Could Exogenous Insulin Ameliorate the Metabolic Dysfunction Induced by Glucocorticoids and COVID-19?

Abstract

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.

Keywords: coronavirus – COVID-19; critical-illness; dexamethasone; glucocorticoid; insulin.

Figure 1

Cortisol metabolism. Cortisol is converted in peripheral tissues to cortisone by 11β-hydroxysteroid dehydrogenase (11β-HSD). Cortisone has marginally reduced glucocorticoid activity compared to cortisol (80-90%), and thus, cortisone can be considered an active metabolite of cortisol. Unbound cortisol is biologically active, but the majority of circulating cortisol is bound to corticosteroid-binding globulin (CBG) and albumin. Cortisol is metabolized by 5α- and 5β reductases to form 5α- and 5β-tetrahydrocortisol (5α- and 5β-THF).

Figure 2

Mechanisms of hyperglycaemia during states of stress and inflammation. Stress hyperglycemia is the end result of a neurohumeral and inflammatory process characterized by excessive gluconeogenesis and glycogenolysis and impaired insulin-mediated glucose uptake. Grey arrows: gluconeogenic precursors IL, interleukin; TNF-α, tumour necrosis factor-α; VLDL, very low-density lipoprotein.