Restoring awareness of hypoglycemia in type 1 diabetes

恢复对 1 型糖尿病低血糖的认识

• 批准号: 10598823
• 负责人: Michael R Rickels
• 金额: $ 40.58万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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/10598823
• 关键词: Achievement; Adult; Age; Awareness; Blood Glucose; Carbohydrates; Clinical; Clinical Research; Clinical Trials Design; Closure by clamp; Defect; Defense Mechanisms; Development; Diabetes Mellitus; Disease; Dose; Education; Epinephrine; Event; Exposure to; Failure; Generations; Glucagon; Hepatic; Heterogeneity; Hybrids; Hyperglycemia; Hyperinsulinism; Hypoglycemia; Impairment; Individual; Ingestion; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Islets of Langerhans Transplantation; Lead; Life Experience; Measurement; Measures; Morbidity - disease rate; Outcome; Pancreatic Polypeptide; Participant; Patient Self-Report; Peripheral; Pharmacology; Physiological; Questionnaires; Randomized; Randomized Clinical Trials; Reporting; Research Design; Risk; Sequential Multiple Assignment Randomized Trial; Standardization; Symptoms; Syndrome; System; Technology; Testing; Therapeutic; Time; Work; clinical practice; counterregulation; experience; falls; glucose disposal; glucose monitor; glucose production; glycemic control; illness length; improved; insulin secretion; mortality; novel; personalized approach; personalized intervention; post-transplant; response; restoration; standard of care; theories; trial design

PROJECT SUMMARY / ABSTRACT This application “Restoring awareness of hypoglycemia in type 1 diabetes” proposes to elucidate the heterogeneity of impaired awareness of hypoglycemia (IAH) in type 1 diabetes through completion of a 24-month Sequential Multiple Assignment Randomized Trial (SMART) designed to better inform our understanding of the clinical and physiologic factors which contribute to restoration of counterregulatory defenses against hypoglycemia in response to educational, technologic, and pharmacologic interventions. Given the persistent barrier of hypoglycemia to the realization of achieving adequate glycemic control for most individuals with type 1 diabetes, there is a critical need to further understand the mechanisms contributing to hypoglycemia in type 1 diabetes in order to advance treatment approaches that may realize the benefits of near-normal glycemic control without the accompanying risk for severe hypoglycemia. The present proposal aims 1) to determine whether counterregulatory responses to a hyperinsulinemic hypoglycemic clamp can be restored in individuals with long standing type 1 diabetes and IAH using an adaptive randomized clinical trial design implementing state-of-the- art interventions including hypoglycemia avoidance education (standard-of-care; SOC), automated insulin delivery with hybrid closed loop technology (HCL), and novel mini-dose glucagon (MDG) pharmacology; 2) to determine the physiological factors associated with improved counterregulatory responses following intervention, including but not limited to age, diabetes duration, and continuous glucose monitoring (CGM) metrics; and 3) to validate a HypoA-Q short form questionnaire as a self-report measure for identifying IAH with measurement of counterregulatory responses derived from the hypoglycemic clamp. The proposed SMART study design will allow for rigorously determining both the degree of hypoglycemia avoidance necessary for improvement of counterregulatory epinephrine and autonomic symptom responses to insulin-induced hypoglycemia, as well as the additional factors such as age, diabetes duration, other CGM metrics, and validated IAH self-report that may predict individual responsiveness to SOC, HCL, and MDG interventions.

项目总结/摘要 本申请“恢复对1型糖尿病低血糖症的认识”提出阐明 1型糖尿病患者低血糖意识受损（IAH）的异质性 序贯多重分配随机试验（SMART）旨在更好地了解 有助于恢复反调节防御的临床和生理因素， 教育、技术和药物干预后的低血糖。鉴于持续的 低血糖障碍，以实现充分的血糖控制，为大多数个人的类型 1型糖尿病，有一个关键的需要，以进一步了解机制，有助于低血糖症的1型 糖尿病，以推进可能实现接近正常血糖控制益处的治疗方法 而不伴随严重低血糖的风险。本提案旨在：（1）确定是否 对高胰岛素低血糖钳夹的反调节反应可以在患有长期高胰岛素低血糖钳夹的个体中恢复。 采用适应性随机临床试验设计， ART干预，包括低血糖避免教育（标准治疗; SOC）、自动胰岛素 采用混合闭环技术（HCL）和新型小剂量胰高血糖素（MDG）药理学进行递送; 2） 确定与干预后改善的反调节反应相关的生理因素， 包括但不限于年龄、糖尿病持续时间和连续葡萄糖监测（CGM）度量;以及3） 验证HypoA-Q简表问卷作为识别IAH的自我报告措施， 来自低血糖钳夹的反调节反应。拟议的SMART研究设计将 允许严格确定改善低血糖所需的低血糖避免程度， 反调节肾上腺素和自主神经症状对胰岛素诱导的低血糖的反应，以及 其他因素，如年龄、糖尿病病程、其他CGM指标和经验证的IAH自我报告， 预测个体对SOC、HCL和MDG干预措施的反应。