A trio of new studies from the United States and Europe explore a possible link between COVID-19 and new-onset type 1 diabetes (T1D) in children.
A US study involving data from 14 nations finds that children and adolescents have a 72% increased risk of developing T1D in the first 6 months after COVID-19 infection. Another study, this one from Norway, yielded similar results, while a Scottish study concluded that the virus likely isn't the cause.
T1D, a failure of the pancreas to produce insulin, is typically diagnosed in children.
Causative link not established
In the US study, published today in JAMA Network Open, a team led by Case Western Reserve University researchers analyzed the electronic health records of 285,628 patients aged 0 to 9 years and an equal number aged 10 to 18 in the United States and 13 other countries who tested positive for COVID-19 or other respiratory infection from March 2020 to December 2021.
Of the 571,256 total participants, 123 (0.04%) were newly diagnosed with T1D, compared with 72 (0.03%) who had non-COVID respiratory infections, a 72% increase. In both age-groups 1, 3, and 6 months after infection, the risk of T1D was substantially higher for COVID-19 survivors than for those with other respiratory infections.
The researchers said they don't know whether SARS-CoV-2 triggers the development of T1D.
"Type 1 diabetes is considered an autoimmune disease," corresponding author Pamela Davis, MD, PhD, said in a Case Western news release. "It occurs mostly because the body's immune defenses attack the cells that produce insulin, thereby stopping insulin production and causing the disease. COVID has been suggested to increase autoimmune responses, and our present finding reinforces that suggestion."
Davis advises families with a high risk of T1D to look for diabetes symptoms after COVID-19 infection and pediatricians to be on the lookout for a surge of new T1D cases, particularly amid circulation of the highly transmissible Omicron variant.
"We may see a substantial increase in this disease in the coming months to years," she said. "Type 1 diabetes is a lifelong challenge for those who have it, and increased incidence represents substantial numbers of children afflicted."
In the release, study coauthor Rong Xu, PhD, called for future research into whether the elevated risk of T1D persists, which patients are most at risk, and the treatment of COVID-associated T1D. "We are also investigating possible changes in development of type 2 diabetes in children following SARS-CoV2 infection," she said.
63% higher relative risk in Norway
An observational nationwide study of 1.2 million Norwegian children in the first 2 years of the pandemic finds that 0.13% of children and teens were diagnosed as having T1D 1 month or more after COVID-19 infection, versus 0.08% in uninfected children, a 63% increase in relative risk.
The research, conducted by Norwegian Institute of Public Health investigators and colleagues, was presented this week at the European Association for the Study of Diabetes (EASD) Annual Meeting in Stockholm, Sweden. The team used national health registers to identify new T1D diagnoses among 1,202,174 children younger than 18 years from Mar 1, 2020, to the same date in 2022.
During the study period, 424,354 children tested positive for COVID-19, and 990 were diagnosed as having T1D.
In a Diabetologia news release, lead author Hanne Lovdal Gulseth, MD, PhD, said that the results suggest a link between COVID-19 and T1D, but the risk is low. "The absolute risk of developing type 1 diabetes increased from 0.08% to 0.13%, and is still low," she said.
"The vast majority of young people who get COVID-19 will not go on to develop type 1 diabetes but it is important that clinicians and parents are aware of the signs and symptoms of type 1 diabetes," Gulseth said. "Constant thirst, frequent urination, extreme fatigue and unexpected weight loss are tell-tale symptoms."
The researchers noted that T1D has long been suspected of being an outsized immune response, perhaps to a viral infection, although a link with SARS-CoV-2 hasn't been established.
"It's possible that delays in seeking care because of the pandemic might explain some of the increases in new cases," Gulseth said.
"However, several studies have shown that SARS-CoV-2 can attack the beta cells in the pancreas that produce insulin, which could lead to development of type 1 diabetes. It's also possible that inflammation caused by the virus may lead to exacerbation of already existing autoimmunity."
Artifact of increased COVID testing?
In other research presented at EASD, a team led by University of Edinburgh and Public Health Scotland investigators evaluated Scottish diabetes registry data on 1.8 million people younger than 35 years from March 2020 to November 2021. The study was published Jul 12 in Diabetes Care.
During the study period, 365,080 children and young adults tested positive for COVID-19 at least once, and 1,074 were diagnosed with T1D. COVID-19 was associated with a rate of new-onset T1D 2.5 times that of uninfected participants and 3 times as high in children younger than 16 years, but only for 1 month.
The researchers said that the increase in T1D diagnoses after COVID-19 infection is likely an artifact of increased COVID-19 testing at the time of the T1D diagnoses rather than SARS-CoV-2 itself. Also, because the average time from onset of T1D symptoms to diagnosis is about 25 days in patients younger than 16 in England, many of those who tested positive for COVID-19 within 30 days of a diabetes diagnosis probably already had T1D, they said.
"Our findings call into question whether a direct association between COVID-19 and new-onset type 1 diabetes in adults and children exists," corresponding author Helen Colhoun, MD, MPH, said in another Diabetologia news release.
But if the research findings are replicated, she said, "this is going to create a large number of people with newly diagnosed diabetes and might also alter the risk–benefit balance for COVID-19 vaccination in young children."
In the release, Paul McKeigue, MBBCh, PhD, said that other possible causes of increases in T1D need to be explored. "We need to consider what has happened regarding the spread of viruses such as enteroviruses during the pandemic, and whether there are any other environmental factors, such as sunlight exposure and vitamin D levels, that might have altered during lockdown that might also be relevant," he said.