Researchers Identify Link Between COVID-19 and New Diabetes Cases

Healthcare  professionals and scientists are concerned that the coronavirus could be destroying key cells needed for the production of insulin. Find out what we know — and what still needs to be uncovered.

Link-Between-COVID-19-and-New-Diabetes-Cases-1440x810
The relationship between diabetes and COVID-19 may be more complex than scientists first suspected.Aryo Hadi/iStock; Olga Inep/iStock

One of the mysteries of COVID-19 is why the infection can cause extreme reactions, such as a life-threatening inflammatory response, high fevers, and breathing issues in some people, while other individuals experience few or no symptoms at all.

Part of that focus centers on a disturbing trend that has critical care doctors and endocrinologists searching for clues — and answers — about why some individuals with COVID-19 suddenly develop type 1 and type 2 diabetes.

Initially when the pandemic started in 2020, doctors noticed that a high percentage of COVID-19 patients had diabetes, Mihail Zilbermint, MD, an associate professor of clinical medicine at the division of endocrinology, diabetes, and metabolism at the Johns Hopkins School of Medicine in Baltimore. “At first this was observed in China because those were the majority of patients who were initially hospitalized,” he says.

Originally, the thought was that diabetes would only increase the risk of getting or having a more severe case of COVID-19, but now it appears as though there may be some sort of bidirectional relationship between diabetes and COVID-19, says Dr. Zilbermint. “We are still not sure what’s happening because it’s all new,” he adds.

A bidirectional relationship is when two conditions influence or increase the likelihood of the other in both directions.

“I am seeing an increase in the number of adults in my clinic who are newly diagnosed with diabetes, and I hear that many of my pediatric colleagues have also seen an increase in the number of children diagnosed with type 1 diabetes during the pandemic,” says Zilbermint.

According to an analysis published in November 2020 in the journal Diabetes, Obesity, and Metabolism, as many as 14.4 percent of people hospitalized with severe COVID-19 were newly diagnosed with diabetes.

More recently, data published in the Centers for Disease Control and Prevention's (CDC) Morbidity and Mortality Weekly Report in January 2022 found that youth under 18 years old were up to 2.6 times more likely to receive a new diabetes diagnosis in the 30 days after a COVID-19 infection.

How Type 1 and Type 2 Diabetes Develop

In simple terms, when a person has type 1 diabetes, their body isn’t producing the insulin needed to regulate blood sugar, says Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism, and a professor of diabetes and metabolic diseases at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “Insulin is made by very specific cells in the pancreas called beta cells,” he explains.

In type 1 diabetes that’s not related to COVID-19, the beta cells die off for reasons that are immunologic, meaning the body's immune system attacks and destroys those beta cells so they can’t make insulin, says Dr. Lazar.

Outside of COVID-19, it’s thought that the triggers for why that happens are typically a combination of genetics and environmental factors such as a viral infection; even flu-like syndromes are tied to new cases of type 1 diabetes, which is not preventable, he says.

“Type 2 diabetes is a bit more complicated,” Lazar adds. The hallmark of this type of diabetes is insulin resistance, which means the body doesn’t respond normally to insulin. Several factors — from genetics and ethnicity to lifestyle choices and weight — are related to insulin resistance, as the Centers for Disease Control and Prevention (CDC) notes.

When that happens and blood sugar remains unstable, those beta cells that make insulin have to push out more insulin and eventually they become impaired, and they can’t make enough insulin to control blood sugar, he says.

How COVID-19 May Be Triggering Type 1 Diabetes in Some People

As mentioned, scientists have long known that exposure to viruses can be a possible trigger for type 1 diabetes, and they have no reason to believe that the virus that causes COVID-19 is any different.

“If a person had a predisposition for type 1 diabetes, COVID-19 can trigger it,” says Lazar. But there seems to be something unique about the way the novel coronavirus attacks the body that may be activating diabetes even more than your typical virus, he says. “We don’t know anything for certain yet — this is the topic of a lot of research.”

The theory involves a cellular receptor called angiotensin-converting enzyme 2, commonly called ACE2 receptor. This is the protein that allows the coronavirus to infect human cells. ACE2 receptors are located in many parts of the body: the upper and lower respiratory tract, the heart, the kidneys, and parts of the gastrointestinal tract.

The SARS-CoV-2 virus (or the so-called novel coronavirus), which causes COVID-19, binds to ACE2 before it enters and infects the cells, according to the Children’s Hospital of Philadelphia.

The ACE2 receptor is also located on and in those cells of the pancreas. If a person gets infected and has the virus in their body, it appears that the virus can enter the pancreas and seek out those cells and destroy them, says Lazar. “That doesn't happen to everyone. We are still trying to figure out the real numbers on this,” he says.

King’s College of London and Monash University have created a global registry of COVID-19 cases related to diabetes, and more than 370 doctors around the world have contributed data to the effort.

The research that's ongoing is trying to uncover a few things, explains Lazar. “If this is indeed happening, what makes a person susceptible? Is it something based on their genetics or something else?” he asks.

Investigators are also trying to learn more about the insulin-producing beta cells in the pancreas, says Lazar. “Yes, they appear to have the receptor that lets the virus in that is undoubtedly contributing, but is there something else about the virus and the way it attacks cells?”

How COVID-19 May Be Leading to New Type 2 Diabetes Cases

COVID-19 may be contributing to the development of type 2 diabetes in some people in a couple of ways, says Lazar. “If you kill all the beta cells, you have type 1 diabetes. If just some of the beta cells are killed, the average person can probably still make it up — we have spare beta cells. But if a person has prediabetes, the beta cells are already working harder to begin with to keep up with insulin resistance,” Lazar says. The destruction of some beta cells in those people could be linked with a new diagnosis of type 2 diabetes, he adds.

COVID-19 May Be Unmasking Underlying Prediabetes or Borderline Diabetes

About 1 in 3 adults has prediabetes, according to the CDC. In prediabetes, blood sugar levels are higher than normal but not high enough for a diagnosis of diabetes. “If you have prediabetes, you’re at increased risk for developing diabetes,” says Zilbermint.

“Factors associated with prediabetes are being overweight or obese and over the age of 45,” says Zilbermint. Black Americans and Hispanic Americans are also more likely to have prediabetes and type 2 diabetes, he adds. “Coincidentally, those are the patients who have been shown to have worse COVID-19 outcomes,” he says.

It’s possible that some of these people who develop diabetes after becoming infected with COVID-19 had underlying or borderline diabetes and were further stressed by severe illness, says Zilbermint. “It’s like the straw that breaks the camel’s back,” he adds.

According to CDC, more than 80 percent of Americans with prediabetes don’t know they have it. Plus, an estimated 23 percent of people with type 2 diabetes are undiagnosed, according to the agency.

Will Diabetes-Related COVID-19 Be Temporary?

If a person has prediabetes and then develops diabetes after getting ill with COVID-19, do they go back to just having prediabetes after they recover or are they now “converted” to having diabetes? Irl Hirsch, MD, a researcher and professor of medicine in the division of metabolism, endocrinology, and nutrition at UW Medicine in Seattle, wants to know the answer to this question. “We don’t have the longitudinal data that we need to know that yet,” he adds.

It’s been observed that people with well-managed diabetes without insulin who become ill with COVID-19 and need insulin therapy during their hospitalization may go back to stabilizing their blood sugars successfully once they recover, says Dr. Hirsch.

Type 1 diabetes, which requires insulin treatment to replenish insulin loss, is currently not reversible.

Using Steroids to Treat Severe COVID-19 Saves Lives but Can Create a 'Bad Loop'

Another mechanism by which COVID-19 may be contributing to new cases of diabetes is not the disease itself but the way it is treated. In particular, researchers are investigating how a powerful anti-inflammatory drug may be playing a role.

The drug dexamethasone is capable of reducing deaths from a SARS-CoV-2 infection, as shown in the RECOVERY trial, where researchers observed the corticosteroid lowered deaths by up to one-third in hospitalized patients with severe COVID-19. In September 2020, the World Health Organization issued guidelines that “strongly” recommend corticosteroids such as dexamethasone be given orally or intravenously for the treatment of patients with severe and critical COVID-19.

Dexamethasone is not typically used for other severe respiratory infections, Lazar explains. “In fact, since it depresses the immune system, it can make bacterial pneumonia worse by blocking the body's immune response. Its benefit in treating COVID-19 pertains to the massive immune activation that occurs, which is combated by the dexamethasone,” Lazar says.

The good news is that the drug saves lives, Lazar says. “The bad news is that this very potent steroid exacerbates that same issue of insulin not working well,” he adds, referring to insulin resistance. When someone is already predisposed to diabetes and takes dexamethasone, the likelihood of developing high blood sugar, or hyperglycemia, increases.

Diabetes screening includes checking a patient’s health history to see if they already have a diagnosis and measuring their blood glucose, says Lazar. “Every hospitalized patient has blood glucose measured, and so the doctors know if it's in diabetic range,” he says.

Even in someone who has elevated blood sugar, the benefits of dexamethasone may outweigh the risks, especially when considering that blood glucose can be controlled in the hospital with insulin, says Lazar. “If the blood glucose is already high, the doctors would be alerted to the likely need to add insulin or increase the dose if the patient is already taking it,” he says.

Still, it can be a “bad loop,” says Lazar. “A person’s diabetes or prediabetes puts them at a higher risk for COVID-19; then they get treated with dexamethasone.” After that, their blood sugar levels become progressively higher — and that can make COVID-19 worse, explains Lazar, referring to the established link between diabetes and severe COVID-19 infection.

Worsening blood sugar control associated with the treatment is typically temporary, he says. “It is unlikely that the dexamethasone treatment would have long-term implications on diabetes, except in uncommon situations where the patient cannot be weaned off the dexamethasone,” says Lazar.

SARS Was Also Linked to an Increase in Diabetes

Part of what makes the ACE2 receptor theory seem plausible is that data from the 2003 outbreak of the severe acute respiratory syndrome (SARS) coronavirus shows that the SARS virus attacked the ACE2 proteins, including the beta cells, says Zilbermint.

A previous study published in Acta Diabetologica found that the virus “may damage islets and cause acute insulin-dependent diabetes mellitus.” The islets contain several types of cells, including beta cells. In this population, diabetes occurred during the hospitalization of 20 of 39 patients who did not receive steroid treatment. However, after three years of follow-up, only two of the people still had diabetes, which suggested the damage that the SARS virus caused was temporary, according to the authors.

Of Mice and Men: Researchers Test COVID-19’s Impact on Diabetes in Mice, but Will It Translate to Humans?

“We’re trying to find out how frequently this is occurring; we just don’t know enough about the numbers to understand the magnitude of this. We also need to find out if [type 2 diabetes] is reversible when people get better from COVID-19,” says Lazar.

Scientists have a lot of tools now for really diving in at a very deep scientific level to ask what it is about those cells that make insulin that allows the virus to penetrate to destroy them, says Lazar. “If we were to find that out, we might be able to prevent this from happening,” he says.

Scientists have a long way to go in terms of really understanding this in humans, says Lazar. “We get a lot of information from studies in mice because of how easily that can be done. It's not so easy to study human pancreases and human beta cells, and a lot of that ends up being from autopsy studies,” he says. A big question that will influence the progress and success of the research is if COVID-19 impacts the cells of the pancreas in humans in the same way it effects mice, he adds.

Concerned That You May Develop Diabetes During the Pandemic? Here’s What to Do

If you have a family history of diabetes or have risk factors for prediabetes or diabetes, there are a few things you can do to reduce your risk of developing these conditions, says Lazar. The following steps may be helpful to take regardless of potential infection with the coronavirus:

  • Develop healthy habits. Although it’s not a quick fix, talk with your doctor about strategies for achieving a healthy weight by eating well and exercising.
  • Get screened. Find out if you have diabetes or prediabetes by requesting a fasting blood glucose test with your primary care doctor. “A lot of people have one of these conditions already and they just don’t know it,” says Lazar.

The American Diabetes Association has a risk test for prediabetes that you can take online, says Hirsch. You may assess your risk by answering a handful of simple questions, he says.

And of course, take steps to help prevent infection from the coronavirus in the first place. The CDC recommends continued physical distancing, crowd avoidance, frequent handwashing, and wearing a face covering.

Additional reporting by Lisa Rapaport.