While presence of diabetes has been frequently associated with Covid-19, new-onset hyperglycemia with or without diabetes and acute metabolic decompensation of pre-existing diabetes associated with Covid-19 have also garnered significant attention in the recent past. New-onset hyperglycemia is frequently seen in admitted patients with Covid-19, who had no history of dysglycemia or diabetes in the past and were currently not on corticosteroids. Emerging evidence suggests that Covid-19 may trigger the onset of diabetes in healthy people and also cause severe complications of pre-existing diabetes.Clinical observations provide support for the hypothesis of a potential diabetogenic effect of Covid-19. Besides precipitating new-onset diabetes, Covid-19 may also unmask previously undiagnosed diabetes through pleiotropic alterations in glucose metabolism. Patients with newly diagnosed diabetes, whether it is new-onset diabetes or previously undiagnosed diabetes, are likely to have high levels of inflammatory markers like interleukin-6 and indicators of multi-organ injury, thereby experiencing severe Covid-19.

Although the underlying mechanism remains unclear, previous research shows that angiotensin-converting enzyme 2, the protein that binds to severe acute respiratory syndrome coronavirus 2allowing the virus to enter human cells, is not only present in the lungs but also in organs and tissues involved in glucose metabolism such as the pancreas, the small intestine, the fat tissue, the liver and the kidney. It has been hypothesized that by entering these tissues, this virus may cause multiple and complex dysfunctions of glucose metabolism.

Thus, optimal glycemic control is of utmost importance inthis patient population to reduce the risk of threatening metabolic complications. With regard to this, favourable effects of metformin in patients with Covid-19 have been put forward. It can reduce inflammation, act as an antioxidant, and alter the composition of gut microbiota. These properties may help in combating the cytokine storm seen in patients with diabetes and Covid-19. Most notably, metformin use has been shown to cause a fourfold reduction in risk of in-hospital mortality. Moreover, optimal management of glucose levels and immune-modulating properties of this drug may help in improving patients’ outcomes.

It is noteworthy that Covid-19 patients with newly diagnosed diabetes are more likely to die than those with known diabetes. Clinicians need to be aware of these issues and should screen all Covid-19 patients with blood glucose and HbA1c at the time of admission, regardless of their prior diabetes history, and closely monitor their glycemic status. This will help in managinghyperglycemia early, as optimal glycemic control is shown to decrease disease severity and mortality in Covid-19 patients with diabetes. It may be speculated that metformin, the marketplace leader among glucose-lowering agents could favourably influence the clinical outcomes of patients with new-onset diabetes and also help in reducing the risk of severe Covid-19.

References

1. Hyperglycemia without diabetes and new-onset diabetes are both associated with poorer outcomes in COVID-19. Available at:https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30635-5/pdf. Accessed on 13 Oct 2020
2. COVID-19 may trigger new diabetes, experts warn. Available at: https://www.sciencedaily.com/releases/2020/06/200612172220.htm Accessed on: 13 Oct 2020.
3. Zimmet P, Alberti G, Bornstein S, et al. New-Onset Diabetes in Covid-19. N Engl J Med. 2020;383:789-790
4. Sathish T, Cao Y, Kapoor N. Newly diagnosed diabetes in COVID-19 patients [published online ahead of print, 2020 Aug 27]. Prim Care Diabetes. 2020;doi:10.1016/j.pcd.2020.08.014
5. Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. The Lancet Diabetes and Endocrinology. 2020;8(9):782-792.
6. Metformin as a Repurposed Host-Directed Therapy for Patients With Diabetes and COVID-19. Available at:  https://www.practiceupdate.com/content/metformin-as-a-repurposed-host-directed-therapy-for-patients-with-diabetes-and-covid-19/102193Accessed on 14 Oct 2020
7. COVID-19 and diabetes: Is metformin a friend or foe? Available at:https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30417-4/pdf. Accessed on 14 Oct 2020
8. Scheen AJ. Metformin and COVID-19: From cellular mechanisms to reduced mortality [published online ahead of print, 2020 Aug 1]. Diabetes Metab. 2020;S1262-3636(20)30098-7.