Document Type : Review Article


1 Department of Clinical Pharmacy, College of Pharmacy, University of Basrah, Basra, Iraq.

2 Department of pharmacology, College of Pharmacy, University of Basrah, Basra, Iraq.


Background: COVID-19 pandemic associates with many acute and long-term effects. Hyperglycemia and diabetes are among the common comorbidities that negatively affect the outcome of COVID-19 patients. Many studies report an increase in the incidence of new-onset diabetes and diabetic ketoacidosis during the pandemic of COVID-19. 
Aim of the Study: This review article aimed to study the bidirectional relationship between diabetes and COVID-19 and understand the possible underlying mechanisms predisposed to diabetes in patients with COVID-19. 
Methods: The present work performs an online literature search on databases from PubMed, Google Scholar, Scopus, ResearchGate, and Web of Science. The search includes publications on SARS-CoV-2 or COVID-19, hyperglycemia, diabetes, and diabetic ketoacidosis.  
Results: There is a slight increase in the incidence of hyperglycemia and new-onset diabetes during or post COVID-19 infections. Among the proposed mechanisms of that increase are the direct and indirect effects of SARS-CoV-2 on Beta cells of the pancreas. These effects arise from viral-mediated inflammatory and immunological effects on Beta cells. Stress hyperglycemia, corticosteroid administration, obesity, and preexisting diabetes are important aggravating factors for developing diabetes in COVID-19 patients. 
Conclusion: The long-term follow-up is mandatory to determine the outcome of patients, who develop new-onset diabetes after COVID-19 infection.


1- Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-3.   
2- WHO Director-General's opening remarks at the media briefing on COVID-19—Mar 11 2020.
3- World Health Organization. Coronavirus disease (COVID-2019) situation reports. 2020.
4- Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, Hou C, Wang H, Liu J, Yang D, Xu Y. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Critical Care. 2020 Dec;24(1):1-0.
5- Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation. 2021 Feb;44(1):13-34.
6- Parohan M, Yaghoubi S, Seraji A, Javanbakht MH, Sarraf P, Djalali M. Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. The Aging Male. 2020 Dec 4;23(5):1416-24.
7-Keerthi BY, Sushmita G, Khan EA, Thomas V, Cheryala V, Shah C, Kumar GR, Haritha V. New onset diabetes mellitus in post-COVID-19 patients. Journal of Family Medicine and Primary Care. 2022 Oct 1;11(10):5961-8.
8-de Sá-Ferreira CO, da Costa CH, Guimarães JC, Sampaio NS, Silva LD, de Mascarenhas LP, Rodrigues NG, Dos Santos TL, Campos S, Young EC. Diabetic ketoacidosis and COVID-19: what have we learned so far?. American Journal of Physiology-Endocrinology and Metabolism. 2022 Jan 1;322(1):E44-53.
9-Egi M, Furushima N, Makino S, Mizobuchi S. Glycemic control in acute illness. Korean Journal of Anesthesiology. 2017 Dec;70(6):591.
10- Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility. Cell. 2015 Feb 26;160(5):816-27.
11-Šestan M, Marinović S, Kavazović I, Cekinović Đ, Wueest S, Wensveen TT, Brizić I, Jonjić S, Konrad D, Wensveen FM, Polić B. Virus-induced interferon-γ causes insulin resistance in skeletal muscle and derails glycemic control in obesity. Immunity. 2018 Jul 17;49(1):164-77.
12-Zhang Y, Li H, Zhang J, Cao Y, Zhao X, Yu N, et al. The clinical characteristics and outcomes of diabetes mellitus and secondary hyperglycaemia patients with coronavirus disease 2019: a single-center, retrospective, observational study in Wuhan. Diabetes Obes Metab. (2020) 22:1443–54. 
13- Chen J, Wu C, Wang X, Yu J, Sun Z. The impact of COVID-19 on blood glucose: a systematic review and meta-analysis. Frontiers in endocrinology. 2020 Oct 5;11:574541.
14- Smith SM, Boppana A, Traupman JA, Unson E, Maddock DA, Chao K, Dobesh DP, Brufsky A, Connor RI. Impaired glucose metabolism in patients with diabetes, prediabetes, and obesity is associated with severe COVID‐19. Journal of medical virology. 2021 Jan;93(1):409-15.
15-Bradley SA, Banach M, Alvarado N, Smokovski I, Bhaskar SM. Prevalence and impact of diabetes in hospitalized COVID‐19 patients: A systematic review and meta‐analysis. Journal of diabetes. 2022 Feb;14(2):144-57.
16-Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H. Association of blood glucose control and outcomes in patients with COVID-19 and preexisting type 2 diabetes. Cell metabolism. 2020 Jun 2;31(6):1068-77. 
17-Zhu Z, Mao Y, Chen G. Predictive value of HbA1c for in-hospital adverse prognosis in COVID-19: A systematic review and meta-analysis. Primary Care Diabetes. 2021 Dec 1;15(6):910-7.
18-Vlad A, Serban V, Timar R, Sima A, Botea V, Albai O, Timar B, Vlad M. Increased incidence of type 1 diabetes during the COVID-19 pandemic in Romanian children. Medicina. 2021 Sep 16;57(9):973.
19-Unsworth R, Wallace S, Oliver NS, Yeung S, Kshirsagar A, Naidu H, Kwong RM, Kumar P, Logan KM. New-onset type 1 diabetes in children during COVID-19: multicenter regional findings in the UK. Diabetes Care. 2020 Nov 1;43(11):e170-1.
20-Salmi H, Heinonen S, Hästbacka J, Lääperi M, Rautiainen P, Miettinen PJ, Vapalahti O, Hepojoki J, Knip M. New-onset type 1 diabetes in Finnish children during the COVID-19 pandemic. Archives of disease in childhood. 2022 Feb 1;107(2):180-5.
21-Burekovic A, Asimi ZV, Divanovic A, Halilovic D. Diabetes-a Consequence of COVID-19 Infection. Materia Socio-Medica. 2022 Mar;34(1):4.
22-Guo Y, Bian J, Chen A, Wang F, Posgai AL, Schatz DA, Shenkman EA, Atkinson MA. Incidence Trends of New-Onset Diabetes in Children and Adolescents Before and During the COVID-19 Pandemic: Findings From Florida. Diabetes. 2022 Dec;71(12):2702-6.
23-Ramos-Yataco A, Davila EA, Meza K, Harbuz-Miller I. New-Onset and Persistent Insulin-Dependent Diabetes in Patients With COVID-19: A Peruvian Experience. Cureus. 2022 Jul 26;14(7).
24- Rathmann W, Kuss O, Kostev K. Incidence of newly diagnosed diabetes after Covid-19. Diabetologia. 2022 Jun;65(6):949-54.
25- Khreefa Z, Barbier MT, Koksal AR, Love G, Del Valle L. Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas. Cells. 2023 Jan 9;12(2):262.
26-Liu F, Long X, Zhang B, Zhang W, Chen X, Zhang Z. ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection. Clinical Gastroenterology and Hepatology. 2020 Aug 1;18(9):2128-30.
27- Mine K, Nagafuchi S, Mori H, Takahashi H, Anzai K. SARS-CoV-2 Infection and Pancreatic β Cell Failure. Biology (Basel). 2021 Dec 24;11(1):22. 
28-Tang X, Uhl S, Zhang T, Xue D, Li B, Vandana JJ, Acklin JA, Bonnycastle LL, Narisu N, Erdos MR, Bram Y. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell metabolism. 2021 Aug 3;33(8):1577-91.
29- Tang X, Uhl S, Zhang T, et al. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab. 2021 Aug 3;33(8):1577-1591.e7. 
30- Steenblock C, Richter S, Berger I, et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat. Commun2021;12:3534.
31- Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, Jiang S, Demeter J, Bevacqua RJ, Chang CA, Whitener RL. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell metabolism. 2021 Aug 3;33(8):1565-76.
32- Qadir MMF, Bhondeley M, Beatty W, et al. SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes. JCI Insight. 2021 Aug 23;6(16):e151551. 
33- Kusmartseva I, Wu W, Syed F, Van Der Heide V, Jorgensen M, Joseph P, Tang X, Candelario-Jalil E, Yang C, Nick H, Harbert JL. Expression of SARS-CoV-2 entry factors in the pancreas of normal organ donors and individuals with COVID-19. Cell metabolism. 2020 Dec 1;32(6):1041-51.
34- Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet. 2009), 373:1798–807.
35- Marik PE, Bellomo R. Stress hyperglycemia: an essential survival response. Crit Care. 2013,17:305. 
36- Van Cromphaut SJ. Hyperglycaemia as part of the stress response: the underlying mechanisms. Best Practice & Research Clinical Anaesthesiology. 2009 Dec 1;23(4):375-86.
37- Ilias I, Zabuliene L. Hyperglycemia and the novel Covid-19 infection: Possible pathophysiologic mechanisms. Medical Hypotheses. 2020 Jun;139:109699.
38- Hayden MR. An immediate and long-term complication of COVID-19 may be type 2 diabetes mellitus: the central role of β-cell dysfunction, apoptosis and exploration of possible mechanisms. Cells. 2020 Nov 13;9(11):2475.
39- Metwally AA, Mehta P, Johnson BS, Nagarjuna A, Snyder MP. COVID-19–induced new-onset diabetes: trends and technologies. Diabetes. 2021 Dec;70(12):2733-44.
40- Shrestha DB, Budhathoki P, Raut S, Adhikari S, Ghimire P, Thapaliya S, Rabaan AA, Karki BJ. New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis. World Journal of Virology. 2021 Sep 9;10(5):275.
41- Smith SM, Boppana A, Traupman JA, Unson E, Maddock DA, Chao K, Dobesh DP, Brufsky A, Connor RI. Impaired glucose metabolism in patients with diabetes, prediabetes, and obesity is associated with severe COVID‐19. Journal of medical virology. 2021 Jan;93(1):409-15.
42- Simonnet A, Chetboun M, Poissy J, et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) requiring invasive mechanical ventilation. Obesity. 2020 Jul;28(7):1195-9
43- Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, et al. Severe obesity is associated with higher in-hospital mortality in a cohort of patients with COVID-19 in the Bronx. New York. Metabolism. 2020; 108:154262.
44-Zatterale F, Longo M, Naderi J, Raciti GA, Desiderio A, Miele C, Beguinot F. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020 Jan 29; 10:1607. 
 45- Mohammad S, Aziz R, Al Mahri S, Malik SS, Haji E, Khan AH, Khatlani TS, Bouchama A. Obesity and COVID-19: What makes obese host so vulnerable? Immunity & Ageing. 2021 Dec; 18:1-0.
46-Thakur M, Datusalia AK, Kumar A. Use of steroids in COVID-19 patients: A meta-analysis. Eur J Pharmacol. 2022 Jan 5; 914:174579. 
47- Sari DA, Samodra G, Kusuma IY. Molecular mechanism of glucocorticoid-induced hyperglycemia. Pharmacy Reports. 2021 Aug 31;1(1):1-. 
48-Liu X, Zhu X, Miao Q, Ye H, Zhang Z, Li Y: Hyperglycemia Induced by Glucocorticoids in Nondiabetic Patients: A Meta-Analysis. Ann Nutr Metab 2014;65:324-332. 
49-Rana MA, Siddiqui MH, Raza SI, Tehreem K, Ullah MF, Mahmood MJ, Qayyum MA, Hafeez MM. Incidence of steroid-induced diabetes in COVID-19 patients. Pakistan Journal of Medical and Health Sciences. 2021;15(10):2595-6.