Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2021; 12(3): 215-237
Published online Mar 15, 2021. doi: 10.4239/wjd.v12.i3.215
Bidirectional link between diabetes mellitus and coronavirus disease 2019 leading to cardiovascular disease: A narrative review
Vijay Viswanathan, Anudeep Puvvula, Ankush D Jamthikar, Luca Saba, Amer M Johri, Vasilios Kotsis, Narendra N Khanna, Surinder K Dhanjil, Misha Majhail, Durga Prasanna Misra, Vikas Agarwal, George D Kitas, Aditya M Sharma, Raghu Kolluri, Subbaram Naidu, Jasjit S Suri
Vijay Viswanathan, M Viswanathan Hospital for Diabetes, M Viswanathan Diabetes Research Centre, Chennai 600013, India
Anudeep Puvvula, Annu’s Hospitals for Skin and Diabetes, Nellore 524101, Andhra Pradesh, India
Ankush D Jamthikar, Department of Electronics and Communications, Visvesvaraya National Institute of Technology, Nagpur 440010, Maharashtra, India
Luca Saba, Department of Radiology, University of Cagliari, Monserrato 09045, Cagliari, Italy
Amer M Johri, Department of Medicine, Division of Cardiology, Queen’s University, Kingston, ON K7L 3N6, Canada
Vasilios Kotsis, 3rd Department of Internal Medicine, Hypertension Center, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki 541-24, Greece
Narendra N Khanna, Department of Cardiology, Indraprastha APOLLO Hospitals, New Delhi 110020, India
Surinder K Dhanjil, Stroke Diagnosis and Monitoring Division, AtheroPoint™ LLC, CA 95661, United States
Misha Majhail, Jasjit S Suri, Stroke Diagnosis and Monitoring Division, AtheroPoint™, Roseville, CA 95661, United States
Durga Prasanna Misra, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
Vikas Agarwal, Departments of Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
George D Kitas, Academic Affairs, Dudley Group NHS Foundation Trust, Dudley DY1 2HQ, United Kingdom
George D Kitas, Arthritis Research UK Epidemiology Unit, Manchester University, Manchester M13 9PL, United Kingdom
Aditya M Sharma, Division of Cardiovascular Medicine, University of Virginia, Charlottesville, VA 22908, United States
Raghu Kolluri, OhioHealth Heart and Vascular, Ohio, OH 43082, United States
Subbaram Naidu, Electrical Engineering Department, University of Minnesota, Duluth, MN 55812, United States
Author contributions: Viswanathan V, Suri JS, Puvvala A, and Jamthikar A contributed conception and design; Dhanjil SK and Khanna NN contributed administrative support; Suri JS, Puvvala A, and Jamthikar A contributed manuscript writing; Johri AM, Kitas GD, Agarwal V, Misra DP, and Dhanjil SK contributed critical evaluation; Sharma A, Kolluri R, Dhanjil SK, Khanna NN, Jamthikar A, and Suri JS contributed vascular inputs; All authors have read and approved the final manuscript.
Conflict-of-interest statement: There is no conflict of interest among the authors. Dr. Jasjit Suri is affiliated with AtheroPoint™, focused in the area of stroke and cardiovascular imaging.
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:
Corresponding author: Jasjit S Suri, PhD, Professor, Stroke Diagnosis and Monitoring Division, AtheroPoint™, 208 Otter Glen Ct., Roseville, CA 95661, United States.
Received: November 6, 2020
Peer-review started: November 6, 2020
First decision: December 11, 2020
Revised: December 20, 2020
Accepted: February 11, 2021
Article in press: February 11, 2021
Published online: March 15, 2021

Coronavirus disease 2019 (COVID-19) is a global pandemic where several comorbidities have been shown to have a significant effect on mortality. Patients with diabetes mellitus (DM) have a higher mortality rate than non-DM patients if they get COVID-19. Recent studies have indicated that patients with a history of diabetes can increase the risk of severe acute respiratory syndrome coronavirus 2 infection. Additionally, patients without any history of diabetes can acquire new-onset DM when infected with COVID-19. Thus, there is a need to explore the bidirectional link between these two conditions, confirming the vicious loop between “DM/COVID-19”. This narrative review presents (1) the bidirectional association between the DM and COVID-19, (2) the manifestations of the DM/COVID-19 loop leading to cardiovascular disease, (3) an understanding of primary and secondary factors that influence mortality due to the DM/COVID-19 loop, (4) the role of vitamin-D in DM patients during COVID-19, and finally, (5) the monitoring tools for tracking atherosclerosis burden in DM patients during COVID-19 and “COVID-triggered DM” patients. We conclude that the bidirectional nature of DM/COVID-19 causes acceleration towards cardiovascular events. Due to this alarming condition, early monitoring of atherosclerotic burden is required in “Diabetes patients during COVID-19” or “new-onset Diabetes triggered by COVID-19 in Non-Diabetes patients”.

Keywords: COVID-19, Diabetes mellitus, Bidirectional association, Cardiovascular disease, Atherosclerotic burden, Imaging tools

Core Tip: This narrative review hypothesizes that there is a bidirectional link between diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). The first bidirectional link is from COVID-19 to DM due to pancreatic damage or renin-angiotensin-aldosterone system dysregulation or cytokine storm. This is caused by the endocytosis of severe acute respiratory syndrome coronavirus 2. The second bidirectional link is from DM to COVID-19 and is due to drug-induced or impaired immunity or raised furin levels in DM. The review furthers explores the five pathways leading to cardiovascular diseases.