a modular engineering hierarchy with clearly identifiable and tractable control goals at each time scale. Phase 1 - Building assessment algorithms and control modules (primary time scale minutes-hours): We will first characterize the relationships of psycho-behavioral markers and acute behavioral events (e.g. meals, exercise) with the magnitude of physiological response and the need for real-time adaptation of CLC. Engineering tools will be designed responsible for the patient safety and prevention of hypoglycemia and for the 'health' of the AP system on both local and remote levels. We will develop a framework to address system transitions instigated by behavioral challenges and will conduct innovative physiological experiments to assess "dawn" phenomenon, glucose fluxes following complex carbohydrate meal, and hepatic glucagon sensitivity. Phase 2 - Judging the effect size of control components (primary time scale days-weeks): We will engineer an adaptive learning algorithm that recognizes patients' bio-behavioral patterns, such as meal and exercise timing, and diurnal variation in insulin sensitivity. Coordinated clinical studies and large-scale in silico experiments will estimate the effect size of inclusion into CLC of initialization and real-time adaptation control components. Specifically, we will assess the effect of using physiological and behavioral: (i) markers to initialize CLC and (ii) profiles to adjust insulin boluses and basal rate. Phase 3 - System validation and trial of long-term ambulatory CLC: A final multi-center trial will validate our system in patients' natural environment in preparation for its ultimate translation into clinical practice. The primary hypothesis driving Phase 3 is: compared to state-of-the-art sensor augmented open loop therapy, closed-loop control will reduce the frequency of hypoglycemia and will increase the time spent within the target range of 70-180 mg/dl, without compromising average glycemic control as measured by HbA1c. PUBLIC HEALTH RELEVANCE: The artificial pancreas based on closed-loop control, has the potential to make a tremendous impact on the health and lives of people with type 1 diabetes. The development of this technology has made significant strides over the last five years; however, it is still in infancy, currently being tested in inpatient clinical-research center setting. As the transition is made from the clinic to outpatient trials and then to approved ambulatory devices, additional strategies will need to be developed to optimize control and individualize treatment, requiring creative, medically-inspired engineering design and safety monitoring.

描述（由申请人提供）：当代研究越来越关注人工胰腺（AP）的开发--一种被称为闭环控制（CLC）的工程系统。最终的目标-一个流动的AP -有可能对1型糖尿病患者的健康和生活产生巨大的影响。我们的跨学科国际团队一直处于CLC开发的最前沿，创建代表当今AP开发最先进水平的模型，计算机测试平台，安全和控制算法。通过这个项目，我们将对流动CLC的追求提升到一个新的水平，首次提出合并1型糖尿病最佳控制的三个关键方面：人类行为，生理学和工程学我们的主要目标是建立，测试和验证一个新的流动CLC系统，该系统由行为和生理学的实时变化提供信息，并能适应这些变化。我们的基本假设是：行为事件的速率和随后的代谢反应可以被划分为分级时间尺度，其可以被转换为模块化工程分级，在每个时间尺度具有清晰可识别和易处理的控制目标。第1阶段-建立评估算法和控制模块（主要时间尺度分钟-小时）：我们将首先描述心理行为标志物和急性行为事件（例如进餐，运动）与生理反应幅度的关系以及CLC实时适应的需要。工程工具的设计将负责患者安全和低血糖预防，以及本地和远程AP系统的“健康”。我们将开发一个框架来解决由行为挑战引发的系统转换，并将进行创新的生理实验来评估“黎明”现象，复合碳水化合物餐后的葡萄糖通量和肝胰高血糖素敏感性。第2阶段-判断对照成分的效应大小（主要时间尺度天-周）：我们将设计一种自适应学习算法，该算法可以识别患者的生物行为模式，例如进餐和运动时间以及胰岛素敏感性的昼夜变化。协调的临床研究和大规模计算机模拟实验将估计初始化和实时自适应控制组件纳入CLC的效应量。具体而言，我们将评估使用生理和行为的影响：（i）标记物初始化CLC和（ii）配置文件调整胰岛素推注和基础率。第3阶段-长期门诊CLC的系统验证和试验：最终的多中心试验将在患者的自然环境中验证我们的系统，为其最终转化为临床实践做准备。驱动第3阶段的主要假设是：与最先进的传感器增强开环治疗相比，闭环控制将降低低血糖的频率，并将增加在70-180 mg/dl的目标范围内花费的时间，而不影响通过HbA 1c测量的平均血糖控制。 公共卫生相关性：基于闭环控制的人工胰腺有可能对1型糖尿病患者的健康和生活产生巨大影响。这项技术的发展在过去五年中取得了重大进展;然而，它仍处于起步阶段，目前正在住院临床研究中心进行测试。随着从诊所到门诊试验，再到获批的门诊设备的过渡，需要开发额外的策略来优化控制和个性化治疗，这需要创造性的、受医学启发的工程设计和安全监测。

项目成果

Design and in silico evaluation of an intraperitoneal-subcutaneous (IP-SC) artificial pancreas.

• DOI: 10.1016/j.compchemeng.2014.02.024
• 发表时间: 2014-11-05
• 期刊: Computers & chemical engineering
• 影响因子: 4.3
• 作者: Lee JJ;Dassau E;Zisser H;Doyle FJ 3rd
• 通讯作者: Doyle FJ 3rd

Clinical results of an automated artificial pancreas using technosphere inhaled insulin to mimic first-phase insulin secretion.

使用技术圈吸入胰岛素模拟第一阶段胰岛素分泌的自动化人工胰腺的临床结果。

• DOI: 10.1177/1932296815582061
• 发表时间: 2015
• 期刊: Journal of diabetes science and technology
• 影响因子: 5
• 作者: Zisser,Howard;Dassau,Eyal;Lee,JustinJ;Harvey,RebeccaA;Bevier,Wendy;Doyle3rd,FrancisJ
• 通讯作者: Doyle3rd,FrancisJ

Artificial pancreas goes outpatient: a new diabetes ecosystem.

人工胰腺进入门诊：一个新的糖尿病生态系统。

• DOI: 10.1177/193229681300700601
• 发表时间: 2013
• 期刊: Journal of diabetes science and technology
• 影响因子: 5
• 作者: Renard,Eric;Cobelli,Claudio;Zisser,HowardC;Kovatchev,BorisP
• 通讯作者: Kovatchev,BorisP

Lifestyle modifications in the management of type 1 diabetes: still relevant after all these years?

生活方式改变在 1 型糖尿病治疗中的作用：这么多年过去了，仍然有意义吗？

• DOI: 10.1089/dia.2014.0175
• 发表时间: 2014
• 期刊: Diabetes technology & therapeutics
• 影响因子: 5.4
• 作者: Gonder-Frederick,Linda

Empirical Dynamic Model Identification for Blood-Glucose Dynamics in Response to Physical Activity.

• DOI: 10.1109/cdc.2015.7402815
• 发表时间: 2015-12
• 期刊: Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control
• 作者: Dasanayake IS;Seborg DE;Pinsker JE;Doyle FJ 3rd;Dassau E
• 通讯作者: Dassau E