Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis.

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

Pathophysiology of SARS-CoV-2 in Lung of Diabetic Patients.

Novel coronavirus disease (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its impact on patients with comorbidities is clearly related to fatality cases, and diabetes has been linked to one of the most important causes of severity and mortality in SARS-CoV-2 infected patients. Substantial research progress has been made on COVID-19 therapeutics; however, effective treatments remain unsatisfactory. This unmet clinical need is robustly associated with the complexity of pathophysiological mechanisms described for COVID-19. Several key lung pathophysiological mechanisms promoted by SARS-CoV-2 have driven the response in normoglycemic and hyperglycemic subjects. There is sufficient evidence that glucose metabolism pathways in the lung are closely tied to bacterial proliferation, inflammation, oxidative stress, and pro-thrombotic responses, which lead to severe clinical outcomes. It is also likely that SARS-CoV-2 proliferation is affected by glucose metabolism of type I and type II cells. This review summarizes the current understanding of pathophysiology of SARS-CoV-2 in the lung of diabetic patients and highlights the changes in clinical outcomes of COVID-19 in normoglycemic and hyperglycemic conditions.