Why Did Type 1 Diabetes Rise Early in the COVID-19 Pandemic?

Both the incidence of type 1 diabetes and the severity at presentation rose among children and adolescents in Finland during the first 18 months of the COVID-19 pandemic, but it’s unclear whether this was due to the SARS-CoV-2 virus itself, as few had confirmed infections prior to diagnosis.

“Our results suggest that the increase in the disease rate and in the frequency of diabetic ketoacidosis are related to the preventive measures introduced at the start of the pandemic, such as lockdown and physical distancing, rather than a direct effect of SARS-CoV-2,” Mikael Knip, MD, of New Children’s Hospital, Helsinki, Finland, and colleagues write in The Lancet Diabetes & Endocrinology.

However, in an accompanying editorial, Daniel Chan, MBBS, and Jan Hau Lee, MBBS, of KK Women’s and Children’s Hospital, Singapore, point out that up to a quarter of the study population didn’t undergo SARS-CoV-2 testing.

And they note that the virus has been linked to the development of type 1 diabetes in previous studies, which have also shown that “children might not necessarily have 100% seropositivity because of T-cell response heterogeneity.”

Asked for comment, Paul Zimmet, MBBS, MD, PhD, professor of diabetes at Monash University, Melbourne, Australia, said: “It’s a very interesting study in the light of Finland having the highest incidence of type 1 diabetes globally, so it is a great place to address the relationship of SARS-CoV-2 with new diabetes.”

However, he added, “While the authors’ interpretation of causation is that lockdowns may play a role, my own view is that there is also an effect of the virus, either through inflammation or even a direct destructive effect on the pancreatic beta cells.”

Zimmet, who co-chairs a global registry aimed at establishing the links between COVID-19 and diabetes, also noted: “There is still much to learn about SARS-CoV-2 and its destructive ways, and there is a lot of disagreement between ‘experts’ on the diabetes and COVID issue and the extent to which the virus has a role.”

“There is certainly evidence that even mild SARS-CoV-2 infections increase the risk of type 2 diabetes. That in itself needs close longitudinal monitoring over time.”

Type 1 Diabetes More Frequent, Severe During COVID-19

Knip and colleagues compared data from the Finnish Pediatric Diabetes Register for the period of March 1, 2020, through August 31, 2021, with those of the same periods for the years 2014-2019. A total of 785 children younger than 15 years old were diagnosed during the 18-month pandemic period, and a total of 2096 were diagnosed during the combined 54-month reference period.

The incidence of type 1 diabetes was 61.0 per 100,000 population younger than 15 years during the pandemic, significantly higher than the 52.3 per 100,000 seen during the reference period. Comparing the two periods, the age- and sex-adjusted incidence rate ratio was 1.16, which was significant (P < .0006).  

Significantly more children had diabetic ketoacidosis at diagnosis during the pandemic (30.8% vs 22.6%; P < .001), with a significantly greater frequency of severe ketoacidosis at type 1 diabetes presentation (8.8% vs 5.6%; P = .009).

More of those diagnosed with type 1 diabetes during the pandemic tested positive for glutamic acid decarboxylase antibodies at diagnosis (P < .001) compared with those diagnosed prepandemic.

Of the 583 children in whom SARS-CoV-2 antibodies were analyzed, comprising 25.7% of those diagnosed with type 1 diabetes, only 5 (1%) were considered to have had an acute COVID-19 infection prior to the diagnosis based on two different antibody tests.

The Virus May Be to Blame, but So Might Lockdown

In the discussion section, Knip and colleagues point to previous studies showing no association between SARS-CoV-2 infection and type 1 diabetes-related islet autoimmunity.

And, they add, preliminary data suggest that the rate of type 1 diabetes has decreased in Finnish children since the pandemic lockdown was lifted in the summer of 2021. There were 211 new cases registered between September 2021 and February 2022, compared with 301 from March 1, 2020, to August 31, 2021.

“According to what is known as the biodiversity hypothesis, microbial exposure and infections in early childhood can boost the protection against autoimmune diseases. The reduction in contacts in connection with the societal lockdown significantly reduced acute infections in children, which may have increased the risk of developing [type 1] diabetes,” Knip explained in a press release from his institution.

On the other hand, Chan and Lee write, “The association observed in the study should not be equated to being causative, especially without biomarkers or comparisons of microbiota that could potentially substantiate the biological plausibility of this observation. The exact mechanisms to explain how social isolation measures affect biodiversity have yet to be examined.”

Knip, Chan, Lee, and Zimmet have  reported no relevant financial relationships.

Lancet Diabetes Endocrinol. 2023;11:251-260, 220-222. Full text, Editorial

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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