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

描述（由申请人提供）：拟研究1型糖尿病（T1DM）患者运动期间和运动后葡萄糖/胰岛素动力学的变化，并通过代谢模型对其进行量化。一旦确定并量化了这些动态，就可以根据身体活动来调整胰岛素输送，从而避免胰岛素需求的低估或高估。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减少低血糖和高血糖发作，经常在过度或不足的补偿运动。这种优化将适用于标准胰岛素治疗（基础和餐丸），开环血糖控制（自适应基础和餐丸模式），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（皮下或植入胰岛素泵）和连续血糖监测仪（CGM）记录频繁的血糖测定。目前的初步研究表明，这两种类型的设备可以成功地连接在一个闭环葡萄糖控制系统中，但这些系统如何对非膳食引发的代谢紊乱（如运动）做出反应仍有待研究。体育活动已被广泛认为是治疗T1DM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。最近对成人和儿童人群的研究表明，如果胰岛素输送保持正常，减少，以及在运动中完全停止，患者都会出现立即和晚发性低血糖事件。此外，目前测试的闭环血糖控制系统仅依赖于连续血糖监测仪（CGM）和泵注射反馈，当受到身体活动的挑战时，其性能会下降。增加心率作为输入信号将使此类系统能够检测身体活动并作出反应；因此，避免低血糖，尤其是在一次体育活动期间和之后的几个小时。该研究分为两个连续的阶段，系统工程和临床试验。

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.