Researchers develop improved method for calculating type 1 diabetes risk
An international research group headed by scientists from Helmholtz Zentrum München has developed a method for calculating the risk for developing type 1 diabetes that is significantly superior to earlier methods. By analyzing up to 41 gene sites, it is possible to identify children at birth who are at least 25-times more likely to develop type 1 diabetes. The test is already being used in a type 1 diabetes prevention project across Europe. The work, published in 'PLOS Medicine', could also serve as a model for other diseases that are associated with multiple genes.
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 Zentrum München 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."
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