Is COVID Really Causing New-onset Type 1 Diabetes in Young People?

New research on Scottish data has found SARS-CoV-2 infection is linked to an increased incidence of new-onset type 1 diabetes in under-35s – but only in the first month after infection, likely due to increased testing as well as COVID bringing forward the progression of diabetes.

The study, presented at this year’s European Association for the Study of Diabetes (EASD) Annual Meeting, linked data on COVID tests results to the Scottish diabetes register for the period between March 2020 and November 2021, and tested whether this period of COVID infection was associated with an increased risk of diabetes.

“Our findings call into question whether a direct association between COVID and new-onset type 1 diabetes in adults and children exists”, says co-lead author Professor Helen Colhoun from Public Health Scotland and the University of Edinburgh, Scotland. “One recent report by researchers at the US Centers for Disease Control and Prevention (CDC), analysing two large insurance-claim databases of those under age 18, found that children with COVID were 2.5 times as likely to be diagnosed with diabetes over a month after infection than those who were never infected. If replicated, this is going to create a large number of people with newly diagnosed diabetes and might also alter the risk–benefit balance for COVID vaccination in young children. Importantly, we did not confirm that finding.”

In type 1 diabetes, which usually appears during childhood or adolescence, the immune system attacks insulin-producing cells, but it is not known why. One theory is that the immune system may be triggered by a viral infection and then accidentally also attacks insulin-producing cells. It has also been suggested that viral infections may increase the rate of progression of type 1 diabetes in people who still have normal blood sugar levels.

In this study, Prof Colhoun and colleagues linked individual-level data on PCR-confirmed SARS-CoV-2 infections from the Electronic Communication of Surveillance Database, which captures all PCR tests for COVID-19 nationally, with precise dates of all new type 1 diabetes diagnoses from the national register in Scotland (that is updated daily).

During the study period a confirmatory PCR test was mandatory for all those with a positive lateral flow test.

The important aspect of this study is the exact dates of diabetes diagnosis were available, unlike in some earlier studies, ensuring that the time sequence of COVID and type 1 diabetes could be established.

Between March 2020 and November 2021, a total of 365 080 children and adults had at least one detected SARS-CoV-2 infection, and 1074 were diagnosed with type 1 diabetes.

The analysis found no association between SARS-CoV-2 infection and new-onset type 1 diabetes 30 days or more after infection, or in those aged younger than 16 years, contrary to several previously reported studies.

However, the researchers did find that children and adults with a first positive SARS-CoV-2 test were 2.5 times as likely to be diagnosed with diabetes within 30 days of infection compared to those who did not have a previous registered infection; this risk was more than three times higher in those younger than 16 years.

But the authors stress strong arguments against a causal effect of COVID underlying this association.

Further analyses investigating the pattern of COVID- testing in relation to type 1 diabetes diagnosis found an increased frequency of SARS-CoV-2 testing in the days before and after diabetes presentation, for both negative and positive results. This suggests, says the authors, that the association may partly be explained by higher detection of infection at this time.

The authors also note that the average time from the onset of type 1 diabetes symptoms to diagnosis under 16s in England is around 25 days. So, it is likely that many of those who tested positive for COVID-19 within 30 days of a diabetes diagnosis already had type 1 diabetes at the time of infection.

No link was found between between COVID vaccination status and new-onset type 1 diabetes in adults (few children were vaccinated during the study period), providing further evidence against a causal effect of SARS-CoV-2 infection on the development of diabetes.

The researchers also looked at trends in type 1 diabetes incidence in Scottish children aged 0–14 years before and during the pandemic, finding that the incidence in 2020–2021 was around 20% higher than the 7-year average for 2015–2021.

However, they point out that based on estimates from England, the time course of the increase in diabetes incidence in those aged 0–14 years predated most of the cumulative incidence of SARS-CoV-2 infection in this age group (June 2021 onwards), suggesting no causal link between COVID and rates of diabetes.

“Our findings show that causes other than COVID infection itself need to be considered in relation to the increased incidence of type 1 diabetes”, said co-lead author Professor Paul McKeigue from Public Health Scotland and the University of Edinburgh, Scotland. “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.”

The authors note that although their study was large, further analyses with more recent data is needed, and that the delay in mass testing meant many COVID cases in the young went undetected.

Source: EurekAlert!