An international team of scientists is investigating the curious bi-directional relationship between COVID-19 and diabetes. The researchers suggest SARS-CoV-2 infection may actively be triggering the onset of diabetes and a global registry has been set up to track this growing phenomenon.
Early on in the pandemic it quickly became clear people with pre-existing medical conditions were hit harder with COVID-19. Those with diabetes or heart disease were known to suffer more severely from COVID-19 but some clinicians were beginning to see cases with the direction of the relationship switched around. Subjects who were healthy before COVID-19 were subsequently developing diabetic symptoms during, or following, their acute coronavirus infection.
Early in 2020, Francesco Rubino, a metabolic and bariatric surgeon from King’s College London, began to notice a growing number of anecdotal reports of new-onset diabetes diagnoses following COVID-19 infection. By the middle of the year Rubino had joined forces with colleagues around the world to form the CoviDiab project.
The project is an online global registry calling for doctors around the world to contribute reports of cases of new-onset diabetes linked to COVID-19. A New England Journal of Medicine correspondence from Rubino in August last year, and co-signed by 16 other researchers, announced the registry suggesting there are plausible mechanisms by which COVID-19 could trigger the onset of diabetes.
“The goal of the registry is to establish the extent and phenotype of new-onset diabetes that is defined by hyperglycemia, confirmed Covid-19, a negative history of diabetes, and a history of a normal glycated hemoglobin level,” the researchers explained in their correspondence. “The registry, which will be expanded to include patients with preexisting diabetes who present with severe acute metabolic disturbance, may also be used to investigate the epidemiologic features and pathogenesis of Covid-19–related diabetes and to gain clues regarding appropriate care for patients during and after the course of Covid-19.”
Since the CoviDiab registry was launched a small but growing body of evidence has been building suggesting some kind of relationship between new-onset diabetes and COVID-19. A systematic review and meta-analysis published in late 2020 pooled data from eight studies encompassing 3,711 COVID-19 patients and detected 492 newly diagnosed cases of diabetes.
A more recent long-COVID study tracked nearly 50,000 patients post-discharge for up to five months. The paper, not yet peer-reviewed or published, found 4.9 percent of hospitalized patients were subsequently diagnosed with diabetes in the months following discharge.
“Over the last few months, we’ve seen more cases of patients that had either developed diabetes during the Covid-19 experience, or shortly after that,” Rubino recently told The Guardian. “We are now starting to think the link is probably true – there is an ability of the virus to cause a malfunctioning of sugar metabolism.”
The association between newly diagnosed diabetes and COVID-19 may certainly be growing but big questions regarding causation remain. There are certainly plausible mechanisms by which SARS-CoV-2 could, at the very least, speed up the progression of diabetes in individuals already prone to the disease.
“SARS-Cov-2, the virus responsible for COVID-19, binds to ACE-2 receptors, which are expressed in several key metabolic organs and tissues including the pancreatic β-cells, adipose tissue, small intestine, liver, and kidney,” the CoviDiab website says. “Thus, it is plausible that SARS-Cov-2 could cause multiple co-existing alterations of glucose metabolism that can complicate the pathophysiology of pre-existing diabetes or lead to new mechanisms of disease.”
But, there are several other scenarios that could also potentially explain this growing association. Severe cases of COVID-19, much like many cases of acute illness, can trigger inflammatory processes in the body that lead to hyperglycemia. Plus, many anti-viral and steroid treatments used to fight COVID-19 can raise blood sugar and cause symptoms of diabetes.
Another hypothesis is these new cases of diabetes were actually not new at all but rather they were patients in undiagnosed states of prediabetes. Striking research from the Centers of Disease Control and Prevention (CDC) suggests over seven million people in the US currently suffer from undiagnosed diabetes, and tens of millions more may be in prediabetic states.
So is COVID-19 explicitly causing a new kind of diabetes? Is it speeding up development of the disease in those already prone? Or, is the nature of the pandemic simply leading to doctors catching more cases of undiagnosed diabetes in the general population?
These are exactly the questions the CoviDiab project hopes to answer. The researchers plan to engage in a preliminary analysis of their data once the registry reaches 200 case reports. Rubino suggests they are very close to that target.
If COVID-19 does increase one’s risk of subsequently developing diabetes it will take time and careful surveillance to identify. Projects like CoviDiab will be vital in understanding the long-term health impacts of this pandemic.
