Does COVID-19 Induce Type 1 Diabetes in Kids? Jury Still Out

Miriam E. Tucker

January 24, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Two new studies from different parts of the world have identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons still aren't clear.

The findings from the two studies, in Germany and the United States, align closely, endocrinologist Jane J. Kim, MD, professor of pediatrics and principal investigator of the US study, told Medscape Medical News. "I think that the general conclusion based on their data and our data is that there appears to be an increased rate of new type 1 diabetes diagnoses in children since the onset of the pandemic."

Kim noted that because her group's data pertain to just a single center, she is "heartened to see that the [German team's] general conclusions are the same as ours." Moreover, she pointed out that other studies examining this question came from Europe early in the pandemic, whereas "now both they [the German group] and we have had the opportunity to look at what's happening over a longer period of time."

But the reason for the association remains unclear. Some answers may be forthcoming from a database designed in mid-2020 specifically to examine the relationship between COVID-19 and new-onset diabetes. Called CoviDiab, the registry aims "to establish the extent and characteristics of new-onset, COVID-19-related diabetes and to investigate its pathogenesis, management, and outcomes," according to the website.

The first new study, a multicenter German diabetes registry study, was published online January 17 in Diabetes Care by Clemens Kamrath, MD, of Justus Liebig University, Giessen, Germany, and colleagues.

The other, from Rady Children's Hospital of San Diego, was published online January 24 in JAMA Pediatrics by Bethany L. Gottesman, MD, and colleagues, all with the University of California, San Diego.

Mechanisms Likely to Differ for Type 1 vs Type 2 Diabetes

Neither the German nor the US investigators were able to directly correlate current or prior SARS-CoV-2 infection in children with the subsequent development of type 1 diabetes.

Earlier this month, a study from the US Centers for Disease Control and Prevention did examine that issue, but it also included youth with type 2 diabetes and did not separate out the two groups.

Kim said her institution has also seen an increase in type 2 diabetes among youth since the COVID-19 pandemic began, but did not include that in their current article.

"When we started looking at our data, diabetes and COVID-19 in adults had been relatively well established. To see an increase in type 2 [diabetes] was not so surprising to our group. But we had the sense we were seeing more patients with type 1, and when we looked at our hospital that was very much the case. I think that was a surprise to people," said Kim.

Although a direct effect of SARS-CoV-2 on pancreatic beta cells has been proposed, in both the German and San Diego datasets the diagnosis of type 1 diabetes was confirmed with autoantibodies that are typically present years prior to the onset of clinical symptoms.

The German group suggests possible other explanations for the link, including the lack of immune system exposure to other common pediatric infections during pandemic-necessitated social distancing — the so-called hygiene hypothesis — as well as the possible role of psychological stress, which several studies have linked to type 1 diabetes.

But as of now, Kim said, "Nobody really knows." 

Is the Effect Direct or Indirect?

Using data from the multicenter German Diabetes Prospective Follow-up Registry, Kamrath and colleagues compared the incidence of type 1 diabetes in children and adolescents from January 1, 2020 through June 30, 2021 with the incidence in 2011-2019.

During the pandemic period, a total of 5162 youth were newly diagnosed with type 1 diabetes at 236 German centers. That incidence, 24.4 per 100,000 patient-years, was significantly higher than the 21.2 per 100,000 patient-years expected based on the prior decade, with an incidence rate ratio of 1.15 (P < .001). The increase was similar in both males and females.

There was a difference by age, however, as the phenomenon appeared to be limited to the pre-adolescent age groups. The incidence rate ratios (IRRs) for ages below 6 years and 6-11 years were 1.23 and 1.18 (both P < .001), respectively, compared to a nonsignificant IRR of 1.06 (P = .13) in those aged 12-17 years.

Compared with the expected monthly incidence, the observed incidence was significantly higher in June 2020 (IRR, 1.43; P = .003), July 2020 (IRR, 1.48; P < 0.001), March 2021 (IRR, 1.29; P = .028), and June 2021 (IRR, 1.39; P = .01).

Among the 3851 patients for whom data on type 1 diabetes-associated autoantibodies were available, the adjusted rates of autoantibody negativity did not differ from 2018-2019 during the entire pandemic period or during the year 2020 or the first half of 2021.  

"Therefore, the increase in the incidence of type 1 diabetes in children appears to be due to immune-mediated type 1 diabetes. However, because autoimmunity and progressive beta-cell destruction typically begin long before the clinical diagnosis of type 1 diabetes, we were surprised to see the incidence of type 1 diabetes followed the peak incidence of COVID-19 and also the pandemic containment measures by only approximately 3 months," Kamrath and colleagues write.

Taken together, they say, the data suggest that "the impact on type 1 diabetes incidence is not due to infection with SARS-CoV-2, but rather a consequence of environmental changes resulting from the pandemic itself or pandemic containment measures."

Similar Findings at a US Children's Hospital

In the cross-sectional study in San Diego, Gottesman and colleagues looked at the electronic medical records (EMRs) at Rady Children's Hospital for patients aged younger than 19 years with at least one positive type 1 diabetes antibody titer.

During March 19, 2020 to March 18, 2021, a total of 187 children were admitted for new-onset type 1 diabetes, compared with just 119 the previous year, a 57% increase.

From July 2020 through February 2021, the number of new type 1 diabetes diagnoses significantly exceeded the number expected based on a quarterly moving average of each of the preceding 5 years.

Only four of the 187 patients (2.1%) diagnosed during the pandemic period had a COVID-19 infection at the time of presentation. Antibody testing to assess prior infection wasn't feasible, and now that children are receiving the vaccine — and therefore most will have antibodies — "we've lost our window of opportunity to look at that question," Kim noted.   

As has been previously shown, there was an increase in the percentage of patients presenting with diabetic ketoacidosis during the pandemic compared with the prior 5 years (49.7% vs 40.7% requiring insulin infusion). However, there was no difference in mean age at presentation, body mass index, A1c, or percentage requiring admission to intensive care.

Because these data only go through March 2021, Kim noted, "We need to see what's happening with these different variants. We'll have a chance to look in a month or two to see the effects of Omicron on the rates of diabetes in the hospital."

Will CoviDiab Answer the Question?

Data from CoviDiab will include diabetes type in adults and children, registry co-principal investigator Francesco Rubino, MD, of King's College London, UK, told Medscape Medical News.

"We aimed at having as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c. By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible — or not — and what type of diabetes is most frequently associated with COVID-19 as this also speaks about mechanisms of action."

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or that the hyperglycemia may be stress-induced and temporary.

"We're looking at this question with a skeptical eye...Is it just an association or does the virus have a role in inducing diabetes from scratch, or can the virus advance pathophysiology in a way that it ends up in full-blown diabetes in predisposed individuals?"

While no single study will prove that SARS-CoV-2 causes diabetes, "combining observations from various studies and approaches we may get a higher degree of certainty," Rubino said, noting that the CoviDiab team plans to publish data from the first 800 cases "soon."

Kim has reported no relevant financial relationships. Rubino has reported receiving grants from Ethicon and Medtronic, personal fees from GI Dynamic, Keyron, Novo Nordisk, Ethicon, and Medtronic.

Diabetes Care. Published online January 17, 2022. Full text

JAMA Pediatr. Published online January 24, 2022. Full text

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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