Figure 3.

T2DM is a progressive disease with multiple stages and phases in humans. At the time of diagnosis of T2DM, patients may already have a 50% reduction in β-cell function. As one moves through the various stages/phases, there is a progressive loss of β-cell function, while concurrently there is increased deposition of amylin-derived islet amyloid and islet fibrosis (islet remodeling—isletopathy). When SARS-CoV-2 (spiked icon) binds to the ACE2 receptor of β-cells and vascular EC/pericyte, cells there will be a detrimental increase in the ratio of the ANG II–ACE2–MasR axis. COVID-19 is known to be associated with a systemic and even local cytokine storm in addition to a redox storm (excessive oxidative stress—reactive oxygen and nitrogen (nitrosative stress) species (RONS)) and could be possibly based on the viral virion (viral load) storm associated with viremia. Therefore, COVID-19 could accelerate the natural history of T2DM. This image is based on a classic graph by Lebovitz HE. Diabetes Rev. 1999, 7, 139–153 and Hayden MR et al. JOP. J. Pancreas (online) 2002, 3(5), 126–138. BM = basement membrane; CoV-2 = abbreviation of SARS-CoV-2; EC = endothelial cell; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; ISG = insulin secretory granule; MetS = metabolic syndrome; T2DM = type 2 diabetes mellitus.