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World J Diabetes. Sep 15, 2021; 12(9): 1550-1562
Published online Sep 15, 2021. doi: 10.4239/wjd.v12.i9.1550
Diabetes and COVID-19: Role of insulin resistance as a risk factor for COVID-19 severity
Charitha Gangadharan, Rupa Ahluwalia, Alben Sigamani
Charitha Gangadharan, Department of Clinical Research, Narayana Hrudayalaya Limited, Bangalore 560099, Karnataka, India
Rupa Ahluwalia, Consultant in Diabetes and Endocrinology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, United Kingdom
Alben Sigamani, Chief Scientific Officer, Numen Health, Bangalore 560095, Karnataka, India
Author contributions: Sigamani A conceived the idea; Gangadharan C wrote the first draft; Ahluwalia R contributed to the review, restructuring and modifications of the final draft; All the authors contributed for structuring and improvement of the final draft, and all approved the final draft.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alben Sigamani, MBBS, MD, MSc, Professor, Chief Scientific Officer, Numen Health, No. 19, 4th C Cross Koramangala Industrial, 5th Block, Area, Bengaluru 560095, Karnataka, India. dralbens@numenhealth.com
Received: February 19, 2021
Peer-review started: February 19, 2021
First decision: May 12, 2021
Revised: June 11, 2021
Accepted: July 30, 2021
Article in press: July 30, 2021
Published online: September 15, 2021
Abstract

Patients with diabetes are more susceptible to coronavirus disease 2019 (COVID-19), and as a consequence, develop more severe form of disease. This is partly due to a systemic inflammatory state and pro thrombotic milieu seen in metabolic syndrome. In this review, we attempt to explore the pathogenetic links between insulin resistance and COVID-19 disease severity. Insulin resistance is an underlying condition for metabolic syndromes, including type 2 diabetes, which impairs insulin signaling pathways affecting metabolic and cardiovascular homeostasis. A high concentration of circulating insulin shifts the balance to mitogen activated protein kinase (MAPK)-dependent signaling and causes endothelial cell damage. The phosphatidylinositol 3 kinase and MAPK dependent signaling pathways maintain a balance between nitric oxide-dependent vasodilator and endothelin-1 dependent vasoconstriction actions of insulin. Vascular smooth muscle cell dysfunction is responsible for inflammation and blood coagulation leading to microvascular and macrovascular complications in diabetes. Hyperactivity in renin-angiotensin system is implicated in development of islet oxidative stress and subsequent β-cell dysfunction, as it alters the islet blood flow. These deleterious effects of insulin resistance involving altered blood pressure, vascular dysfunction, and inflammation could be associated with increased severity in COVID-19 patients. We conclude that clinical and/or biochemical markers of insulin resistance should be included as prognostic markers in assessment of acute COVID-19 disease.

Keywords: Insulin resistance, Renin–angiotensin system, Blood flow measurements, Inflammation, Thrombosis, Severity of COVID-19

Core Tip: Diabetes has been associated with an increased risk of developing coronavirus disease 2019 (COVID-19) as well as more severe outcomes as a consequence. The pathogenetic link between insulin resistance and COIVD-19 disease severity is not fully understood. Establishing an association between insulin resistance and COVID-19 severity can help to develop targeted therapeutic interventions and potentially improve outcomes amongst the at-risk group.