Dissecting the interaction between COVID‐19 and diabetes mellitus

Abstract

Coronavirus disease 2019 (COVID‐19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus‐2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID‐19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin–angiotensin–aldosterone system inhibitors with COVID‐19. Suggested recommendations for the use of antidiabetic medications for COVID‐19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID‐19 patients. In addition, we aim to increase clinicians’ awareness of the metabolic effects of promising drug therapies for COVID‐19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.

Risk indicators associated with in-hospital mortality and severity in patients with diabetes mellitus and confirmed or clinically suspected COVID-19

“…Accumulation of advanced glycation end products (AGEs) and activation of pro-inflammatory mediators reduce the activity of neutrophils and macrophages, resulting in facilitated pathogen replication [ 28 ]. Overall, DM is associated with reduced viral clearance, immune dysfunction, and increased susceptibility to inflammation [ 29 ]. Consistent with this concept, in a meta-analysis of 83 studies, Mantovani A, et al [ 13 ] reported that patients with DM and COVID-19 had a significantly higher mortality rate and developed to a more critical form of the disease compared with patients without DM.…”

Acute Metabolic Emergencies in Diabetes and COVID-19: a systematic review and meta-analysis of case reports

“…SARS-CoV-2 can trigger severe diabetic ketoacidosis at presentation in individuals with new-onset diabetes; however, there is no hard evidence that SARS-CoV-2 is etiologically linked with T1DM for the time being [85]. As DKA occurs as a result of insulin deficiency and increased counterregulatory responses, which favor the production of ketones, the unique interactions between SARS-CoV-2 and the RAAS might provide yet another mechanism in the pathophysiology of DKA firstly by direct entry of SARSCoV-2 into pancreatic islet cells that might worsen b-cell injury and secondly by downregulation of ACE2 after viral entry that can lead to unopposed angiotensin II and subsequent insulin secretion impedance [86]. It has been proposed that direct cytopathic effects of SARS-CoV-2 on pancreatic b-cell populations may contribute to this high prevalence of severe COVID-19-associated DKA in T2DM; ACE2 expression at both the mRNA and protein is increased substantially in human beta cells in response to inflammatory cytokines, presumably rendering these cells more susceptible to infection [90].…”

“…Another important aspect in DKA management is that of monitoring and correcting electrolyteabnormalities. As angiotensin II stimulates aldosterone secretion and increases renal potassium loss, this can potentiate the risk of hypokalemia, which might necessitate additional potassium supplementation in order to continue intravenous insulin to suppress ketogenesis[86][87][88][89].…”

Diabetic ketoacidosis during COVID-19 pandemic in a developing country

“…Accordingly, the virus can cause cellular destruction of the islets of Langerhans, which may explain the higher incidence of DKA [3] in patients with and without known diabetes. This damage can be expressed by an elevation of pancreatic enzyme levels in patients with COVID-19 [5] ; however, DKA itself can present with elevated pancreatic enzyme levels in 16–25% of cases [6] . Likewise, a state of insulin resistance triggered by COVID-19 has been described, which, together with pancreatic injury, contributes to an increased risk of hyperglycemic crisis in patients with diabetes [3] .…”