COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

Hayder M Al-Kuraishy; Ali I Al-Gareeb; M Alblihed; Susana G Guerreiro; Natália Cruz-Martins; Gaber El-Saber Batiha

doi:10.3389/fcvm.2021.644095

COVID-19 in Relation to Hyperglycemia and Diabetes Mellitus

Front Cardiovasc Med. 2021 May 20:8:644095. doi: 10.3389/fcvm.2021.644095. eCollection 2021.

Authors

Hayder M Al-Kuraishy¹, Ali I Al-Gareeb¹, M Alblihed², Susana G Guerreiro^{3

4

5}, Natália Cruz-Martins^{3

5

6}, Gaber El-Saber Batiha⁷

Affiliations

¹ Department of Clinical Pharmacology and Therapeutic Medicine, College of Medicine, ALmustansiriyiah University, Baghdad, Iraq.
² Department of Microbiology, College of Medicine, Taif University, Taif, Saudi Arabia.
³ Faculty of Medicine, University of Porto, Porto, Portugal.
⁴ Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
⁵ Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal.
⁶ Laboratory of Neuropsychophysiology, Faculty of Psychology and Education Sciences, University of Porto, Porto, Portugal.
⁷ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.

Abstract

Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic β-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern.

Keywords: COVID-19; SARS-CoV-2; cardiometabolic disturbances; diabetes mellitus; hyperglycemia.

Publication types

Review