University of Minnesota Clinical Center for the Restoration of Impaired Awareness of Hypoglycemia in Type 1 Diabetes

低血糖（HG）在1型糖尿病（T1 D）患者的生活中很常见，并可能阻止他们 实现与最佳血糖控制相关的益处。复发性HG持续数天至数周， 导致HG（IAH）意识受损的状况，其中低血糖的第一个迹象是混乱，或 昏迷避免HG与IAH风险降低相关，如果严格执行，可能会恢复HG 在一些但不是所有的IAH患者中。这种反应不一致的原因仍然不确定。 本申请的目的是申请成为一个联盟的一部分，该联盟将实施一个协议，该协议旨在 恢复T1 D和IAH患者对HG的认识。根据FOA的指示，我们解决以下问题 我们的应用目标： 1.确定是否使用最新的T1 D和IAH管理策略进行糖尿病护理。 2.确定与HG意识恢复相关的生理因素，包括但不限于 仅限于年龄、糖尿病持续时间和糖尿病指标。 3.确定当前自我报告问卷的关联（或开发新的问卷， 指标）用于使用“最先进的”代谢评估通过CRR测量来鉴定IAH。 为了达到目标1，我们建议联盟招募650名T1 D和IAH受试者进入随机临床试验， 一项为期12个月的HG避免教育干预和使用胰岛素混合闭环系统的试验 将输注与标准护理（其包括HG避免教育、通过常规的胰岛素给药、胰岛素输注和胰岛素输注）进行比较。 泵或注射以及CGM使用）。12个月时低血糖钳夹期间肾上腺素反应 作为我们的主要结果变量，我们将检验闭环干预中的受试者 在12个月的随访中，在低血糖钳夹期间，手臂将具有更大的肾上腺素反应- 比对照组的受试者要高。 为了实现目标2，我们将收集有关血糖变异性、食物质量和数量、身体状况、 活动、睡眠、压力、情绪和对HG的感觉以及患者特征，如HG诱导的 胰高血糖素分泌、残余C肽分泌和糖尿病持续时间。这些信息将被探索。 使用机器学习技术来了解哪些暴露和体验与IAH恢复相关。 为了达到目标三，我们将比较Clarke、Gold和Hypo-AQ问卷的一致性， 将受试者分为IAH组和NAH组。每一份调查问卷的分数也将相互关联 对反监管反应的客观衡量。

Hypoglycemia (HG) is common in the lives of people with type 1 diabetes (T1D) and may prevent them from achieving the benefits associated with optimal glycemic control. Recurrent HG over a few days to weeks may lead to the condition of impaired awareness of HG (IAH) where the first sign of a low blood sugar is confusion or unconsciousness. Avoiding HG is associated with a reduced risk of IAH and when strictly done, may restore HG in some but not all patients with IAH. The reason for this heterogeneity in response remains uncertain.The purpose of this application is to apply to become part of a consortium that will implement a protocol designed to restore awareness of HG in persons with T1D and IAH. As instructed by the FOA, we address the following objectives in our application: 1. Determine if diabetes care with use of the most up-to-date management strategies with T1D and IAH. 2. Determine the physiological factors that are associated with restoration of HG awareness, including but not limited to age, duration of diabetes and metrics of glycemia. 3. Determine the association of the current self-report questionnaires (or develop new questionnaires or metrics) for identification of IAH with measurement of CRR using "state of the art" metabolic assessments. To meet objective 1, we propose the consortium enroll 650 subjects with T1D and IAH into a randomized clinical trial where a 12-month intervention of HG avoidance education and use of a hybrid closed loop system for insulin infusion is compared to standard care (which includes HG avoidance education, insulin administration via regular pump or injections, and CGM usage). With epinephrine response during the hypoglycemic clamp at 12 months as our primary outcome variable, we will test the hypothesis that subjects in the closed loop intervention arm will have a greater epinephrine response during the hypoglycemic clamp at 12 months of follow- up than will subjects in the control arm. To meet objective 2, we will collect information about glycemic variability, food quality and quantity, physical activity, sleep, stress, mood, and feelings about HG as well as patient characteristics such as HG induced glucagon secretion, residual C-peptide secretion, and diabetes duration. This information will then be explored using machine learning techniques to see what exposures and experiences correlate with IAH restoration. To meet objective three, we will compare the concordance of the Clarke, Gold, and Hypo-AQ questionnaires at categorizing subjects into IAH and NAH groups. The scores on each of the questionnaires will also be correlated with objective measures of the counterregulatory response.