Diabetes Mellitus, a Leading Comorbidity in COVID-19: an Insight on Pathophysiology, Molecular Interactions, and...

Coronavirus disease 2019 (COVID-19) has triggered a global pandemic with widespread disruption. Its mortality rate is notably higher in individuals with coexisting non-communicable diseases, particularly diabetes mellitus (DM). Despite extensive efforts, there remains no definitive treatment for COVID-19, making it imperative to protect populations with pre-existing risk factors that predispose them to severe or fatal outcomes. In this systematic literature review, we delineate the key biological and clinical risk factors-specifically, chronic hyperglycemia, endothelial dysfunction, and dysregulated angiotensin-converting enzyme 2 (ACE2) expression-that may exacerbate COVID-19 severity in diabetic patients. We explore how immune and inflammatory pathways intersect with COVID-19 pathogenesis and contribute to differential clinical manifestations in diabetic versus non-diabetic individuals. Particular emphasis is placed on the pathophysiological mechanisms facilitating viral entry and propagation in diabetic patients. Currently, insulin is the primary therapeutic modality for managing acute hyperglycemia in COVID-19, while sodium-glucose cotransporter 2 (SGLT2) inhibitors are generally discouraged due to potential adverse outcomes. As existing evidence is largely preliminary, further research is essential to establish optimized treatment strategies for this vulnerable patient population.