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.

R01DK130351

2021-09-15

2024-08-31