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

项目摘要/摘要 这一建议检验了新的假设，即先前存在的糖尿病(或新的应激性高血糖)会加剧 新冠肺炎介导的微血管损伤及其持续性对修复的影响 高血糖和糖尿病相关的持续性内皮损伤。我们的长期目标是了解 新冠肺炎感染对糖代谢和糖尿病的影响 并发症。胰岛和骨骼肌的有效灌注量减少可能是导致后 新冠肺炎感染的后遗症，如胰岛素分泌减少、胰岛素作用减弱和乏力等。 这项建议的目的是研究新冠肺炎感染对人的短期影响。 住院期间碳水化合物与骨骼肌代谢的相关性检验 这些晚期终点出现高血糖和弥漫性内皮损伤。 假设：新冠肺炎有害影响碳水化合物代谢和骨骼肌功能 由于全身血流灌注异常，糖尿病患者情况更糟；这些患者住院后恢复 在高血糖和内皮损伤的情况下，参数会变慢。 SA#1：检验新冠肺炎损害胰岛素分泌和作用的假设，以及 在持续性高血糖和/或弥漫性内皮细胞的情况下，住院恢复缓慢 受伤。胰岛素分泌减少与全身性胰岛素抵抗对新冠肺炎的相对贡献 介导性高血糖以及引起血糖异常的因素尚不清楚。在这一目标下的研究将 评价人弥漫性内皮损伤和血糖异常与糖代谢的关系 用口服葡萄糖耐量试验检测糖尿病患者入院后是否患有糖尿病。 SA#2：测试血糖异常和弥漫性内皮损伤减缓骨骼肌损伤的假设 新冠肺炎后恢复。目前还没有关于新冠肺炎功能状态恢复后或骨骼肌的数据 比较糖尿病患者和非糖尿病患者的功能。这些实验将检查住院后的情况 肌肉氧化通量、胰岛素作用和灌注量及其与血糖的相关性 新冠肺炎住院后糖尿病患者和非糖尿病患者的概况和内皮损伤。 影响：拟议研究的成功执行将提供有关从COVID中恢复的新信息- 19关于碳水化合物代谢和脆弱。这些数据可能会提示入院后的血糖 减少新冠肺炎对糖尿病患者的长期后果的管理。

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.