Bio-Behavioral Feedback and Control of Type 1 Diabetes

描述（由申请人提供）：本提案延续了十年来对生物行为监测方法的研究，该方法已被证明可用于评估1型糖尿病（T1DM），通过采取下一个合乎逻辑的步骤-从监测到反馈。我们计划检验和验证以下一般假设：T1DM患者血糖控制的优化，即维持接近正常的HbA1c而不增加低血糖的风险，几乎完全依赖于两级反馈的质量：(1)外部行为水平定义为患者对症状、认知、低血糖风险和糖化血红蛋白等信息的获取和利用；(2)内部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对行为反馈效用的实地调查（第一阶段）和对胰岛素转移的内部反馈回路的医院实验室调查（第二阶段）和反调节（第三阶段）。具体:

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.