There is emerging evidence that the relationship between COVID-19 and diabetes is bi-directional. Recent observations suggest that COVID-19 symptoms are not only exacerbated by diabetes but that SARS-CoV-2 (the virus causing COVID-19) also triggers the development of diabetes in non-diabetic COVID-19 patients.
Centers for Disease Control and Prevention (CDC) has reported that the risk of fatality from COVID-19 is up to 50% greater in diabetics. Although this mortality rate can be attributed, at least in part, to the impaired innate immunity of diabetics and the prevalence of cardiovascular disease in older diabetics, a more immediate cause has been suggested – COVID-19 induced diabetic ketoacidosis (DKA). DKA is the life-threatening acidification of the blood by ketones, acids produced when the body burns fat. This acidification is most common in diabetics, but is also reported in COVID-19 patients with no history of diabetes, suggesting SARS-CoV-2 induced diabetes.
This raises questions around the molecular means by which COVID-19 induces ketoacidosis. Angiotensin-converting enzyme 2 (ACE2) is the proposed molecular link between COVID-19 and diabetes; it is highly expressed in both the lungs and the pancreas. In the lungs, ACE2 serves as the entry point for SARS-CoV-2 by binding the virus’ spike glycoprotein, which is responsible for host-to-host transmission. ACE2 expression in the pancreas may allow spreading of the infection to pancreatic β-cells, which are responsible for insulin production. Viral infection therefore impedes insulin production, which in turn impairs glucose metabolism, causing diabetes and ketoacidosis.
The phenomenon of virally induced new-onset diabetes would not be unique to SARS-CoV-2. Previous studies have supported this hypothesis in enterovirus, rotavirus, cytomegalovirus – and most notably other coronaviruses. In 2010, SARS-CoV, the coronavirus responsible for severe acute respiratory syndrome (SARS), was hypothesised to cause diabetes. In this study, 50% of SARS patients displayed new-onset diabetes, 10% of which still had diabetes 3 years later.
The potential synergism of the two pandemics is of great concern.
These observations raise many questions about the potential diabetogenic effect of COVID-19, most significantly the nature of the new-onset diabetes and whether it will resolve following the infection or persist indefinitely. In hopes of gathering the data required to answer these questions and address this medical concern, a global registry, CoviDiab, was launched to collect data on new cases of diabetes in COVID-19 patients.
Despite the excitement surrounding the CoviDiab registry, researchers and medics alike have urged that we resist the temptation to treat these observations as evidence of COVID-19 induced diabetes. British based researchers Abd Tahrani from the University of Birmingham, and Naveed Sattar from the University of Glasgow, were quoted in Nature expressing their reservations, a sentiment shared by a piece published in Hospital Healthcare Europe.
Despite the reservations over the limited evidence, the new-onset of diabetes in COVID-19 is an alarming prospect as both pandemics continue to grow, with this week marking the 10 millionth positive case of COVID-19, and the prevalence of diabetes nearing 10% globally. The potential synergism of the two pandemics – seen in the exacerbation of COVID-19 in diabetics, and the potential new-onset of diabetes in COVID-19 patients – is of great concern.
Written by Seán Dunphy and edited by Ailie McWhinnie.
Seán‘s thoughts… Although there is limited evidence to support the hypothesis of SARS-CoV-2 induced diabetes, the gravity of the two pandemics and the mechanistic links between COVID-19 and diabetes warrant careful monitoring of the emerging data. The CoviDiab registry will likely function as a vital tool for measuring the relevance of these early observations, and could provide a valuable platform for research into SARS-CoV-2 induced diabetes.
Virally induced metabolic disorders are largely under-reported when compared to the numbers of patients affected. For example, chronic fatigue syndrome, which reportedly follows viral infection, affects nearly 0.5% of the UK population. Data linking metabolic disorders to viral infections are largely anecdotal, and timescales of infection and symptom development are often difficult to determine. The CoviDiab registry is unique in the opportunity it presents to record both the positive testing for the suspect virus, and the data needed to establish a strong correlation, and concrete timeline, of the emergence of symptoms of metabolic disorders.
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