Diabetes as a risk-factor for severe COVID-19

Diabetes as a risk-factor for severe COVID-19

Diabetic population is often vulnerable to severe outcomes in chronic and acute infections. Due to such implication, the relationship between diabetes and COVID-19 (SARS-CoV-2) has been eagerly pursued by the scientific community throughout the past 2 years of the pandemic. Through many analysis studies, diabetes has been found to be a significant risk factor associated with worse prognosis of COVID-19 infection.

What might be some possible reasons for severe COVID-19 outcomes in patients with diabetes?

Several studies report diabetes mellitus to be an independent predictor of higher ICU admissions and/or mortality rates in COVID-19 patients. The primary reason seems to be weakened immunity response due to chronic metabolic dysfunction of diabetes. Specifically, prolonged hyperglycemia and macrovascular complications were among the two conditions suggested to be distressing and dysregulating the immune system. An elevated level of Interleukin-6 (IL-6), a common marker of diabetes mellitus, along with higher levels of other inflammation-related biomarkers, collectively identified as an “inflammatory storm,” suggest ongoing damage to proteins, lipids, DNA, deteriorating the body’s structure and function.

Abnormalities in lung physiology and function due to oxidative stress from prolonged hyperglycemia may present as another reason. A study found that dyspnea, or difficulty breathing, at the time of hospital admission, was a positive predictor of increased mortality rate and negative predictor of discharge within 28 days of admission.

Can COVID-19 cause diabetes?

How does COVID-19 affect diabetes?

Impaired glucose metabolism, such as unusual hepatic glucose production and insulin resistance, may result in response to inflammation of COVID-19 infection, resulting in hyperglycemia

So far, it has not been proven that COVID-19 can cause diabetes. However, there are many ways COVID-19 seems to impact diabetes. Impaired glucose metabolism, such as unusual hepatic glucose production and insulin resistance, may result in response to inflammation of COVID-19 infection, resulting in hyperglycemia. An article published by Wu et al. (2020) found that there was need for higher administration of insulin required to control blood glucose level for COVID-19 patients.

Another study from 2010 showed that certain SARS-CoV patients without pre-existing diabetes mellitus newly developed hyperglycemia after infection. One proposed explanation is that the viral infection has done a long-term damage to pancreatic beta cells through an entry-receptor for SARS-CoV, namely ACE2. ACE2 is reported to be predominantly expressed in various tissues, such as the vasculature and pancreas, including pancreatic islets. ACE2 is also considered an entry-receptor for SARS-CoV-2 (COVID-19), likely producing similar effects. However, whether ACE2 is truly expressed in pancreatic islets, damaging the beta-cells, is still debated, warranting further studies.

Increased ketoacidosis prevalence among COVID-19 patients with pre-existing type 2 diabetes mellitus has been reported. Many factors may play a role in this phenomenon, including damage to the pancreatic beta-cells via inflammatory storm, dehydration due to fever and lack of fluid intake, and possibly concurrent kidney damage or respiratory distress.

A prothrombotic state, increasing the likelihood of a blood clot, may be induced by SARS-CoV-2 infection of vascular endothelial cells via ACE2 receptors. The inflammatory response to the viral infection also has shown increased release of coagulation factors in the blood vessels, as well as dysregulation and apoptosis of endothelial cells, requiring attentive management of cardiovascular complications in diabetic patients.

How do diabetes medications affect the prognosis of COVID-19?

Metformin has the preventative potential to reduce the risk of COVID-19 mortality in patients with diabetes when taken before the diagnosis of COVID-19

A CORONADO study published in February 2021 revealed findings that a routine metformin and dipeptidyl peptidase 4 inhibitors (DPP-4) therapies were each positive predictors of discharge within 28 days for COVID-19 patients admitted with diabetes.

A study by Crouse et al. (2021) stated that metformin has the preventative potential to reduce the risk of COVID-19 mortality in patients with diabetes when taken before the diagnosis of COVID-19 (11% mortality rate vs 24% in patients not on metformin prior to COVID-19 diagnosis). However, another study published around a similar time, concluded that while metformin was safe to use in mild to moderate COVID-19 patients, it should be used with caution on critically ill patients with severe respiratory problems.

DPP-4, in addition to ACE2, has been indicated as the other potential entry receptor for binding of SARS-CoV2. This may provide a possible explanation for better COVID-19 prognosis with the use of DPP-4 inhibitors.

The use of insulin shows mixed result in its safety or efficacy of COVID-19 mortality rate. While some studies have no findings in the dangers of insulin used for treatment of people with COVID-19 and diabetes, others have found contrasting results. The same CORONADO study published in Feb 2021 also recognized insulin as a negative predictor of discharge and a positive predictor of death. A retrospective study done in Wuhan, China revealed that 27.2% of patients with COVID-19 and diabetes experienced deaths with insulin treatment compared to 3% of those without. However, these studies should be interpreted cautiously since such findings may not necessarily mean that insulin itself has a harmful effect. Rather, it could simply indicate a parallel relationship between difficulty in glycemic control (needing insulin therapies) and worse outcomes.

Since COVID-19 shows trends of making it more difficult to control blood glucose levels and promoting insulin resistance through various mechanisms, frequent monitoring of blood glucose levels seems to become even more critical for all diabetic patients. New information and findings are continually being updated. However, there are still many incomplete speculations and conflicting results. All medical advice concerning COVID-19 and diabetes should be discussed with medical professionals and providers.


- Lim, S., Bae, J.H., Kwon, HS. et al.COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol 17, 11–30 (2021). https://doi.org/10.1038/s41574-020-00435-4
- Zhou, Y, Chi, J, Lv, W, Wang, Y. Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19). Diabetes Metab Res Rev. 2021; 37:e3377. https://doi.org/10.1002/dmrr.3377
- Accili, D. Can COVID-19 cause diabetes?. Nat Metab3, 123–125 (2021). https://doi.org/10.1038/s42255-020-00339-7
- Yang, J.K., Lin, S.S., Ji, X.J., Guo, L.M. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol, 47, 193-9 (2010). doi: 10.1007/s00592-009-0109-4. Epub 2009 Mar 31. PMID: 19333547; PMCID: PMC7088164.
- Wargny, M., Potier, L., Gourdy, P. et al.Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study. Diabetologia 64, 778–794 (2021). https://doi.org/10.1007/s00125-020-05351-w
- Corona, G., Pizzocaro, A., Vena, W. et al.Diabetes is most important cause for mortality in COVID-19 hospitalized patients: Systematic review and meta-analysis. Rev Endocr Metab Disord 22, 275–296 (2021). https://doi.org/10.1007/s11154-021-09630-8
- Crouse, A.B., Grimes, T., Li, P., Might, M. et al. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. Front Endocrinol 11, 600439 (2021). https://doi.org/10.3389/fendo.2020.600439
- Yu, B., Li, C., Sun, Y., Wang, D.W. Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes. Cell Metabolism 33, 2-4 (2021). https://doi.org/10.1016/j.cmet.2020.11.014
- Wu, L., Girgis, C. M. & Cheung, N. W. COVID-19 and diabetes: insulin requirements parallel illness severity in critically unwell patients. Endocrinol.93, 390–393 (2020).



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