Introduction of Heart Rate Monitoring to the Closed-Loop Control of T1DM

描述(申请人提供)：拟议的研究重点是1型糖尿病(T1 DM)患者在运动过程中和运动后血糖/胰岛素动力学的变化，并通过代谢模型对其进行量化。一旦确定并量化，这些动态可用于调整胰岛素的释放以响应体力活动，从而避免低估或高估胰岛素需求。锻炼既可以宣布，也可以通过心率监测来检测。增加心率监测将允许将运动过度或补偿不足后经常出现的低血糖和高血糖发作降至最低。这样的优化将适用于标准的胰岛素治疗(基础和膳食推注)、开环血糖控制(适应性基础和推注模式)，并将在任何闭环应用中至关重要。糖尿病技术的最新进展包括两个快速发展的平行领域：胰岛素输送装置(皮下或植入的胰岛素泵)和连续血糖监测仪(CGM)，用于记录频繁的血糖测定。初步研究表明，这两种类型的设备可以在一个闭环的血糖控制系统中成功地连接在一起，但这些系统将如何对不是由膳食触发的代谢紊乱做出反应，如锻炼。体力活动已被广泛认为是治疗T1 DM患者的基本要素。然而，某些风险和不良事件与运动有关，包括低血糖。最近在成人和儿童人群中的研究表明，无论是保持正常的胰岛素供应、减少胰岛素供应，还是在运动期间完全停止胰岛素供应，患者都会发生即刻和迟发性低血糖事件。此外，目前测试的闭环血糖控制系统仅依赖连续血糖监测仪(CGM)和泵注射反馈，当面临体力活动时，它们的性能会恶化。添加心率作为输入信号将允许这些系统检测并对体育活动做出反应；因此，避免在体育活动期间以及最重要的是在体育活动后的几个小时内发生低血糖。拟议的研究分两个连续的阶段进行，系统工程和临床试验。 因此，我们设计了这项探索性研究，主要有三个目标：(I)将心率作为一种新的代谢信号引入T1 DM胰岛素治疗；(Ii)研究人工胰腺系统在T1 DM患者运动中和运动后的表现；(Iii)以心率作为运动标志物来增强我们目前测试的人工胰腺系统，旨在避免体力活动后的低血糖。我们假设，心率监测的使用将恢复在控制条件下观察到的对低血糖和餐后漂移的保护。具体地说，它将导致(I)减少低血糖的发生；(Ii)偏离正常血糖的血糖目标；(Iii)增加葡萄糖系统的稳定性。 公共卫生相关性：我们的研究意义重大，因为它聚焦于1型糖尿病患者严格控制血糖的主要障碍：体力活动。这项工作的总体目标是了解适度运动对胰岛素活动的影响，并开发新一代血糖控制系统，将心率作为体力活动的指标，并定量告知患者的胰岛素治疗方案。

DESCRIPTION (provided by applicant): The proposed research focuses on the changes in glucose/insulin dynamics in type 1 diabetes mellitus (T1DM) patients during and after exercise and their quantification via metabolic modeling. Once identified and quantified these dynamics can be used to adapt insulin delivery in response to physical activity and therefore avoid under or over estimation of insulin needs. Exercise can be either announced, or detected via heart rate monitoring. Addition of heart rate monitoring would allow to minimize the hypo- and hyperglycemic episodes frequently following over or under compensation for exercise. Such an optimization would be applicable to standard insulin treatment (basal and meal boluses), open loop glycemic control (adaptive basal and bolus patterns), and will be critical in any closed loop applications. Recent advancements in diabetes technology include two rapidly evolving parallel areas: insulin delivery devices (subcutaneous or implanted insulin pumps) and continuous glucose monitors (CGM) recording frequent glucose determinations. Preliminary studies have now demonstrated that these two types of devices can be linked successfully in a closed-loop glucose control system but it remains to be shown how these systems will react to metabolic disturbances not triggered by meals, such as exercise. Physical activity has been widely recognized as an essential element of the treatment of patients with T1DM patients. However, certain risks and adverse events are associated with exercise, including hypoglycemia. Recent studies in both adult and pediatric populations have demonstrated that patients suffered immediate and late onset hypoglycemic events both if insulin delivery was kept normal, was reduced, and when it was completely stopped during exercise. Moreover, currently tested closed loop glucose control systems solely rely on continuous glucose monitors (CGM) and pump injection feedback and their performance deteriorates when challenged with physical activity. The addition of heart rate as an input signal will allow such systems to detect and react to physical activity; therefore avoiding hypoglycemia both during and most importantly in the hours after a bout of physical activity. The proposed study is organized in two consecutive phases, system engineering and a clinical trial. Consequently we designed this exploratory study with three principal goals; (i) introduce heart rate as a new metabolic signal in T1DM insulin treatment; (ii) investigate the performances of an artificial pancreas system during and after exercise in T1DM patients; (iii) augment our currently tested artificial pancreas system using heart rate as an exercise marker, targeting avoidance of hypoglycemia post physical activity. We hypothesize that the use of heart rate monitoring will restore the protection against hypoglycemia and postprandial excursion observed during the control condition. Specifically it will result in (i) reduced occurrence of hypoglycemia; (ii) deviation from a euglycemic glucose target; (iii) increased glucose system stability. PUBLIC HEALTH RELEVANCE: Our study is significant because it focuses on the main impediment to tight glycemic control in type 1 diabetes patients: physical activity. The overall goals of this work is to understand the consequences of moderate exercise on the action of insulin and developing a new generation of glucose control systems that use heart rate as an indicator of physical activity and quantitatively inform the insulin regimen of a patient.