Type 1 diabetes is an autoimmune disease leading to an impaired glucose metabolism and requires life-long administration of insulin. While the cause of the autoimmunity reaction is still unclear, viral infections in young children are proposed to be critical environmental factors leading to type 1 diabetes. An international team of researchers from the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) now reports an increase in the incidence of islet autoimmunity in young children with a genetic risk for type 1 diabetes who had a SARS-CoV-2 infection. The findings were published in the journal JAMA.

Type 1 diabetes is an autoimmune disease. In this condition, the immune system reacts against and eventually destroys islet beta cells in the pancreas. These cells are responsible for producing insulin, a hormone that is vital for regulating glucose levels and for maintaining the body’s energy requirements. Both genetic and environmental factors are involved in the pathogenesis of the autoimmunity with viral infections being one of the factors thought to increase the risk of developing type 1 diabetes. With the outbreak of the COVID-19 pandemic, there was an increase in the incidence of type 1 diabetes. However, it was not clear if this was due to a SARS-CoV-2 infection and if infection led to an increase in islet autoimmunity.

“We had a chance to follow children from the Primary Oral Insulin Trial (POInT) and link the timing of SARS-CoV-2 infection to the appearance of islet autoantibodies,” explains Marija Lugar from the Center for Regenerative Therapies Dresden (CRTD) and Faculty of Medicine Carl Gustav Carus at TUD Dresden University of Technology, the author of the study.

POInT is a study conducted in Germany, Poland, Sweden, Belgium, and the UK. It is led by Prof. Anette-Gabriele Ziegler from Helmholtz Munich Institute of Diabetes Research and the Technical University of Munich School of Medicine. POInT recruited babies from 2018 to 2021 with a genetically defined risk for developing islet autoantibodies of at least 10%.

Risk of Developing Islet Autoantibodies Increased After SARS-CoV-2 Infection

Autoantibodies against pancreatic islets are the first sign of type 1 diabetes and indicate the start of the disease. To establish if SARS-CoV-2 infection influenced the development of early signs of type 1 diabetes, the researchers tested for islet autoantibodies and SARS-CoV-2 antibodies in two to six-month intervals from age 4 to 24 months in 885 children. 170, or almost 20% of these children, developed antibodies to SARS-CoV-2 during the pandemic indicating that they had been infected with the virus. The frequency of children who developed islet autoantibodies was over twice as high in children who had a SARS-CoV-2 infection compared to those without the infection. “The timing of the islet autoantibody appearance in relation to the SARS-CoV-2 infection in these children was striking. The most remarkable finding, however, was that the risk of developing islet autoantibodies was highest in the children who were infected before they were 18 months old, and in particular at around one year of age,” explains Prof. Ezio Bonifacio, research group leader at the CRTD and senior author of the study. “These children had around 5- to 10-fold higher risk for developing islet autoantibodies that lead to type 1 diabetes later in life. It is such a critical age for children who are genetically at risk for the disease and key to why we were able to see the association.”

Prior studies had found a correlation between type 1 diabetes incidence and COVID-19 diagnosis, but this is the first to associate SARS-CoV-2 infection with the start of islet autoimmunity.

Further Studies Needed to Determine the Potential for Prevention

It is important to note that although there was a clear temporal association between SARS-CoV-2 infection and the development of islet autoantibodies, many children developed islet autoantibodies without COVID-19.

“Type 1 diabetes is not a one-factor disease,” says Ezio Bonifacio. “However, this study again shows the link between a virus infection and type 1 diabetes right at the very start of the process and at the critical age of susceptibility.”

Although the exact mechanism behind the increased risk for islet autoimmunity in young children is unknown, the findings may help find ways to prevent type 1 diabetes.

“Since there is a vaccine available, it begs the question as to whether vaccination against viruses associated with islet autoimmunity could be an avenue for prevention of at least some cases of type 1 diabetes,” says Anette-Gabriele Ziegler. “Type 1 diabetes is a lifelong disease affecting millions of children and adults worldwide. We are convinced that investing into early prevention strategies such as those tested in GPPAD, is important to curtail the rising incidence of this disease in children.“

About the Global Platform for the Prevention of Autoimmune Diabetes
The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) is a consortium of several European research institutions in Belgium, Germany, Poland, Sweden, and the UK conducting type 1 diabetes primary prevention trials. With joint forces, the researchers identify children who have a high genetic risk for developing type 1 diabetes and offer the families to participate in one of the prevention studies POInT and SINT1A. The POInT study aims to train the immune system by oral administration of insulin and by this prevent type 1 diabetes in children with an increased genetic risk for the disease. GPPAD is coordinated at Helmholtz Munich under the leadership of Anette-Gabriele Ziegler.

About the Center for Regenerative Therapies Dresden (CRTD)
The Center for Regenerative Therapies Dresden (CRTD) of TUD Dresden University of Technology is an academic home for scientists from more than 30 nations. Their mission is to discover the principles of cell and tissue regeneration and leverage this for the recognition, treatment, and reversal of diseases. The CRTD links the bench to the clinic, scientists to clinicians to pool expertise in stem cells, developmental biology, gene-editing, and regeneration towards innovative therapies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease, hematological diseases such as leukemia, metabolic diseases such as diabetes, bone and retina diseases.
The CRTD was founded in 2006 as a research center of the German Research Foundation (DFG) and funded until 2018 as a DFG Research Center, as well as a Cluster of Excellence. Since 2019, the CRTD is funded by the TU Dresden and the Free State of Saxony.
The CRTD is one of three institutes of the central scientific facility Center for Molecular and Cellular Bioengineering (CMCB) of the TU Dresden.
http://www.tud.de/crtd
http://www.tud/de/cmcb

About Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has more than 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en  

About TUM
The Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 600 professors, 50,000 students, and 11,000 academic and non-academic staff. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with the TUM Asia campus in Singapore as well as offices in Beijing, Brussels, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006, 2012, and 2019 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. https://www.tum.de/en/

Original Publication
Marija Lugar, Anne Eugster, Peter Achenbach, Thekla von dem Berge, Reinhard Berner, Rachel E.J. Besser, Kristina Casteels, Helena Elding Larsson, Gita Gemulla, Olga Kordonouri, Annett Lindner, Markus Lundgren, Denise Müller, Mariusz Oltarzewski, Anne Rochtus , Marlon Scholz, Agnieszka Szypowska, John A. Todd, Anette-Gabriele Ziegler, Ezio Bonifacio for the GPPAD Study Group: SARS-CoV-2 infection and the development of islet autoimmunity in early childhood. JAMA (2023)
Link: https://doi.org/10.1001/jama.2023.16348

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