COVID-19, Hyperglycemia, and New-Onset Diabetes

Abstract

Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the b-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in the clinical disease coronavirus disease 2019 (COVID-19) was first reported in December 2019 Wuhan, China, and has claimed over 2 million lives globally (1). Certain chronic comorbidities, such as hypertension, cardiovascular disease, obesity, diabetes, and kidney disease, are highly prevalent in people with COVID-19. While these comorbidities do not appear to increase the risk of developing COVID-19, they are associated with an increased risk of a more severe case of the condition as well as mortality (2).

Hyperglycemia and insulin resistance in COVID-19 versus non-COVID critical illness: Are they really different?

“…Hyperglycemia frequently develops in patients with severe COVID-19, regardless of preadmission diabetes status, as in non-COVID critically ill patients [ 1 , 2 ]. In non-COVID patients, stress hyperglycemia has been attributed to insulin resistance due to elevated counterregulatory hormones, cytokines, and drugs including steroids, although beta-cell dysfunction through prolonged hyperglycemia, poor beta-cell reserve, hypoperfusion and inflammation may co-exist in some patients (Fig.…”

“…1 ) [ 3 ]. As in non-COVID patients, numerous observational studies have associated more severe hyperglycemia and increased glucose variability with poor outcome in COVID-19 patients [ 1 , 2 , 4 , 5 ]. However, causality remains unclear, since insulin resistance and resultant hyperglycemia closely relate to illness severity [ 1 , 6 ].…”

“…1 ) [ 8 – 11 ], which could predispose COVID-19 patients to diabetic emergencies. On the other hand, patients with severe COVID-19 more commonly have pre-existing diabetes and/or increased body-mass index as risk factors for insulin resistance, which is aggravated by routine steroid treatment [ 2 , 12 ]. Clinical evidence confirming an increased incidence of diabetic emergencies related to COVID-19 surges is inconsistent, as are mechanistic studies on potential virus-induced alterations in glucose homeostasis [ 2 , 8 – 11 ].…”

“…However, apart from the low number of included patients, several issues warrant caution not to overinterpret these findings, including the suboptimal tissue quality due to autolysis, conflicting data regarding the pancreatic expression of SARS-CoV-2 receptors and the beta-cell selectivity of viral damage, and the lack of in vivo evidence [ 8 – 10 ]. If virus-mediated beta-cell death would be a primary mechanism of hyperglycemia in severe COVID-19, one would expect persistent insulin need in the majority of patients, which is not the case [ 2 ]. Whether COVID-19 associates with an increased incidence of persistent diabetes mellitus or not, is currently being investigated [ 2 ].…”

“…If virus-mediated beta-cell death would be a primary mechanism of hyperglycemia in severe COVID-19, one would expect persistent insulin need in the majority of patients, which is not the case [ 2 ]. Whether COVID-19 associates with an increased incidence of persistent diabetes mellitus or not, is currently being investigated [ 2 ]. Interestingly, a recent mechanistic study found potentially reversible beta-cell transdifferentiation rather than cell death in human islets exposed to SARS-CoV-2, characterized by lower expression of insulin and upregulated expression of alpha-cell markers [ 10 ].…”