There is a bidirectional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with an increased risk of severe Covid-19. On the other hand, new-onset diabetes and severe metabolic complications of preexisting diabetes, including diabetic ketoacidosis and hyperosmolarity for which exceptionally high doses of insulin are warranted, have been observed in patients with Covid-19.^1-3 These manifestations of diabetes pose challenges in clinical management and suggest a complex pathophysiology of Covid-19–related diabetes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19, binds to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys.⁴ Thus, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of preexisting diabetes or lead to new mechanisms of disease.

There are also several precedents for a viral cause of ketosis-prone diabetes, including other coronaviruses that bind to ACE2 receptors.⁵ Greater incidences of fasting glycemia and acute-onset diabetes have been reported among patients with SARS coronavirus 1 pneumonia than among those with non-SARS pneumonia.⁵

In the aggregate, these observations provide support for the hypothesis of a potential diabetogenic effect of Covid-19, beyond the well-recognized stress response associated with severe illness. However, whether the alterations of glucose metabolism that occur with a sudden onset in severe Covid-19 persist or remit when the infection resolves is unclear. How frequent is the phenomenon of new-onset diabetes, and is it classic type 1 or type 2 diabetes or a new type of diabetes? Do these patients remain at higher risk for diabetes or diabetic ketoacidosis? In patients with preexisting diabetes, does Covid-19 change the underlying pathophysiology and the natural history of the disease? Answering these questions in order to inform the immediate clinical care, follow-up, and monitoring of affected patients is a priority….”