Characterizing the evolution of impaired hypoglycemia awareness in people with type 1 diabetes and the impact of automated insulin delivery and exercise on restoring hypoglycemia awareness

描述 1 型糖尿病患者低血糖意识受损的演变以及自动胰岛素输送和运动对恢复低血糖意识的影响

• 批准号: 10599031
• 负责人: Tim Jones
• 金额: $ 27.08万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-25 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599031
• 关键词: Adolescence; Adrenergic Agents; Adult; Adverse effects; Affect; American; Awareness; Benchmarking; Carbohydrates; Child; Childhood; Closure by clamp; Communities; Complications of Diabetes Mellitus; Data; Defect; Diabetes Mellitus; Dose; Education; Eligibility Determination; Epinephrine; Evolution; Exercise; Family; Fright; Funding; Glucagon; Glucose; Gold; Hormones; Hypoglycemia; Immunosuppression; Impairment; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Islets of Langerhans Transplantation; Knowledge; Lead; Manuals; Modernization; Outcome; Participant; Pediatric cohort; Persons; Productivity; Randomized; Randomized Controlled Trials; Recurrence; Reporting; Research; Resources; Risk; Role; Site; Societies; Structure; Symptoms; Syndrome; System; Technology; Time; Well in self; blood glucose regulation; cohort; effective intervention; exercise program; glucose monitor; glucose production; high risk; improved; insight; mortality; new technology; population based; preservation; primary outcome; programs; psychoeducation; psychological outcomes; response; restoration; success; tool; treatment as usual

Abstract Impaired hypoglycemia awareness (IAH) affects 25% of adults with type 1 diabetes and is associated with a six-fold higher risk of severe hypoglycemia. Those severely affected have an estimated mortality of 3.4%. IAH is characterized by defects in adrenergic symptoms and the counter-regulatory hormone response to hypoglycemia. Only limited data are available regarding the evolution of IAH. To date, strategies to restore hypoglycemia awareness have focused upon minimizing hypoglycemia exposure. While islet-cell transplantation has met with success, this approach is reserved for only the most severely affected as it is invasive, has strict eligibility criteria, requires long-term immunosuppression and is resource-intensive. So far interventions incorporating education and technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID), have had limited success, though studies have been small and of short duration. We hypothesize that IAH evolves over many years, promoted by recurrent hypoglycemia. In the absence of restoration of a glucagon response, IAH reversal may require an extended period of near-absolute hypoglycemia avoidance. We also hypothesize that high intensity interval exercise (HIIT), which elicits a counter-regulatory hormone response, even in those with severe IAH, may have an adjunctive role in the restoration of hypoglycemia awareness. We propose a randomized-controlled trial in a cohort of adults with type 1 diabetes with IAH using manual insulin dosing. All will be provided with hypoglycemia recognition and avoidance psycho-education. Participants (n=500 in total with 50 studied at our site) will be randomized to 2-years of insulin delivery using the most advanced AID system available with and without adjunctive support for an HIIT program, which will be compared with usual care. The primary outcome will be a composite of sympathetic symptoms and the endogenous glucose production (EGP) response during hypoglycemic clamp studies. Other outcomes are (i) counter-regulatory responses during clamp studies; (ii) percent time in CGM low- glucose ranges in real-world conditions; and (iii) person reported outcomes, including hypoglycemia awareness symptom scores. Type 1 diabetes cohorts without IAH and those who have had a successful islet-transplant will be studied at a single time-point to provide positive control data. In addition, we will follow a population-based pediatric cohort of over 1000 children, with 93% using CGM. Changes in CGM low glucose time will be related to changes in Gold and Clarke scores over 4-years, with potential to extend this with separate funding. Data from this program of research will substantially advance knowledge of IAH and guide practical and meaningful interventions.

抽象的 低血糖意识受损（IAH）会影响1型糖尿病的成年人的25％，并且与 严重低血糖症的风险高六倍。受到严重影响的人的死亡率估计为3.4％。 IAH的特征是肾上腺素能症状的缺陷以及对 低血糖。关于IAH的演变，只有有限的数据。迄今为止，恢复策略 低血糖意识的重点是最大程度地减少低血糖暴露。而胰岛细胞 移植成功，这种方法仅用于最严重影响的，因为它是 侵入性，具有严格的资格标准，需要长期的免疫抑制，并且是资源密集的。所以 包括持续的葡萄糖监测，包括教育和技术的远方​​干预措施 （CGM）和自动胰岛素输送（AID）的成功有限，尽管研究很小 持续时间很短。我们假设IAH多年来演变，以经常性促进 低血糖。在没有胰高血糖素反应的恢复的情况下，IAH逆转可能需要延长 避免了近乎吸毒的低血糖时期。我们还假设高强度间隔运动 （HIIT），即使在患有严重IAH的患者中，也会引起反调节激素的反应 在恢复低血糖意识中的辅助作用。 我们在使用手动的1型糖尿病的成年人中提出了一项随机控制的试验 胰岛素给药。所有这些都将获得低血糖识别和回避心理教育。 参与者（在我们的网站上总共有50个研究的参与者）将被随机分为2年的胰岛素输送 使用最先进的援助系统，没有辅助支持HIIT程序， 将与通常的护理进行比较。主要结果将是同情的综合 在降血糖夹研究期间，症状和内源性葡萄糖产生（EGP）反应。 其他结果是（i）夹具研究期间的反调节反应； （ii）CGM低 - 在现实世界中的葡萄糖范围； （iii）人报告的结果，包括低血糖 意识症状得分。 1型糖尿病队长没有IAH和那些成功的人 胰岛移植将以单个时间点进行研究，以提供积极的对照数据。此外，我们将 遵循以人群为基础的儿科队列，其中1000多名儿童，使用CGM 93％。 CGM的变化 低葡萄糖时间将与4年以上黄金和克拉克分数的变化有关，并有可能扩展 这是单独的资金。 该研究计划的数据将大大提高IAH知识，并指导实用和 有意义的干预措施。