COVID-19 and diabetes mellitus: from pathophysiology to clinical management

Abstract

Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin–angiotensin–aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium–glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.

Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

“…The available data are interpreted through a lens focusing on gaps and limitations, often precluding definitive conclusions. Readers are referred to earlier reviews that predominantly address clinical and therapeutic guidance ( Bornstein et al., 2020 ; Drucker, 2020 ; Lim et al., 2021 ).…”

The MERS-CoV receptor gene is among COVID-19 risk factors inherited from Neandertals

“…It is involved in several physiological systems, including the regulation of glucose metabolism (Mentlein, 1999). Inhibitors of DPP4 are used to treat diabetes and have been suggested to affect COVID-19 outcomes in preliminary studies (reviewed in Lim et al 2021).…”

Could targeting immunometabolism be a way to control the burden of COVID-19 infection?

“…The hyperglycemia, characteristic of diabetes, is made worse by Covid-19 infection and many patients require more insulin to control their disease [ 53 ]. In some instances, Covid-19 infection may actually trigger the onset of diabetes [ 54 ], although whether or not this is a direct consequence of virus infection, or a secondary consequence of inflammatory events, is not clear [ 54 ]. Obesity, which is a common clinical problem in diabetes, is discussed in a different section of this review.…”