Impact of SARS CoV2 on post-hospital recovery of carbohydrate and muscle metabolism: role of endothelial injury

SARS CoV2 对出院后碳水化合物和肌肉代谢恢复的影响：内皮损伤的作用

• 批准号: 10319430
• 负责人: JANE E REUSCH
• 金额: $ 39.86万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319430
• 关键词: 2019-nCoV; Address; Architecture; Beta Cell; Blood capillaries; Blood flow; COVID-19; COVID-19 mortality; Carbohydrates; Cardiovascular Diseases; Complications of Diabetes Mellitus; Data; Diabetes Mellitus; Diffuse; Endothelium; Fatigue; Functional disorder; Future; Glucose; Goals; Hospitalization; Hospitals; Hyperglycemia; Hypertension; Impairment; Infection; Injury; Inpatients; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intervention Studies; Islets of Langerhans; Measures; Mediating; Microcirculation; Microvascular Dysfunction; Modeling; Muscle; Muscle Mitochondria; Muscle Weakness; Muscle function; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Organ; Outpatients; Perfusion; Predisposition; Questionnaires; Recovery; Rehabilitation therapy; Reporting; Role; SARS-CoV-2 infection; Sepsis; Skeletal Muscle; Specific qualifier value; Stress; Testing; Therapeutic; Time; carbohydrate metabolism; comorbidity; endothelial dysfunction; experimental study; frailty; functional status; glucose monitor; in vivo; insulin secretion; intravital microscopy; islet; mathematical model; mortality; mortality risk; multidisciplinary; muscle metabolism; novel; primary endpoint; rehabilitation strategy; secondary analysis; severe COVID-19; skeletal muscle metabolism

Project Summary/Abstract This proposal tests the novel hypothesis that pre-existing diabetes (or new stress hyperglycemia), exacerbates the systemic impact of COVID-19-mediated microvascular injury and slows recovery via persistence of hyperglycemia and diabetes related persistent endothelial injury. Our long-term goal is to understand the post-infection consequences of COVID-19 infection on carbohydrate metabolism and diabetes complications. Decreased effective perfusion of the islets and skeletal muscle may contribute to the post- infection sequelae of COVID-19 infection such as decreased insulin secretion and insulin action and fatigue. The goal of this proposal is to examine the short-term impact of COVID-19 infection on post- hospitalization carbohydrate and skeletal muscle metabolism, and to test the correlation of hyperglycemia and diffuse endothelial injury with these late endpoints. Hypothesis: COVID-19 deleteriously impacts carbohydrate metabolism and skeletal muscle function due to systemic perfusion abnormalities, worse in diabetes; post-hospitalization recovery of these parameters will be slowed in the context of hyperglycemia and endothelial injury. SA#1: Test the hypothesis that COVID-19 impairs insulin secretion and action and that post- hospitalization recovery is slowed in the context of persistent hyperglycemia and/or diffuse endothelial injury. The relative contribution of decreased insulin secretion versus systemic insulin resistance to COVID-19 mediated hyperglycemia is unknown, as are the factors contributing to dysglycemia. Studies under this aim will evaluate the relationship of diffuse endothelial injury and dysglycemia to carbohydrate metabolism in people with and without diabetes post-hospitalization using an oral glucose tolerance test. SA# 2: Test the hypothesis that dysglycemia and diffuse endothelial injury slow skeletal muscle recovery post COVID-19. No data exist on post COVID-19 functional status recovery or skeletal muscle function comparing people with and without diabetes. These experiments will examine post-hospitalization muscle oxidative flux, insulin action and perfusion and explore the correlation of these parameters, glucose profiles and endothelial injury in people with and without diabetes post COVID-19 hospitalization. Impact: Successful execution of the proposed studies will provide new information on recovery from COVID- 19 with regards to carbohydrate metabolism and frailty. These data may inform post-hospitalization glycemic management to lessen the long-term consequences of COVID-19 in people with diabetes.

项目摘要/摘要 该建议检验了预先存在的糖尿病（或新的压力高血糖），加剧的新假设 共证介导的微血管损伤和通过持久性恢复的系统影响 高血糖和糖尿病相关的持续内皮损伤。我们的长期目标是了解 COVID-19感染对碳水化合物代谢和糖尿病的感染后后果 并发症。胰岛和骨骼肌的有效灌注减少可能有助于后 COVID-19感染的感染后遗症，例如胰岛素分泌减少和胰岛素作用和疲劳。 该提案的目的是检查COVID-19感染对后期的短期影响 住院碳水化合物和骨骼肌代谢，并测试 这些晚期终点高血糖和弥漫性内皮损伤。 假设：COVID-19有害影响碳水化合物的代谢和骨骼肌功能 由于全身性灌注异常，糖尿病患者恶化；这些院后恢复 在高血糖和内皮损伤的背景下，参数将减慢。 SA＃1：检验COVID-19损害胰岛素的分泌和作用的假设，以及后 在持续性高血糖和/或弥漫性内皮的背景下，住院的恢复会减慢 受伤。胰岛素分泌减少与全身性胰岛素耐药性对Covid-19的相对贡献 介导的高血糖尚不清楚，导致血糖症的因素也是如此。在这个目标下的研究将 评估弥漫性内皮损伤和血糖与碳水化合物代谢的关系 使用口服葡萄糖耐受性测试，有和没有糖尿病后院后。 SA＃2：检验低血糖和弥漫性内皮损伤缓慢骨骼肌的假设 恢复后Covid-19。在COVID-19的功能状态恢复或骨骼肌上不存在数据 比较患有和没有糖尿病的人的功能。这些实验将检查院后化 肌肉氧化通量，胰岛素作用和灌注并探索这些参数的相关性，葡萄糖 COVID-19医院后有或患有糖尿病患者的特征和内皮损伤。 影响：拟议的研究的成功执行将提供有关从COVID恢复的新信息 19关于碳水化合物的代谢和脆弱。这些数据可能会为院后血糖提供信息 管理层可以减少Covid-19对糖尿病患者的长期后果。