articles

The little girl felt poorly, but both she and her mom thought they knew the reason. Aliyah Davis, just nine years old, was battling COVID. Fatigued, repeatedly sick to her stomach, with no sense of smell or taste and some shortness of breath, she seemed to have a near-textbook case of the virus.

Aliyah had a history of asthma, so her mother, Christina Ortiz, took her to the emergency department, where she was told the symptoms were likely COVID-related. But two and a half weeks later, Aliyah became sick again during the middle of the night, and Christina noted that her daughter had been experiencing insatiable thirst and frequent urination ever since that first ED visit. This time, a urine dip tested positive for ketones. Further workup revealed the issue: Aliyah had new-onset diabetes.

Her diagnosis in the summer of 2020 was the front edge of what has become a troubling and at times baffling development. Although researchers are still straining to understand why, it appears that COVID-19 and diabetes have formed an intricate—and dangerous—partnership.

It’s also a bidirectional one, says Francesco Rubino, a pioneer in diabetes surgery at King’s College in London. “The relationship appears not just one way, but two ways,” Rubino tells me.

On one side, diabetes is a key risk factor for developing serious illness or dying after catching COVID. But we now also have multiple reports of patients who contract COVID-19 and then go on to develop new-onset diabetes and sometimes severe imbalances in their blood sugar, such as diabetic ketoacidosis (DKA). In fact, a large diabetes study of adults published last month in the journal Lancet Diabetes and Endocrinology showed that individuals who recovered from COVID-19 over the last year stood a 40 percent greater chance of receiving a new diabetes diagnosis than the uninfected.

At this point, evidence is more limited in children, and there is much that we do not know. “While we are concerned that COVID might cause diabetes, we need to rule out other reasonable causes of this association that [are] not necessarily the one that links the virus to the disease,” says Rubino.

Aliyah’s blood sugar was sky-high despite having no immediate family history of diabetes, not being overweight and not having other obvious comorbidities. Her DKA diagnosis prompted a four-day hospital admission. Such diagnosis, too, is becoming more common.

Hospitalizations in children hit record highs during the surge of the Omicron variant of the SARS-CoV-2 virus. As of March 31st, over 12.8 million total pediatric COVID-19 cases had been reported in the U.S. since the start of the pandemic. Comparatively few children are hospitalized for COVID, but even a small percentage of a large number can be significant.

A new diabetes diagnosis is a serious concern with the potential to change a person’s life. As a chronic condition, it affects how the body uses blood sugar (or glucose), and it can wreak havoc years down the line. Possible complications include kidney failure, heart attacks, stroke, nerve damage, macular degeneration, blindness, vascular issues and even amputations.

With type 1 diabetes, which is usually diagnosed in children and young adults, it’s thought that one’s own immune system mistakenly attacks insulin-producing cells in the pancreas, so that the body makes little or no insulin and blood sugar levels rise. With type 2, primarily diagnosed in adulthood and far more common, one’s cells become resistant to insulin, leading to similar spikes in blood sugar levels. New-onset cases of both types have been reported during the pandemic, says Rubino, co-principal investigator of CoviDIAB, a global registry which is collecting detailed information on the topic.

Researchers at the Centers for Disease Control and Prevention (CDC), analyzing two large insurance-claim databases of those under age 18, found that children with a prior COVID infection were 31 percent to 166 percent more likely to develop diabetes than those who hadn’t had COVID-19 (or who had a different, non-SARS-CoV-2 respiratory infection). Compared to those other acute respiratory infections in particular, a new diabetes diagnosis was 116 percent more likely to occur in those who had a COVID-19 infection.

One of the earliest reports of this development came from London in 2020, where researchers found an 80 percent increase in new-onset type 1 diabetes in children during the pandemic. A study at Rady Children’s Hospital in San Diego, meanwhile, noted a 57 percent increase in children admitted with new-onset type 1 diabetes during the pandemic from March 2020 to March 2021. This study also found a higher percentage of children who presented with DKA, indicating a greater severity of disease at the time of diagnosis, according to Jane Kim, a study author and pediatric endocrinologist at the University of California, San Diego.

Reports of increasing diabetes rates in children are “in line” with several emerging observations internationally, says Paolo Fiorina, a diabetes expert and research associate at Boston Children’s Hospital–Harvard Medical School. Finnish, Romanian, Italian, German and Australian researchers all have found that more children were diagnosed with new-onset type one diabetes during the pandemic than prepandemic. At Children’s Medical Center in Dallas, pediatric endocrinologist Abha Choudhary says that type 2 cases are rising, and “these patients are sicker at presentation.”

“I do believe that COVID-19 is causing a surge” in new diabetes cases, Fiorina says. “This is clearly demonstrated now … and it’s much higher than what is observed in other viral infections such as SARS-CoV-1 and hepatitis.” Others, including Rubino, are cautious about attributing causation. “For the moment we can say that there is an association between new-onset cases of diabetes and COVID-19,” he says. “I think that’s pretty solid.” (The American Diabetes Association says a direct link is not yet clear.)

Researchers are still trying to learn the mechanisms behind a potential link. Also, the long-term connection between SARS-CoV-2 and diabetes is not well established. For that matter, type 1 and type 2 diabetes are different disease processes, Kim says. “We want to be careful in extrapolating findings from type 1 [to] type 2, and vice versa,” she says.

It’s possible, experts say, that the pandemic’s effect on our health care systems is playing a role here. Previous delays in seeking care, for example, might justify some of the increases in new diabetes cases. Says Rubino, “Is this truly new diabetes, or just newly diagnosed but preexisting diabetes?”

Some scientists theorize that COVID-19 might lead to diabetes through a direct attack of pancreatic cells. Research has shown that the coronavirus can infect insulin–producing cells in the pancreas, the so-called beta cells. Autopsy results of COVID-19 victims have confirmed viral antigen presence and even damage to some of these beta cells.

“When New York City was in the center of the pandemic in April 2020, we learned that it was very challenging to control the blood glucose level of some COVID-19 patients,” says Shuibing Chen, director of the diabetes program at Weill Cornell Medical College and an NIH-funded team researching the issue. “Then we tested different cells for their permissiveness to SARS-CoV-2. Very surprisingly, we found pancreatic beta cells can be infected.” Those cells appeared to have been transformed in the process, rendering them incapable of functioning properly.

Another NIH-funded team, this one led by Peter Jackson at the Stanford University School of Medicine, employed mass spectrometry to see that beta cells “were strongly reprogrammed by the virus to cause cell death,” Jackson says. That process, he says, could lead to new diabetes in some patients or a worsening of the condition in others. “The effects we see in vitro are so strong,” Jackson adds.

And researchers are considering other possibilities. It has long been known that with severe illness or infection, a stress response in the body can lead to high blood glucose, called hyperglycemia. The virus might also induce a cytokine storm—a whirlwind of inflammation and an overzealous immune response—that could lead to insulin resistance and beta cell dysfunction or incite an autoimmune reaction, in which one’s own defense system attacks the pancreas and makes it dysfunctional.

Another potential factor: “Children have gained weight during the COVID pandemic, likely due to lack of exercise, increased food intake and psychosocial stress,” Choudhary says. That could boost childhood obesity, which is associated with a higher risk of developing type 2 diabetes. Some patients also may have had prediabetes, which occurs in one in five adolescents, according to the CDC. In susceptible individuals, it’s possible that the infection tips the scale enough that they develop diabetes. “Viral infections can potentially be a trigger in a patient who has a predisposition,” Choudhary says.

It’s a rather exhaustive list of possibilities—even steroid medications used to treat COVID temporarily raise blood sugar levels—but vaccination rates are a part of the equation. Fiorina says that some parents’ reluctance to vaccinate their children may factor into this surge of pediatric diabetes cases, “reinforced by their incorrect thoughts that there is an evident cut-off at which younger ages mitigate increased COVID-19 risks.” Adds Kim, “As a physician dedicated to the health of all children regardless of whether they have diabetes or not, I recommend vaccination against COVID-19 and influenza for those who do not have contraindications.”

The vast majority of people who get COVID will not develop diabetes, Rubino says, and that context is important. But with treatments mostly unavailable and researchers still trying to understand the underlying causes, families need to stay vigilant and be aware of the symptoms on behalf of their children. Constant thirst, increased urination, extreme fatigue and unexpected weight loss are particular red flags.

And positive life changes can make a big difference. Since her hospitalization, Aliyah, now 11, is doing much better. She’s on an insulin regimen and she and her mother carefully monitor what she eats. While a vaccine wasn’t available when she contracted the virus, she is now fully vaccinated, her mom says.

She is also back to doing what other children her age are doing, “playing with my friends,” Aliyah says. Considering the difficult journey she has made, that is a small joy not to be underestimated.

View Original Article