Autoantibodies Herald the Onset of Type 1 Diabetes

The onset age of type 1 diabetes in children can now be accurately estimated for the first time. In the largest international study of its kind, scientists of Helmholtz Zentrum München, a partner in the DZD, found that young people develop type 1 diabetes within a maximum of 20 years after the first appearance of so-called multiple autoantibodies in the blood. Onset within this timeframe, whether earlier or later, depends on individual characteristics and conditions. “Our findings allow us to make the diagnosis of type 1 diabetes before the disease is clinically manifested,” said Professor Anette-Gabriele Ziegler, a member of the board of the German Diabetes Association (DDG) and director of the Institute of Diabetes Research of Helmholtz Zentrum München. Early detection also offers opportunities for improved and preventive treatments.


Type 1 diabetes is an autoimmune disease, the onset of which is usually in childhood or adolescence. The body’s own defense system destroys cells in the pancreas that secrete the blood glucose-lowering hormone insulin. As a result, the body can no longer regulate blood glucose levels, and the affected individuals are dependent on insulin injections throughout their entire lives. Indicators of this looming attack on the pancreas are antibodies that form in the blood. “These autoantibodies often develop many years before the onset of diabetes and are thus a pre-indication of the disease,” said Ziegler “Some children have various autoantibodies in their blood as early as age three.” In the “BABYDIAB” and “BABYDIET” studies, the institute director monitors children of diabetics from birth on who are at increased risk of developing diabetes.

Data from a 20-year period
Her most recent study has now been published in the Journal of the American Medical Association (JAMA). Ziegler and her co-authors pooled their studies with two similar studies from Finland and the U.S. and thus compared the data of a total of 13,777 children over a period of 20 years. More than 1000 children developed autoantibodies. In 585 children, more than one type of autoantibody could be detected. Of these children, 70 percent developed type 1 diabetes in the following ten years. “After 15 years, 85 percent of the children had developed type 1 diabetes, at the end of the observation period close to 100 percent,” Ziegler said. Children without autoantibodies almost never developed type 1 diabetes – for them the ten-year risk was 0.4 percent.

Predictable onset
“The study shows that the onset of diabetes is often predictable,” said Dr. Erhard Siegel, president of the German Diabetes Association (DDG). The detection of antibodies offers an opportunity for early diagnosis of type 1 diabetes. The diagnosis of pre-diabetes could also result in new targets for therapy, according to Siegel. “We now know that islet cells are not destroyed in a day.” The enemy attack of the immune system may take place over a period of a few weeks up to decades. “During this time there might be a chance of preserving the body’s own insulin production – at least in part – and of controlling the excessive immune reaction,” added Professor Ezio Bonifacio of the Research Center for Regenerative Therapies at the Technical University of Dresden, which is involved in the study.
Treatments with antigen-based immunotherapy are currently being tested in children and young adults with autoantibodies. “Diabetes is a very common, widespread disease and is therefore a focus of our research activities,” said Professor Günther Wess, scientific director of Helmholtz Zentrum München. “By pooling results from international studies on this topic, we will gain deeper insight into the underlying mechanisms of the disease, which will contribute to our progress toward personalized medicine.

Objective: treatment at preclinical stage
Screening for autoantibodies in children would make good sense, according to Ziegler: “If by means of screening we could identify the antibody carriers, severe metabolic disturbances could be prevented already today. “Based on the new findings, type 1 diabetes could in the future be divided into disease stages and could already be treated in the preclinical stage,” Ziegler said. “We now know when the clock of the disease starts ticking and that there is no way back – unless we intervene with an effective preventive approach.”


Original publication:
Anette-G. Ziegler, Marian Rewers, Olli Simell, Tuula Simell, Johanna Lempainen, Andrea Steck, Christiane Winkler, Jorma Ilonen, Riitta Veijola, Mikael Knip, Ezio Bonifacio, George-S. Eisenbarth
Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children; JAMA, 2013;309(23):2473-2479