Coronavirus and Diabetes: Covid-19 Tied to New Diabetes Cases
On top of posing a greater risk to people who already have diabetes, Covid-19 might trigger diabetes in people with no history of the condition.
The threat of Covid-19
While Covid-19 can pose a grave danger to almost anyone, it became clear early in the pandemic that some people face greater risk than others. That includes older patients and those with certain pre-existing health problems, from heart, lung, and kidney disease to cancer, obesity, and diabetes.
We still have a lot to learn about Covid-19, though, even as vaccines begin to help us fight back against the yearlong pandemic. After making its fateful leap to humans from some other species, the novel coronavirus has continually surprised us with the different ways it can wreak havoc in the human body.
On top of exploiting the vulnerability of people who already have diabetes, for example, research increasingly suggests Covid-19 can also lead to new diabetes in people with no history of the condition. This effect is still not well understood, and scientists are racing to learn more about it. In the meantime, here’s a closer look at what we do know about the relationship between the new coronavirus and diabetes.
Covid and pre-existing diabetes
There is no evidence to suggest people with diabetes are more likely to get Covid-19 than the general population, according to the American Diabetes Association (ADA). If they do get it, however, the threat of severe disease is higher than it would be in someone without diabetes. The risk can be compounded further if multiple risk factors overlap—a person with diabetes and heart disease, for example, may be in greater danger from Covid-19 than someone with just one of those conditions.
The two most common forms of diabetes, type 1 and type 2, both involve issues with insulin, although they develop in different ways. Insulin is a hormone made in the pancreas that allows your body to regulate blood sugar levels.
Type 1 diabetes is an autoimmune disease characterized by the body producing little or no insulin, requiring insulin injections to manage blood glucose levels. Type 2 diabetes is more common, accounting for some 90 percent of diabetes cases worldwide, and occurs because the body is unable to use its own insulin effectively.
Adults of any age with type 2 diabetes face a higher risk of severe Covid-19, according to the Centers for Disease Control and Prevention (CDC). People with type 1 or gestational diabetes (a type of diabetes that occurs during pregnancy) might face a higher risk, but the evidence is less conclusive. Covid-19 is a relatively new disease caused by a novel virus, the CDC notes, and we are still learning new things about it every day.
A two-way street
The relationship between diabetes and Covid-19 seems to be “bidirectional,” explains Francesco Rubino, MD, professor and chair of metabolic and bariatric surgery at King’s College London, who co-authored a letter in The New England Journal of Medicine last summer warning about the issue.
“On the one hand, very early on it became clear that diabetes was a predisposing condition for severe Covid or even for mortality from Covid,” Rubino says. “Diabetes is actually one of the most prevalent diseases among those who die from Covid-19.”
But then experts started to see cases of people who developed diabetes in the course of Covid-19. “Some people who had no history of diabetes were showing with full-blown diabetes at the time they were experiencing severe Covid-19,” Rubino says. Along with no personal history of diabetes, he adds, some of these cases stood out because the patients also lacked a family history and other predisposing factors.
That Covid-19 patients had undiagnosed diabetes wasn’t necessarily surprising, he notes. For one thing, diabetes is often a “silent disease,” sometimes going undetected for years, so it’s not uncommon for doctors to discover it during a checkup or hospitalization for something else. And even though Covid-19 does seem to do more than just reveal hidden cases of diabetes, there had already been observations of new-onset diabetes with other viral infections—including the related coronavirus that caused the 2002 SARS outbreak.
What was more surprising, Rubino says, was the way diabetes manifested in Covid-19 patients, both those with pre-existing diabetes as well as newly diagnosed cases. People who already had one type of diabetes, for example, were reportedly coming into hospitals with symptoms more characteristic of the other type (more on that below). “That was one sign of something potentially different than with other viruses,” Rubino says.
How common is Covid-19-related diabetes?
There are clearly many reasons to be concerned about Covid-19 and diabetes at a clinical level, but Rubino sees cause for epidemiological concern, too. Based on the scale of both diseases—about 422 million people have diabetes worldwide, and more than 100 million Covid-19 cases have been documented so far—this is like “the clash of two pandemics,” he says.
It’s still too early to speculate how often Covid-19 triggers new diabetes overall, but research has provided some hints. Among people who were hospitalized with severe Covid-19, for example, newly diagnosed diabetes appeared in 14.4 percent of cases, according to a study published in November 2020 in Diabetes, Obesity, and Metabolism. Incorporating data from eight studies and 3,700 patients, it represents “the first systematic review and meta-analysis to study the extent of newly diagnosed diabetes in Covid-19 patients,” its authors write.
Still, the analysis covered a relatively small number of studies, the authors point out, and the data came from only three countries, which could limit the global applicability. And while it may shed light on the rate of new diabetes among severe Covid-19 cases, we still know very little about the rate of Covid-19-related diabetes overall, and to what extent it might affect people with milder or even asymptomatic cases of Covid-19.
How might Covid-19 cause diabetes?
The mechanisms behind Covid-19-related diabetes remain unclear, but given what we do know about each disease individually, Rubino says, there is cause for concern.
In other viral infections, it’s believed the disease induces diabetes by triggering an autoimmune response, Rubino explains. Covid-19 might be capable of inducing diabetes the same way, he says, but there are hints that it also has another mechanism available.
“What really increased our concern about a possible cause-and-effect link between the new coronavirus and diabetes is the fact that it binds to proteins that are not unique to the airways, the lining of the airways. The virus can bind to this protein to enter cells, and this protein is actually very prevalent in different organs, including those that are crucial for the metabolism of sugars.”
ACE in the hole
That protein is angiotensin-converting enzyme 2, or ACE2, and it’s the gateway by which the novel coronavirus invades human cells. In the summer of 2020, a study in the journal Cell Stem Cell found that pancreatic endocrine cells, along with certain other cells, readily express ACE2 and are easily infected by the novel coronavirus. The virus invades both alpha and beta cells in the pancreas (which regulate glucagon and insulin, respectively), and these cells then go on to help the virus replicate.
And because infection increases cell death, “it suggests that Covid-19 patients may be at risk for new-onset diabetes,” explains study co-author Todd Evans, PhD, a professor and vice-chair for research at Weill Cornell Medical College.
There are still unanswered questions, Evans adds, including whether these cells are targeted by the virus in a patient’s body. And although ACE2 seems to play a key role in Covid-19, not all ACE2-expressing cells can be infected, suggesting more complexity than we currently understand. “So the precise rules for predicting if cells or tissues can be infected are still somewhat murky and controversial,” Evans says.
Nonetheless, the apparent capability of this coronavirus to run amok in the pancreas, as well as other organs relevant for diabetes, worries many experts. “Of course we still largely don’t know what the mechanism is,” Rubino says. “But the fact that biologically the virus has the ability to enter those tissues and organs, it is a reason for concern and of course makes the possibility that diabetes can occur through this mechanism.”
If Covid-19 does have another way to induce diabetes, that might help explain the strange presentation of diabetes reported in some Covid-19 patients. Type 1 and type 2 diabetes are normally quite distinct forms of the disease, Rubino notes, yet in some patients with acute Covid-19 and diabetes, complications emerge that are atypical for that patient’s form of diabetes.
“Someone with type 1 diabetes might come in having a very severe form of insulin resistance, which is more typical of type 2,” Rubino explains. “And other patients who had type 2 diabetes would come in with complications of diabetes like ketoacidosis [a serious condition where the body makes too many blood acids, called ketones], which is more typical of type 1. So there could be multiple mechanisms that the virus could activate, leading to forms of diabetes that are maybe not purely type 1 or pure type 2, or maybe a hybrid, or maybe an entirely new form of diabetes that is not typical.”
Rubino and his colleagues have set up a global registry of patients who have Covid-19-related diabetes, and are seeking help from doctors and researchers around the world in gathering more data. The registry, known as CoviDiab, collects anonymized data about new diabetes in Covid-19 patients experiencing hyperglycemia, or high blood sugar, but who also lack a history of diabetes.
The registry does not include identifying information about patients, Rubino points out, but it does include a lot of other important details beyond whether a patient has Covid-19 and diabetes at the same time. “We want to know exactly how Covid-19 was diagnosed, and then on the other side, the severity of the diabetes, whether it was a form of type 1 or type 2, or if there were a combination of characteristics that suggest a hybrid form,” he says. There are also other valuable data about each diabetes case, including any clues about whether the patient developed diabetes before or after Covid-19.
What to watch for
We still don’t have enough valuable data to truly understand the risk of coronavirus-related diabetes, Rubino says, but his CoviDiab registry could be the key to unlocking its secrets. In the meantime, he adds, the prospect of Covid-19-related diabetes isn’t a reason to panic, especially since we should all be avoiding the virus anyway.
“We are already concerned about Covid,” he says. “There are many things we are learning about ‘long Covid,’ and diabetes is unfortunately another issue on the table. I don’t think it’s a problem that will affect the majority of people with Covid-19. But because of the possibility of Covid to trigger or exacerbate diabetes, the patients who do have Covid-19 should be particularly vigilant about symptoms that could be associated with diabetes.”
During and after a Covid-19 infection, be alert for potential symptoms of diabetes such as frequent urination, increased hunger and thirst, or fatigue, Rubino suggests. Some of these symptoms could be related to Covid-19 itself rather than diabetes, he acknowledges, but they shouldn’t be dismissed in patients who have Covid-19 or had it in the past.
For people who have diabetes already, it remains as important as ever to avoid Covid-19. That means social distancing, wearing masks in public, and being vaccinated against Covid-19 when possible. It’s also important to treat existing diabetes, Rubino adds, since it’s possible Covid-19 could pose less risk for people whose diabetes is under better control.
- Francesco Rubino, MD, professor and chair of metabolic and bariatric surgery at King's College London
- Todd Evans, PhD, professor and vice chair for research at Weill Cornell Medical College
- Centers for Disease Control and Prevention: "COVID-19: People at Increased Risk"
- American Diabetes Association: "Diabetes and Coronavirus (COVID-19)"
- The New England Journal of Medicine: "New-Onset Diabetes in Covid-19"
- Diabetes, Obesity and Metabolism: "Proportion of newly diagnosed diabetes in COVID‐19 patients: A systematic review and meta‐analysis"
- Cell Stem Cell: "A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids"