When SARS-CoV-2 first hit the scene in 2019, it quickly became clear that the disease had an … interesting interaction with diabetes. First of all, people with diabetes were getting sicker, needing hospitalization more often, and were more likely to die from the virus than people without diabetes – something that scientists are only now starting to understand. However, even more curious was the effect in the opposite direction: the fact, noticed as far back as July 2020, that the SARS-CoV-2 virus seemed to sometimes trigger diabetes in people who previously had no history of the condition.
There were various theories put forward to explain this. Perhaps it was fatigue and muscle loss from severe COVID-19 infection that triggered the onset of diabetes, or maybe it was too much inflammation. Some scientists suspected the ACE-2 protein was involved, and some blamed an overenthusiastic immune response. Now, a new potential mechanism has been put forward: COVID-19 may be able to infiltrate the cells in the pancreas responsible for insulin production, changing their function.
“We call it transdifferentiation,” Professor Shuibing Chen, who presented the results at the annual meeting of the European Association for the Study of Diabetes on Wednesday, told The Guardian. “They are basically changing their cellular fate, so instead of being hardcore beta cells which secrete a lot of insulin, they start to mix different hormones. It could provide further insight into the pathological mechanisms of COVID-19.”
Chen is part of a team that has been conducting cutting-edge research on the potential effects of COVID-19 throughout the body. Rather than simply recording complications as they turn up in medical literature, they instead studied organoids – lab-grown cell clusters that mimic the function of various organs – to see which were vulnerable to the SARS-CoV-2 virus.
Although we think of COVID-19 as primarily a respiratory disease, it wasn’t just the lung organoids that turned out to be susceptible. The team’s results suggested that the colon, heart, and liver, plus dopamine-producing brain cells and pancreatic organoids, could also be infected by the SARS-CoV-2 virus. Crucially, so could the endocrine cells in the pancreas that are known as alpha (α) and beta (β) cells.
"Whereas β-cells produce insulin to decrease blood-sugar levels, α-cells produce the hormone glucagon, which increases blood sugar," explains a June 2020 Nature report. The beta cells in particular express high levels of the ACE-2 proteins that are targeted by COVID-19 – and once infected, Chen explained, they start to produce less insulin. To compound the issue, these cells can also be killed off by the body's immune response to COVID-19, per a paper by Chen's team that was published last year in the journal Cell Stem Cell, hitting the body with a double whammy of endocrine disruption.
The good news is that these changes may not be permanent, Chen added.
“We know that some patients who had very unstable blood glucose levels when they were in the intensive care unit and recovered from COVID-19, some of them also recovered [glucose control],” she told The Guardian. She said this suggests that "that not all patients will be permanent.”
While the research offers an intriguing insight into how COVID-19 may induce diabetes in previously healthy patients, other researchers caution that it’s not the whole story.
“At least clinically, one of the things we’re seeing is that in some cases, patients who already had type 1 diabetes have started to express severe insulin resistance, which is a typical feature of type 2 diabetes,” Francesco Rubino, chair of metabolic surgery at King’s College London, told The Guardian. “This may imply a problem with how cells elsewhere in the body are responding to insulin after COVID-19 infection.”