(ORDO NEWS) — The little girl felt unwell, but both she and her mother thought they knew the reason. Alia Davis, who was only nine years old, was battling COVID. Fatigue, constant nausea, lack of smell and taste, shortness of breath – it seemed that she had almost a textbook on viruses.
Aaliyah had asthma so her mother, Christina Ortiz, took her to the emergency room, where she was told her symptoms were most likely related to COVID.
But two and a half weeks later, Aliya fell ill again in the middle of the night, and Kristina noted that her daughter had experienced unquenchable thirst and frequent urination since her first visit to the ER. This time, a urine test showed a positive result for ketones. Further examination revealed a problem: Aliya had a new type of diabetes.
Her diagnosis in the summer of 2020 was the first frontier in what has become unsettling and at times puzzling. While researchers are still trying to understand the cause, it appears that COVID-19 and diabetes have formed a complex and dangerous partnership.
It is also bidirectional, says Francesco Rubino, a pioneer in diabetes surgery at King’s College London. “The relationship is not one but two ways,” Rubino tells me.
On the one hand, diabetes is a key risk factor for developing serious illness or death after contracting COVID. But now we also have numerous reports of patients who contract COVID-19 and then develop new diabetes and sometimes serious blood sugar disorders such as diabetic ketoacidosis (DKA).
In fact, a large adult diabetes study published last month in the Lancet Diabetes and Endocrinology found that people who recovered from COVID-19 within the past year were 40 percent more likely to receive a new diabetes diagnosis than those who were not infected.
Data on children is more limited at the moment, and there is much we do not know. “While we are concerned that COVID may cause diabetes, we need to rule out other reasonable causes for this association that [do not] necessarily link the virus to the disease,” Rubino says.
Aliya’s blood sugar was very high despite no immediate family history of diabetes, no overweight, and no other obvious comorbidities. The diagnosis of DKA resulted in a four-day hospitalization. This diagnosis is also becoming more common.
The number of hospitalizations among children reached a record level during the outbreak of the micron variant of the SARS-CoV-2 virus. As of March 31, more than 12.8 million cases of COVID-19 in children have been reported in the United States since the start of the pandemic. A relatively small number of children are hospitalized due to COVID, but even a small percentage of a large number can be significant.
A new diagnosis of diabetes is a serious problem that can change a person’s life. As a chronic disease, diabetes affects how the body uses blood sugar (or glucose) and can wreak havoc for years to come. Possible complications include kidney failure, heart attacks, stroke, nerve damage, macular degeneration, blindness, vascular problems, and even amputations.
In type 1 diabetes, which is commonly diagnosed in children and young adults, the body’s own immune system is thought to mistakenly attack insulin-producing cells in the pancreas, causing the body to produce little or no insulin, and blood sugar levels to rise.
In type 2 disease, which is diagnosed mostly in adulthood and is much more common, the body’s cells become resistant to insulin, which leads to similar spikes in blood sugar levels. New cases of both types have been reported during the pandemic, says Rubino, one of the principal investigators of CoviDIAB, a global registry that collects detailed information on the topic.
Researchers at the Centers for Disease Control and Prevention (CDC) analyzed two large databases of claims for under-18s and found that children with prior COVID infection were 31% to 166% more likely to develop diabetes than those without who have not had COVID-19 (or have had another respiratory infection not related to SARS-CoV-2).
Compared to other acute respiratory infections, those who had had a COVID-19 infection were 116% more likely to be diagnosed with diabetes again.
One of the earliest reports of such a development came from London in 2020, where researchers found an 80 percent increase in new cases of type 1 diabetes in children during the pandemic. At the same time, a study conducted at Rady Children’s Hospital in San Diego noted a 57 percent increase in the number of children hospitalized with new type 1 diabetes during the pandemic from March 2020 to March 2021.
According to Jane Kim, study author and pediatric endocrinologist at the University of California, San Diego, the study also found a higher percentage of children with DKA, indicating greater disease severity at diagnosis.
Reports of rising rates of diabetes in children are “consistent” with some new international observations, says Paolo Fiorina, a diabetes expert and research fellow at Boston Children’s Hospital – Harvard Medical School.
Finnish, Romanian, Italian, German and Australian researchers found that more children were diagnosed with type 1 diabetes during the pandemic than before the pandemic. At the Dallas Children’s Medical Center, pediatric endocrinologist Abha Chowdhary says cases of type 2 diabetes are on the rise and “these patients are more painful on admission.”
“I do believe that COVID-19 is causing an upsurge” in new cases of diabetes, Fiorina says. “This is clearly demonstrated now … and it is much higher than what is seen in other viral infections such as SARS-CoV-1 and hepatitis.”
Others, including Rubino, are wary of attributing causality. “At this point, we can say that there is a link between new cases of diabetes and COVID-19,” he says. “I think it’s pretty reliable.” (The American Diabetes Association says the direct link is not yet clear.)
Researchers are still trying to understand the mechanisms behind the potential connection. In addition, a long-term relationship between SARS-CoV-2 and diabetes has not been established. According to Kim, type 1 and type 2 diabetes are different diseases. “We want to be careful when extrapolating from type 1 diabetes [to] type 2 diabetes and vice versa,” she says.
Perhaps, experts say, the impact of the pandemic on our health systems is playing a role here. For example, delays in seeking care may justify some increase in new cases of diabetes. Rubino says, “Is this really new diabetes, or just newly diagnosed but existing diabetes?”
Some scientists suggest that COVID-19 may lead to diabetes through a direct attack on pancreatic cells. Studies have shown that the coronavirus can infect the insulin-producing cells of the pancreas, the so-called beta cells. Autopsy results from COVID-19 victims confirmed the presence of a viral antigen and even damage to some of these beta cells.
“When New York was at the center of the pandemic in April 2020, we learned that blood glucose levels in some patients with COVID-19 were very difficult to control,” says Shuibing Chen, director of the diabetes program at Weill Cornell Medical College and research team funded by NIH.
“Then we tested different cells for their susceptibility to SARS-CoV-2. Very surprisingly, we found that pancreatic beta cells can be infected.” It turned out that these cells had been transformed in the process, rendering them unable to function properly.
Another NIH-funded group, led by Peter Jackson of Stanford University School of Medicine, found using mass spectrometry that beta cells “were heavily reprogrammed by the virus, resulting in cell death,” says Jackson. This process, he says, could lead to the development of diabetes in some patients or worsening of the condition in others. “The effects we see in vitro are so powerful,” adds Jackson.
Researchers are looking at other possibilities as well. It has long been known that during severe illness or infection, the body’s stress response can lead to an increase in blood glucose levels, which is called hyperglycemia.
The virus can also trigger a cytokine storm – a whirlwind of inflammation and an overactive immune response – that can lead to insulin resistance and beta cell dysfunction, or trigger an autoimmune reaction in which the body’s own defense system attacks the pancreas and causes it to malfunction.
Another potential factor: “Children gained weight during the COVID pandemic, likely due to lack of exercise, increased food intake and psychosocial stress,” Chowdhary says. This could exacerbate childhood obesity, which is associated with a higher risk of developing type 2 diabetes.
“Some patients may also have had prediabetes, which affects one in five teens, according to the Centers for Disease Control and Prevention. In susceptible individuals, infection can be so debilitating that they develop diabetes. “Viral infections could potentially be a trigger in patients with a predisposition,” says Chaudhary.
That’s a pretty exhaustive list of possibilities – even the steroid drugs used to treat COVID temporarily raise blood sugar levels – but vaccination rates are part of the equation.
Fiorina says some parents’ reluctance to vaccinate their children may be contributing to this surge in childhood diabetes cases, “reinforced by their misconceptions that there is a clear cutoff at which younger age reduces increased risk of COVID-19.”
Kim adds: “As a doctor who cares about the health of all children, whether they have diabetes or not, I recommend the COVID-19 and influenza vaccinations for those who have no contraindications.”
The vast majority of people who contract COVID do not develop diabetes, Rubino said, and that context is important. But with treatment largely unavailable and researchers still trying to understand the underlying causes, families need to remain vigilant and alert to symptoms to protect their children. Constant thirst, frequent urination, extreme fatigue and unexpected weight loss are particular warning signs.
And positive changes in life can significantly change the situation. After being hospitalized, Aliya, now 11 years old, has gotten much better. She takes insulin and she and her mother are very careful about what she eats. Although there was no vaccine yet when she contracted the virus, she is now fully vaccinated, her mother says.
She’s also gone back to doing what other kids her age do – “playing with my friends,” Alia says. Considering what a difficult path she has come through, this is a small joy that should not be underestimated.
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