COVID-19 is linked to new diabetes cases—but long-term problems could be more severe

Almost daily microbiologist Peter Jackson receives emails from people who recovered from COVID-19 only to discover that their health troubles have just begun.

Recently, a mother of two in her 30s wrote to the Stanford University professor to say that she now takes a slew of diabetes medications every day—even though she hadn’t been at risk for the disease before her coronavirus infection.

Experts have known since the beginning of the pandemic that having diabetes—a condition when the body doesn’t make enough insulin or use it well enough to counteract a rise in blood sugar—is a risk factor for more severe COVID-19 infections. But they have also long suspected that the inverse might be true as well. In May, Jackson published a study in the journal Cell Metabolism showing that SARS-CoV-2 infects cells in the pancreas that produce insulin and may even target and destroy them—suggesting that the virus may also cause diabetes. (Why scientists began investigating the link between COVID-19 and diabetes.)

“This is a real thing,” Jackson says of the complaints from newly diabetic people that have flooded his inbox. Although some experts argue that the condition is rare, Jackson says the data suggests that in 2020 as many as 100,000 people were diagnosed with an unexpected case of diabetes.

He is one of many scientists who worry there could be a new wave of diabetes patients who will have to monitor their blood sugar levels for the rest of their lives. But he and his colleagues are also concerned that the virus may be harming the pancreas in ways that may not be visible now but could one day have troubling implications for the organ itself and for the rest of the digestive system.

“This could be a pandemic in a pandemic,” says Paolo Fiorina, a professor of endocrinology at the University of Milan and lecturer at Harvard Medical School, who has also spearheaded investigations into the connection between COVID-19 and diabetes.

Scientists are still hashing out how serious a threat COVID-19 poses to the pancreas in the long term—and whether those who do develop diabetes are really stuck with it forever. Although it will take large studies and potentially many years to answer those questions, researchers are already on the case.

How COVID damages the pancreas

First, a refresher on the pancreas—an organ that plays a key role in the digestive system. Located behind the stomach, the widest part of the pancreas is connected to the small intestine, close to where the stomach empties partially digested food. There, the pancreas secretes a variety of juices to the mix to further break it down.

Most of that food is broken down into sugar that is released into the bloodstream. The pancreas is responsible for regulating those blood sugar levels by producing hormones: insulin, which lowers blood sugar, and glucagon, which raises it. But if this glucose balance isn’t carefully regulated, prolonged high blood glucose can cause organs to malfunction and permanently damage the retina, kidneys, nerves, heart, and blood vessels.

In Italy, a COVID-19 epicenter in the earliest days of the pandemic, it became clear that the blood sugar levels of people who were hospitalized with COVID-19 were out of whack. Fiorina became interested in investigating these effects in April 2020. At the time, he was the chief of endocrinology at a hospital in Milan, which saw upwards of 20,000 new cases of COVID-19 on a daily basis—and held one funeral every hour.

One day, a pathologist remarked to Fiorina how strange it was that so many of the patients who had died were hyperglycemic, meaning that their blood sugar was too high—a sign that the pancreas wasn’t doing its job. “I know that people with diabetes are more prone to dying,” Fiorina recalls telling the pathologist at the time. “But there might be something else.”

Fiorina decided to investigate. In May 2021, he published a study of 551 patients with no prior history of diabetes showing that 46 percent were newly hyperglycemic. COVID-19 had completely disrupted the hormone profile of these patients—although their levels had been normal before their infection, now their glucose was dangerously high as their body had become less efficient at using insulin.

Around the same time, autopsies of people who died from COVID-19 also showed that the virus had infected the pancreas—which researchers confirmed in a set of studies published in the journal Cell Metabolism. Jackson, who was among those researchers, found that SARS-CoV-2 infects and kill the beta cells that produce insulin. It’s thought that these cells are not easily replenished—and losing them makes you more susceptible to diabetes.

One thing that still wasn’t clear at that point, though, is how the virus gets to the pancreas to kill the cells. Fiorina says his latest research, which has not yet been published, attempts to answer that question. His data shows that SARS-CoV-2 can be detected in the pancreatic lymph node, suggesting that it could reach that location by traveling directly through the lymphatic system or through the bloodstream.

If confirmed, Fiorina says these findings would indicate that the virus infects the pancreas directly. In the meantime, however, he adds that SARS-CoV-2 also harms the pancreas in more indirect ways.

When the immune system mounts a defense against COVID-19, it can sometimes overreact and attack indiscriminately, causing inflammation throughout the body. This can stress the pancreas and raise blood sugar levels. Meanwhile, the steroids that hospitals use to treat that inflammatory response can also make matters worse. Kathleen Wyne, an endocrinologist at the Ohio State University’s Wexner Medical Center, says that people with normal hormonal profiles and no risk factors for diabetes receive these steroids without any problems. But for those who are already susceptible to diabetes, steroids can tell the body to create so much insulin that the cells stop responding to it—which also drives up blood sugar levels.

The implications for long-term health

It hasn’t been long enough yet for scientists to fully understand the fate of the pancreas in the months after patients recover from a COVID-19 infection. But in May, Fiorina’s study showed that a third of the people who were newly hyperglycemic remained that way for at least six months after their recovery.

Jackson points out that this still amounts to a lot more diabetes diagnoses than would be expected in a year—and “that’s just the tip of the iceberg.”

“I don’t want to be alarmist at all, but we may see more long-term effects on the pancreas than you think,” Jackson says. “People don’t know what the state of their pancreas is until they have real problems.” He adds that even those who don’t have diabetes now in the months after their COVID-19 infection may still develop it in the future.

You May Also Like

SCIENCE

What is 'immune amnesia?' This long-term side effect of measles is newly relevant.

SCIENCE

RSV vaccines and preventive drugs have arrived. Which one is right for you?

SCIENCE

Now we know how COVID attacks your heart

It’s bad enough to develop a chronic disease like diabetes, which requires vigilant blood sugar level monitoring and regular insulin injections. But COVID-19 might also be silently harming the pancreas in ways that could have downstream repercussions for health.

Jackson likens it to a house catching on fire, where you’re so focused on the flames that are consuming your furniture you might not notice all the damage the smoke is causing to the structure of your home. Jackson says the virus can scar the tissues of the pancreas, which could possibly make it more susceptible to complications such as pancreatitis—chronic inflammation of the pancreas—or even pancreatic cancer.

“It’s not like having a clean wall that you can put new fresh plaster on,” he says. “You’ve got inherent problems in the architecture of the organ now that it’s damaged. So then repairing things is harder because you’re starting with a bumpy wall.”

Jackson says that damage to the pancreas could also harm nearby structures like the bile duct or the kidneys—which are typical targets for long-term complications from diabetes. According to the Mayo Clinic, about a quarter of people with diabetes eventually develop kidney disease because of damage to the blood vessels that filter waste from the blood.

But how much does the general population need to worry about these complications? That’s still up for debate.

Who is at risk?

Scientists are divided into two camps on the relationship between the pancreas and COVID-19—and Wyne is in the camp that’s skeptical the disease truly causes diabetes.

That’s because many people do recover after the acute phase of the infection. Many of her patients at OSU's Wexner Medical Center have been able to stop taking insulin soon after being discharged. Wyne also says that new diagnoses of type 1 diabetes have not increased at her clinic during the pandemic nor has she observed any evidence of a massive die-off of beta cells.

“I think the real question becomes—what happens when the inflammatory response subsides, what happens when the steroids go away?” Wyne says. “If the diabetes stays there, is that the person who was about to tip over the edge into diabetes anyway?”

She explains that people who develop diabetes post-infection may have been at risk for the disease anyway and that the stress COVID-19 put on their bodies merely sped it up. They might develop chronic diabetes or it might only be temporary, similar to the way that some people develop gestational diabetes during pregnancy only for their blood sugar levels to eventually return to normal.

“That’s been my approach with these COVID patients,” she says. “If they’re not going on diabetes medicines or only go on low doses, I’m going to tell them this is a warning sign that you’re going to have diabetes—I just don’t know when.”

Wyne points out that it will be decades before scientists can look at the population data to determine whether the pandemic had any effect on the rate of diabetes diagnoses.

In the meantime, researchers in the opposing camp admit that it’s possible some of the newly diagnoses diabetes cases may include people who were predisposed to it—and they too expect hyperglycemia to resolve among some people over time. But they point out that there’s no data suggesting otherwise either. To them, the pandemic presents an opportunity to answer a question that has plagued researchers for years: Can a virus trigger diabetes?

Solving an age-old mystery

Scientists have long hypothesized that type 1 diabetes is caused by an infection in the same way that other autoimmune diseases such as Hashimoto’s disease, a condition where the immune system attacks the thyroid, and lupus, a condition where the immune system attacks healthy tissue throughout the body, are suspected to be triggered by viruses.

But there’s never been enough evidence to prove this hypothesis. Although some people were diagnosed with diabetes in the wake of previous outbreaks of SARS and MERS, it was too rare an outcome to draw any conclusions. By infecting vastly more people, COVID-19 has made collecting this data a real possibility, says Francesco Rubino, chair of metabolic and bariatric surgery at King’s College London.

Last August, he and other leading diabetes researchers launched a global registry of patients with COVID-19-related diabetes to finally collect that information. He says not only will it have clinical implications for understanding the relationship between SARS-CoV-2 and the pancreas, but he expects it will also have broader ramifications.

“If you prove with some degree of confidence that COVID can actually cause diabetes then you have a proof of concept for a viral mechanism behind diabetes,” Rubino says.

Rubino says that registry has finally reached more than 620 cases, which his team of researchers has decided is a large enough sample size to begin an analysis of the data. He expects that for some patients on the global registry, their hyperglycemia will resolve over time. But among those with true diabetes, they’ll look to see if there are any patterns—which Rubino says could ultimately even reveal a new form of diabetes.

“The reason why so many of us are investigating this is because it could inform us not just about COVID-19—it could inform us about diabetes more broadly,” he says. “We might actually have to rethink much about what we know about diabetes if we were to find that this virus actually can alone trigger diabetes from scratch. That would be a very consequential discovery.”

Whatever the mechanism post-COVID-19 diabetes, however, Rubino says it’s important for those who have been infected with COVID-19 to remember that diabetes often strikes silently—and can have serious complications. He recommends anyone who has recovered from a coronavirus infection to be aware of the early warning signs such as fatigue, frequent urination, and inexplicable thirst and seek treatment right away.

“I think it’s not likely to be a problem for the vast majority of people who had COVID,” he says. “But if you can know earlier rather than later it’s much better for you.”