COVID-19 and diabetes

Conditions associated with increased morbidity and mortality in individuals infected with SARS-CoV-2 are the presence of diabetes, hypertension, cardiovascular disease, and severe obesity. Considering the high prevalence of hypertension, cardiovascular disease, and obesity in individuals with diabetes, it is difficult to know how diabetes alone directly contributes to the increased risk of adverse outcomes following SARS-CoV-2 infection. Studies indicate that 12–16% of individuals with severe infections have diabetes. A meta-analysis of six clinical studies involving 1,687 COVID-19 patients provided evidence that individuals with diabetes exhibited a similar prevalence of being infected with SARS-CoV-2 as the overall population, but presence of diabetes was a critical comorbidity that increased the risk of a poor outcome. Factors that may complicate COVID-19 in individuals with diabetes include 1) the presence of bone marrow changes (myeloidosis) that predispose those with diabetes to an excessive proinflammatory response (cytokine storm) and contribute to insulin resistance and reduced vascular repair, and worsening function of the heart, kidney, and systemic vasculature as a whole; 2) increased circulating furin levels that could cleave the spike protein and increase infectivity of SARS-CoV-2; 3) dysregulated autophagy that may promote replication and/or reduce viral clearance; and 4) gut dysbiosis that leads to widespread systemic inflammation, increased gut glucose and sodium absorption, and reduced tryptophan and other key amino acid absorption needed for incretin secretion and glucose homeostasis. Central to each of these dysfunctions is the dysregulated RAS, in particular, the global loss of ACE2, which is proposed as a unifying mechanism that could lead to the increased risk of morbidity and mortality in individuals with diabetes presenting with COVID-19. A dysregulated renin-angiotensin system (RAS), as seen in diabetes, could lead to an increase in serum levels of angiotensin II (Ang-II) that could cause a plethora of potentially harmful effects including vasoconstriction, inflammation, and increased oxidative stress. (PMID: 32669391)

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