Improved assessment of the genetic risk of type 1 diabetes

Using a new genetic risk score, scientists hope to test more than 300,000 babies for their type 1 diabetes risk in the coming years. © Helmholtz Munich

Type 1 diabetes is the most common metabolic disease of childhood and adolescence. It is caused by a misguided immune response that is present long before symptoms appear and destroys the insulin-producing cells in the pancreas. Early and reliable assessment of the disease risk is needed to prevent this immune process. Until now, scientists have identified children with increased risk by focussing on two genes of the HLA (human leukocyte antigen) system, a group of genes that are crucial for the function of the immune system, or by selecting children with a family history of the disease. Neither method, however, is adequate: 90 percent of all affected children do not have a first degree relative with type 1 diabetes, and although selection via the HLA genes can identify children that have over 10-fold risk as compared to the background risk of 0.4 percent , it is at best around 5 percent in children with the highest risk genotypes.

In a prospective study, a team of researchers headed by Professor Ezio Bonifacio of the DFG Center for Regenerative Therapies in Dresden, Dr. Andreas Beyerlein and Professor Anette-Gabriele Ziegler (both at Helmholtz Munich and Klinikum rechts der Isar of the Technical University of Munich, and the Diabetes Study Group (Forschergruppe Diabetes e.V.)), together with colleagues from the UK, Sweden, Finland, Canada and the United States, determined risk scores derived from 41 gene loci associated with type 1 diabetes risk. They used data from more than 3,000 children in the TEDDY study* who have no relatives with type 1 diabetes. “With these risk scores, we can identify children who have a more than a ten percent risk of developing presymptomatic type 1 diabetes by their sixth birthday,” Ezio Bonifacio explains. “That means an at least 25-fold increased risk compared to the population average. The process is therefore significantly superior to previous methods.”

The test is already being used in a major clinical study on the prevention of type 1 diabetes. As part of the Freder1k study, parents in Bavaria, Lower Saxony and Saxony can have their baby tested for type 1 diabetes risk at the maternity hospital or during one of the early paediatrician visits free of charge. Hospitals and research institutes in Sweden, the UK, Poland and Belgium are also taking part. In total, the scientists hope to test more than 300,000 babies in the coming years. Children found to be at risk can be enrolled in a trial that aims to prevent the development of type 1 diabetes. “It is largely thanks to the improved analytical method that it was possible to launch such a large-scale prevention project,” says Anette-Gabriele Ziegler. “We hope that this model can also be applied to other childhood autoimmune diseases in future.”

Further Information

*TEDDY (The Environmental Determinants of Diabetes in the Young) investigates factors that contribute to the development of type 1 diabetes. Scientists working in six clinical research centers in the USA, Finland, Sweden and Germany are following over 8,000 children with risk genes for type 1 diabetes from birth to the age of 15. TEDDY is funded by the National Institutes of Health, the Centers for Disease Control and Prevention and the Juvenile Diabetes Research Foundation.

Original Publication:
Bonifacio E. et al. (2018): Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: A prospective study in children. PLoS Medicine, DOI: 10.1371/journal.pmed.1002548

As German Research Center for Environmental Health, Helmholtz Munich pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Munich has about 2,500 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Munich is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Diabetes Research (IDF) focuses on the understanding of the natural history of type 1 diabetes, on the identification of mechanisms and predictive markers of the disease, and the translation of findings into trials to prevent type 1 diabetes in man. In particular, the institute’s aim is to develop an immune tolerance using antigen-based therapy. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world’s first prospective birth cohort study, identified the first two years of life as being most susceptible for the initiation of type 1 diabetes associated autoimmunity. The Fr1da study is the first population-based approach for the early diagnosis type 1 diabetes associated autoimmunity in childhood. The IDF is part of the Helmholtz Diabetes Center (HDC).

Founded in 2006, the DFG Research Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence at the TU Dresden aims to explore the human body's regenerative potential and to develop regenerative therapies for hitherto incurable diseases. Key disease areas of research include haematology and immunology, diabetes, neurodegenerative diseases, and bone regeneration. The CRTD is part of the Center for Molecular and Cellular Bioengineering (CMCB), a central institute of the Technische Universität Dresden.