Clinical Management of Diabetes Mellitus in the Era of COVID-19: Practical Issues, Peculiarities and Concerns

Abstract

The management of patients with diabetes mellitus (DM) in the era of the COVID-19 pandemic can be challenging. Even if they are not infected, they are at risk of dysregulated glycemic control due to the restrictive measures which compromise and disrupt healthcare delivery. In the case of infection, people with DM have an increased risk of developing severe complications. The major principles of optimal care for mild outpatient cases include a patient-tailored therapeutic approach, regular glucose monitoring and adherence to medical recommendations regarding lifestyle measures and drug treatment. For critically ill hospitalized patients, tight monitoring of glucose, fluids, electrolytes, pH and blood ketones is of paramount importance to optimize outcomes. All patients with DM do not have an equally increased risk for severity and mortality due to COVID-19. Certain clinical and biological characteristics determine high-risk phenotypes within the DM population and such prognostic markers need to be characterized in future studies. Further research is needed to examine which subgroups of DM patients are expected to benefit the most from specific antiviral, immunomodulatory and other treatment strategies in the context of patient-tailored precision medicine, which emerges as an urgent priority in the era of COVID-19.

Keywords: antidiabetic drugs; coronavirus disease 2019 (COVID-19); diabetes mellitus; glycemic control; mortality; severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2); severity.

Figure 1

Severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV2) infection activates the immune system, resulting in the secretion of pro-inflammatory cytokines, which mediate: (a) insulin resistance in insulin-sensitive tissues such as the liver, skeletal muscle, adipose tissue and vascular endothelium by inhibiting insulin signal transduction and (b) increased activation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS), enhancing the secretion of cortisol, epinephrine and norepinephrine, which in turn aggravates and sustains insulin resistance. Moreover, SARS-CoV2 infection induces endotheliitis in several organs as a direct consequence of viral involvement and of the host inflammatory response. Increases in glycogenolysis, anaerobic glycolysis and proteolysis in muscle and lipolysis in adipose tissue increase the production of substrates for gluconeogenesis and of non-esterified fatty acids (NEFAs), leading to an increase in hepatic glucose production and blood glucose levels (stress hyperglycemia). Endothelial dysfunction causes vasoconstriction, ischemia and coagulation abnormalities. SARS-CoV2 may directly damage pancreatic β-cells, reducing insulin release. The combination of hyperglycemia, insulin deficiency, the overutilization of NEFAs and dehydration can predispose to the development of diabetic ketoacidosis (DKA) in patients infected with SARS-CoV2. Overactivation of the immune system induces a strong inflammatory response, which can be enormous in critically ill patients (cytokine storm), further activating the HPA axis and ANS, enhancing insulin resistance and metabolic abnormalities.