New knowledge about type 1 diabetes – the large-scale TEDDY study will soon be completed

"New knowledge about type 1 diabetes – the large-scale TEDDY study will soon be completed"
Link to interview with senior professor of experimental diabetes at Lund University and principal investigator of the TEDDY study in Sweden (YouTube)

Sweden and Finland are the two top countries for incidence rates of type 1 diabetes in children in the world. Today, more than 1.2 million children and adolescents under the age of 20 have type 1 diabetes. The incidence of the disease is also increasing worldwide. People with type 1 diabetes require treatment with insulin to survive and it is important to understand the causes of type 1 diabetes to prevent or delay the disease progression.

The TEDDY study began in 2004 and includes almost 8,700 children from Sweden, Finland, Germany and the United States. The research project is funded by the U.S. National Institutes of Health (NIH) and aims to ascertain what causes children to develop type 1 diabetes.

The study, which has led to the publication of many peer-reviewed studies in high-impact journals, provides additional evidence for the theory that a combination of genetic and environmental factors affects whether a person develops the disease.

The most important lessons from the study are presented in Nature Reviews Endocrinology, ahead of the final collection of data and samples in March 2025. Åke Lernmark, principal investigator of the TEDDY study in Sweden, has led work on the article. Jeffrey Krischer, director of the TEDDY Data Coordinating Center and co-chair of the international TEDDY study, is one of the leading co-authors.

"The study’s success is due to the commitment and sacrifice on the part of the participating children and their families. Most were reassured by the close relationships with study coordinators and the careful monitoring of diabetes risk provided by the study. Many of the participating families wanted to help us understand the causes of the disease," says Jeffrey Krischer, professor and director of the Health Informatics Institute at the University of South Florida.

Screening for type 1 diabetes

In the study, the researchers have followed the development of diabetes-related autoantibodies in children. A blood sample showing the presence of one of four diabetes-related autoantibodies suggests that cells in the pancreas that produce insulin are attacked by the body's own immune system. The TEDDY study has shown, among other things, that autoantibodies formed against insulin are most common during the child's first three years. The discovery of genetic risk factors has enabled the researchers to estimate an individual's risk of developing the disease.

"Some of us believed that the disease would be diagnosed shortly after the first autoantibody against insulin was formed, but our studies have shown that it can take several years before the child develops the disease. Interest in screening for type 1 diabetes within the healthcare system is increasing in many countries, and our genetic risk scores can be used to identify which children may benefit most from being screened for the disease," says Åke Lernmark, senior professor of experimental diabetes at Lund University Diabetes Centre and a member of the study's steering committee.

Continued research

The researchers have also found a connection between enterovirus infection, the development of diabetes-related autoantibodies and type 1 diabetes. Another important finding is that administering probiotics to infants at increased risk of developing the disease can reduce the risk of them developing diabetes-related autoantibodies.

Results from the TEDDY study have contributed to the development of several new research projects that are currently underway at Lund University Diabetes Centre. Researchers are, for example, trying to prevent type 1 diabetes by administering probiotics and vaccinating against Covid-19.

The TEDDY study has also increased knowledge about celiac disease and thyroiditis, two other autoimmune diseases. This knowledge is being used in the TRIAD study, which screens children in southern Sweden for the three diseases type 1 diabetes, celiac disease and thyroiditis.

"It is incredible to see that results from the TEDDY study have led to new studies. Even if we stop collecting samples from the children, analysis of the data continues. An important question that remains to be answered is what role viral infections play in the development of the disease. If we get a firm answer to this question, we can find new ways to stop the disease," says Åke Lernmark.

Facts the TEDDY study: The TEDDY study began in 2004 and includes almost 8,700 children from Sweden, Finland, Germany and the United States. The research project aims to ascertain what causes children to develop type 1 diabetes. The children submitted their first samples when they were four months old and are followed up to the age of 15. The researchers have collected many different types of samples from the children, including measurements of physical activity, blood samples, nasal samples, urine and stool samples, as well as samples of teeth and water intake. The participants have also been interviewed about diet and other life experiences. The TEDDY study will complete the collection of data in March 2025. Analyses of the data are expected to continue until 2035.
Link to TEDDY study's international website
Link to The TEDDY study's Swedish website

Autoantibodies: An autoantibody is an antibody produced by the body that targets the body’s own tissue, often resulting in tissue damage.  Diabetes-related autoantibodies are used to identify those at risk of developing type 1 diabetes. The diabetes-related autoantibodies are IAA, GADA, IA-2A and ZnT8A. Individuals with two, three or four autoantibodies have an increased risk of developing the disease. A diagnosis can only be made when a person shows symptoms.
The TEDDY study has also followed the development of the autoantibody tTGA, associated with celiac disease, and the autoantibody TPOA, associated with thyroiditis.

Publication
"Looking back at the TEDDY study: lessons and future directions"
Nature Reviews Endocrinology, 04 Nov, 2024
Research reported in this press release is supported by the U.S. National Institutes of Health under award numbers DK063829, DK063861, DK063821, DK063865, DK063863, DK063836, DK063790, DK095300, DK100238, DK106955, DK112243, DK117483, DK124166 and DK128847.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.