Bio-Behavioral Feedback and Control of Type 1 Diabetes

描述（由申请人提供）：该提案继续了对生物行为监测方法的十年研究，该方法已被证明可用于评估1型糖尿病（T1 DM），并采取了下一个逻辑步骤-从监测到反馈。我们计划测试和验证以下一般假设：T1 DM患者血糖控制的优化，即维持接近正常的HbA 1c而不增加低血糖风险，几乎完全取决于两个级别反馈的质量：（1）外部行为水平，定义为患者对有关症状、意识、低血糖风险和HbA 1c的信息的可用性和利用，（2）内分泌系统水平，定义为微血管募集、激素反调节和胰岛素-葡萄糖相互作用的反馈网络。因此，拟议的研究计划包括行为反馈效用的实地调查（第1阶段）和胰岛素传递（第2阶段）和反调节（第3阶段）的内部反馈回路的医院实验室调查。具体而言： 第1阶段将创建一个综合生物行为监测和反馈（IBMF）系统，并将在T1 DM患者自然环境中的现场结果研究中研究其改善血糖控制的临床效用，假设T1 DM的日常行为控制取决于4个连续步骤的质量：监测->评估->患者反馈->行为优化。 II期将在I期确定的低血糖低风险与高风险的T1 DM受试者中，使用胰岛素诱导微血管募集和随后胰岛素通过毛细血管内皮转运的随机过程模型，研究胰岛素从循环转移到肠组织的时间过程。 III期研究将使用动态网络模型研究在I期研究中确定的低血糖低风险与高风险T1 DM受试者中低血糖相关自主神经功能衰竭（HAAF）的发展时间进程和动态特征。 将II期和III期的结果转移到I期，我们将阐明：（1）胰岛素敏感性和HAAF对现场复发性低血糖风险的相对贡献，以及（2）IBMF逆转HAAF和降低低血糖风险的能力，从而有助于改善血糖控制。

DESCRIPTION (provided by applicant): This proposal continues ten years of research on biobehavioral monitoring methods with proven utility to the assessment of Type 1 diabetes (T1DM), by taking the next logical step - from monitoring to feedback. We plan to test and validate the following general hypothesis: The optimization of glycemic control in T1DM, i.e. the maintenance of near-normal HbA1c without increasing the risk of hypoglycemia, is almost entirely dependent on the quality of two levels of feedback: (1) External behavioral level defined as the availability and utilization by patients of information about symptoms, awareness, risk of hypoglycemia, and HbA1c, and (2) Internal endocrine system level defined as the feedback networks of microvascular recruitment, hormonal counter regulation, and insulin-glucose interaction. Consequently, the proposed research plan includes field investigation of the utility of behavioral feedback (Phase 1) and hospital laboratory investigations of the internal feedback loops of insulin transfer (Phase 2) and counter regulation (Phase 3). Specifically: Phase 1 will create an Integrated Biobehavioral Monitoring and Feedback (IBMF) system and will investigate its clinical utility to improve glycemic control in a field outcomes study of T1 DM patients in their natural environment, assuming that the everyday behavioral control of T1DM depends on the quality of 4 sequential steps: monitoring -> assessment -> feedback to the patient -> behavioral optimization. Phase 2 will investigate, in T1DM subjects at low vs. high risk for hypoglycemia as determined in Phase 1, the time course of insulin transfer from circulation to iterstitium using a stochastic process model of insulin-induced microvascular recruitment and subsequent insulin transport through the capillary endothelium. Phase 3 will use a dynamical network model to investigate the time course of development, and the dynamical characteristics of hypoglycemia-associated autonomic failure (HAAF) in T1DM subjects at low vs. high risk for hypoglycemia as determined in Phase 1. Transferring the results from Phases 2 and 3 into Phase 1 we will clarify: (1) the relative contribution of insulin sensitivity and HAAF to risk for recurrent hypoglycemia in the field, and (2) the ability of IBMF to reverse HAAF and reduce risk of hypoglycemia, thereby contributing to improved glycemic control.