Shared pathways for COVID-19 and diabetes?

The idea that COVID-19 and diabetes have shared pathways stems from the fact that medications used to treat diabetes often include agents that modulate the expression and activity of angiotensin converting enzyme 2 (ACE2), a key player in SARS-CoV-2 infectivity. Despite new insights, the effects of possible shared pathways remain unclear [1].

ACE2 is the principal receptor through which SARS-CoV-2 enters cells, and the cellular protease, TMPRSS2, enables this entry through priming of the spike protein. In addition, no entry of SARS-CoV-2 has been observed in the absence of dipeptidyl peptidase-4 (DPP-4), as DPP-4 is permissive for entry of the virus. Regarding DDP-4 inhibitors, there is no clear evidence in patients with COVID-19 and type 2 diabetes that these agents are beneficial. Data has shown that they can reduce inflammation, but a recent analysis of the TECOS trial in which patients were treated with sitagliptin, showed no change in the inflammatory biomarkers, CRP, IL-6, and TNF-α. The use of metformin in the TECOS trial, however, significantly reduced inflammation. In people with COVID-19 who are using metformin, an increased risk was seen for ketoacidosis, although this did not affect mortality. Observational data also suggested that people taking statins may experience improved COVID-19 outcomes in the hospital. Diabetics taking insulin had a higher risk of morbidity and mortality from the virus, but this may result from comorbidities associated with diabetes. The question remains as to whether SARS-CoV-2 can infect insulin-producing beta cells causing insulin deficiency and onset of type 1 diabetes. ACE2 and TMPRSS2 are expressed on endothelial cells in the ducts of the pancreas and CoV-2 may attack them. It was concluded that in patients with COVID-19 and type 2 diabetes, optimising glycaemic control was most important.

1. Drucker DJ. COVID-19 and type 2 diabetes: Do shared pathways have therapeutic implications? EASD 2020. Session: COVID-19 and diabetes.

Posted on 14 December, 202016 December, 2020