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Since early in the pandemic, physicians have flagged diabetes as a risk factor for worse outcomes with COVID infection, but the relationship may also work the other way: evidence is building that COVID could also be a risk factor for developing diabetes, both type 1 and type 2.

While the science isn't yet settled, and the exact mechanism that could drive such a relationship isn't clear, experts say there appears to be a signal that's worth continued investigation.

"The jury is still out," said Rifka Schulman-Rosenbaum, MD, of Northwell Health in New York, who also chairs the American Association of Clinical Endocrinology's Diabetes Disease State Network. "That is of course something we want to understand well, and understand the true risk related to it."

Alan Kwan, MD, a cardiologist at Smidt Heart Institute at Cedars-Sinai in Los Angeles, was the lead author on a study that found COVID infection was associated with an increased risk of new-onset diabetes -- albeit the risk appeared to be mitigated by vaccination.

Kwan and colleagues looked at records from nearly 24,000 adults who had at least one COVID infection and were treated at Cedars-Sinai from 2020 to 2022. They found in adjusted models that a history of COVID infection was associated with a 58% higher likelihood of developing new-onset diabetes compared with a new diagnosis of a benchmark condition.

But that risk appeared to be driven by unvaccinated patients, who had a 78% increased risk of developing diabetes within 90 days of infection, compared with no significant association seen for those who were vaccinated.

"We do see an association, at least, between a COVID infection and an increased risk of being diagnosed with diabetes," Kwan told 名媛直播, cautioning that it's too soon to say that COVID does indeed cause diabetes.

One plausible mechanism could be "persistent inflammation contributing to insulin resistance," Kwan and colleagues wrote in their paper, but the exact "mechanisms contributing to post-infection diabetes risk remain unclear."

Kwan and colleagues' findings are consistent with the results of a meta-analysis of nine cohort studies totaling nearly 40 million participants late last year that found COVID patients had an increased risk of both type 1 (RR 1.48, 95% CI 1.26-1.75) and type 2 diabetes (RR 1.70, 95% CI 1.32-2.19).

The BMC Medicine paper noted that physicians should pay particular attention to new-onset diabetes risk in the first 3 months after COVID infection.

In addition, a study using data from the U.S. Department of Veterans Affairs last year found a 40% increased risk of diabetes following COVID infection compared with a historical control group.

Studies focused on children have also pointed to a link between COVID infection and new-onset diabetes. Last year, that the risk of new-onset diabetes was higher for kids who'd had a COVID infection.

They theorized a handful of mechanisms by which COVID might lead to diabetes, including a viral attack on pancreatic cells expressing angiotensin-converting enzyme 2 (ACE2) receptors, stress hyperglycemia resulting from a cytokine storm and alterations in glucose metabolism caused by infection, or by pushing prediabetes into diabetes.

On the other hand, some studies have found no relationship between COVID and new-onset diabetes, including a U.K. cohort study of hospitalized patients earlier this year. Researchers found no difference in the incidence of new-onset diabetes when comparing those hospitalized with COVID versus those hospitalized with pneumonia in the years before the pandemic.

Thus, the relationship is ripe for future study, researchers said.

"There is a lot of work to be done in the area," Kwan said. "There is so much that we don't really know, and we don't really understand."

Schulman-Rosenbaum said that from "the perspective of a physician, there does seem to be something to this literature, even if it's not COVID-specific."

She noted that the workflow hasn't yet changed for physicians. For instance, doctors are not approaching patients with the mindset that, if they've had COVID, they need to get checked for diabetes.

She also noted that with less COVID in the community, and with higher levels of vaccination and greater availability of antivirals, complications may be easing.

"We're at this point in the pandemic," she said, during which "things are becoming more routine" and people are "integrating COVID into our day-to-day."

"As a physician, I definitely feel less concerned if my patient is going out and interacting; whereas, in the beginning it may have been more concerning," Schulman-Rosenbaum said. "Now, because we have vaccination there definitely is a layer of relaxation, feeling a little bit less concerned with day-to-day activities."

"COVID is not gone," Schulman-Rosenbaum cautioned. "We still have patients who come in with it." But she added, "They're not typically as sick, on the ventilators." Maybe they have pneumonia in some cases, "but not as severe."

Kwan echoed those sentiments. In the beginning of the pandemic, the concerns were transmission and acute infection, and the associated mortality, he said. Then, with more experience with COVID, "we began to see other things we weren't expecting -- long COVID, in particular, I would say."

"We are in a time where we are actively changing the way we deal with COVID, and think about COVID infection," Kwan told 名媛直播. "Trying to understand [the long-term effects] of COVID infection and the pandemic as well is where our research falls."

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