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Diabetes increases COVID-19 severity and COVID-19 creates Diabetes - Oct 2020

A Global Data Effort Probes Whether Covid Causes Diabetes Wired Magazine

Dozens of case reports have hinted that the coronavirus might trigger the onset of diabetes in people with no history of the disease.

A growing number of researchers think that the relationship between the coronavirus and diabetes is actually a two-way street.

FROM THE OUTSET of the pandemic, data coming out of early coronavirus hot spots like China, Italy, and New York City foretold that certain groups of people would be more vulnerable to Covid-19. The disease hit older people and people with underlying medical conditions the hardest. As early as February, diabetes had emerged as one of the conditions associated with the highest risk. In one large study out of China, people with diabetes were more than three times as likely to die of Covid-19 than the overall population.

But that’s not what brought four diabetes experts from Australia and the United Kingdom onto a Zoom call back in April. They were supposed to just be catching up—a virtual tea among friends. But talk soon turned to something strange that they’d been seeing in their own hospitals and hearing about through the grapevine. The weird thing was that people were showing up in Covid-19 wards, after having tested positive for the virus, with lots of sugar in their blood. These were people with no known history of diabetes. But you wouldn't know it from their lab results.

After that call, the experts reached out to colleagues in other countries to see if they’d seen or heard of similar cases. They had.

Acute viral infections of all sorts can stress the body, causing blood sugar levels to rise. So that in itself wasn’t unusual, says Francesco Rubin, a bariatric surgeon and diabetes researcher at King’s College in London, who was on that first Zoom call. “What we were seeing and hearing was a little bit different.”

Doctors around the world had described to him strange situations in which Covid-19 patients were showing symptoms of diabetes that didn’t fit the typical two-flavor manifestation of the disease. In most people with type 1 diabetes, their immune cells suddenly turn traitorous, destroying the cells in the pancreas that produce insulin—the hormone that allows glucose to exit the bloodstream and enter cells. People with type 2 diabetes have a different problem; their body slowly becomes resistant to the insulin it does produce. Rubin and his colleagues were seeing blended features of both types showing up spontaneously in people who’d recently been diagnosed with Covid-19. “That was the first clinical puzzle,” he says.

For clues to an explanation, Rubin and his colleagues looked to ACE2, the protein receptor that SARS-CoV-2 uses to invade human cells. It appears in the airways, yes, but also in other organs involved in controlling blood sugar, including the gut. Doctors in China discovered copies of the coronavirus in the poop of their Covid-19 patients. And a meta-analysis found that gastrointestinal symptoms plague one out of 10 Covid-19 sufferers.

In the last few decades, scientists have discovered that the gut is not the passive digestive organ once thought. It actually is a major endocrine player—responsible for producing hormone signals that talk to the pancreas, telling it to make more insulin, and to the brain, ordering it to make its owner stop eating. If the coronavirus is messing with these signals, that could provide a biological basis for why Covid-19 would be associated with different forms of diabetes, including hybrid and previously unknown manifestations of the disease. Rubin is one of a growing number of researchers who think that the relationship between the coronavirus and diabetes is actually a two-way street. Having diabetes doesn’t just tip the odds toward contracting a worse case of Covid-19. In some people, the virus might actually trigger the onset of diabetes, and the potential for a lifetime of having to manage it.

Take for example, three men who showed up at a hospital in the northern part of India weak, feverish, and without any history of diabetes. They all tested positive for SARS-CoV-2. And when their bloodwork came back, they all had dangerously high buildups of glucose and ketones, which the body produces when it doesn’t have enough insulin to break down sugar. The official term for the potentially deadly complication is diabeteic ketoacidosis, and it is usually seen in children with type 1 diabetes.

Mohammad Shafi Kuchay, an endocrinologist who consulted on the cases, told WIRED via email that he and the other doctors assigned to the cases assumed the virus had somehow knocked out these patients’ insulin-making cells, giving them type 1 diabetes. And so the doctors put the men on a regimen of insulin injections. But as the months went by, they needed the injections less and less. They were shifted to oral antidiabetic drugs, and have been managing like this for more than two months now. “That means the patients have type 2 diabetes,” Shafi Kuchay wrote. Whatever damage the virus caused to these patients’ insulin-secreting cells appears to be transient. More monitoring will be necessary to determine if their type 2 diabetes diagnosis is short-lived, as well.

Will other patients also find that their blood sugar problems go away when their infection resolves? Or will Covid-19 cause diabetes for life? “None of those questions could be addressed with just the anecdotal case reports that were coming out,” says Rubin. That’s why he and an international group of scientists decided to act on their hunch and establish a global repository for tracking information about the coronavirus-related diabetes.

The CoviDiab Registry allows doctors around the world to upload anonymized data about Covid-19 patients with abnormal blood sugar levels who have no prior history of diabetes. That includes the basics, like age, sex, past medical history, and details of the person’s disease progression: Do they wind up in the ICU or on a ventilator? But the registry also asks doctors to catalogue which medications they’re administering, on the off chance that it’s not the coronavirus infection that’s triggering the diabetes but an unknown side effect of something used to treat it.

The goal of this information-gathering effort is to grok the scale and scope of the problem, as well as potential solutions. How often is Covid-19 associated with new-onset diabetes? And what flavor—type 1, type 2, or a new form of the disease? What exactly causes the metabolic malfunction? How long do such cases of diabetes last, and what are the best ways to treat them? It might be a while before there’s enough data to answer questions about prevalence and mechanism. But Rubin thinks they could have information about what kinds of diabetes most frequently develop in Covid-19 patients—and what might predispose people to this particular coronavirus complication—by the end of the year.

This is not the first registry to track the overlap between people with Covid-19 and other conditions. Similar data pooling efforts spun up early this year for people with inflammatory bowel disease, chronic liver disease, and rheumatoid disorders, among others. Eric Topol, a leading cardiologist at the Scripps Research Translational Institute, has advocated for a similar approach to tracking heart complications of Covid-19. The diabetes database launched in June, and since then, more than 275 physicians have requested access to share data about at least one patient who meets the criteria. Vetting each physician contributor takes time, and after that, registry organizers have to set up data-sharing agreements that comply with Europe’s strict data protection laws. But so far, dozens of cases have been uploaded. And what’s clear, says Rubin, is that this is not just an anecdotal problem. “From what we’ve seen so far, Covid-19-related diabetes will not be a prevalent issue that affects the majority of people,” he says. “But now we know it’s a possibility, even if not a common one.”

That’s important for people to know, because diabetes can be easily managed, as long as it’s recognized. Be aware, not alarmed, says Rubin. If you’ve recently been diagnosed with Covid-19 and notice that you’re having to pee more often than usual, or are continuing to feel fatigued after you’ve recovered from other symptoms like fever, coughing, and loss of smell, that could be a good reason to ask your doctor about getting a blood test.

Provided they find funding to keep it going, Rubin and his colleagues hope to keep the registry running for years. That would allow them to investigate whether Covid-associated diabetes is a fleeting condition that passes when the infection clears or a long-term diagnosis. It could also capture situations in which the infection doesn’t cause diabetes immediately, but causes enough damage to tissues involved in metabolism that it heightens a person’s risk of developing the disease later. “We’re looking at a possible legacy effect of Covid-19,” says Rubin. “With the registry we hope to be able to look into the future, not just the present.”

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