Type 1 diabetes usually begins long before children develop typical symptoms such as excessive thirst, weight loss, or fatigue. Often, families are unaware of these signs. If the disease is detected too late, the children can develop diabetic ketoacidosis, a severe medical emergency. So-called islet autoantibodies can be detected in the blood years before the disease develops. If this early stage is identified, families can be prepared, children can receive medical follow-up, and severe metabolic complications can be avoided. Researchers at Helmholtz Munich are now publishing their latest evaluation of the Fr1da study in the journal JAMA. Since Fr1da was launched in February 2015, more than 220,000 children in Bavaria have been tested for early stages of type 1 diabetes – not in specialized centers, but through routine pediatric care. A total of 716 pediatricians in private practice participated. Fr1da therefore provides one of the most comprehensive pieces of evidence to date that screening for early-stage type 1 diabetes can be implemented sustainably in general pediatric practice.
For the screening, a small blood sample is taken at participating pediatric practices and analyzed in the laboratory for islet autoantibodies. The researchers define an early stage as the confirmed presence of at least two different islet autoantibodies in two consecutive blood samples. In stage 1, blood glucose levels are still normal; in stage 2, the first signs of impaired glucose metabolism appear. Only stage 3 corresponds to clinical type 1 diabetes where insulin is required.
Most Children With Early-Stage Type 1 Diabetes Do Not Have a Family History of the Disease
At the first screening, 590 children were found to have early-stage type 1 diabetes – corresponding to around 0.3 percent of the children screened. During follow-up, 212 of these children progressed to stage 3 type 1 diabetes. This represents 81 percent of the children who went on to develop clinical type 1 diabetes. After five years, the probability of progressing from an early stage to clinical type 1 diabetes was 36.2 percent. The research showed that while children with a first-degree relative with type 1 diabetes have a higher risk of developing type 1 diabetes, most of the children who develop stage 3 type 1 diabetes have no family history of the disease. Therefore, screening should not be limited to children with a family history of type 1 diabetes. Additionally, once an early stage has been diagnosed, the researchers observed no differences in disease progression in children with and without a family history.
“These data show that screening in the general population makes sense,” says Dr. Christiane Winkler, who leads the Fr1da team at Helmholtz Munich and is first author of the study. “If we only test children with a family history of type 1 diabetes, we miss the majority of children who later develop stage 3 type 1 diabetes.”
A new finding is that the disease progresses at a similar rate across stages. The progression to advanced stages was around 20 percent every year in children who had stage 1 or stage 2 disease.
“This is the first real evidence indicating that the disease process in the pancreas is happening from the outset of autoimmunity and potentially transforms our approach to the timing of therapies.” says Prof. Anette-Gabriele Ziegler, Director of the Institute of Diabetes Research at Helmholtz Munich and principal investigator of the study.
A second screening also proved important. Children were initially screened at an average age of 3 years. In more than 11,700 children who initially tested negative, the test was repeated around 3 years later. This identified 29 additional children with early-stage type 1 diabetes. Hence, rescreening identified new early-stage cases almost as frequently as at first screening.
“Some children develop islet autoantibodies a little later in childhood,” says Winkler. “That is why we recommend a second test after a few years.”
Diabetes Screening Is Feasible for All Children
For families, a positive screening result does not mean that the child already has diabetes symptoms or needs insulin immediately. Families receive information, education, and access to specialized diabetes centers. There, an oral glucose tolerance test is used to assess how stable the child’s metabolism still is. Regular follow-up examinations then take place. The goal is to detect the transition to stage 3 type 1 diabetes early and to prevent diabetic ketoacidosis whenever possible.
“The Fr1da study has been instrumental in investigating general population type 1 diabetes screening,” says Anne Koralova, Program Officer at the Helmsley Charitable Trust. “At Helmsley, we support Fr1da because identifying type 1 diabetes early improves long-term health outcomes.”
The Fr1da data are also relevant for new prevention strategies. Disease-modifying therapies – treatments that can influence the course of the disease and delay the onset of stage 3 type 1 diabetes – require an early diagnosis. At the same time, the data show how quickly children progress from one stage to the next, providing an important basis for future studies. In the long term, Fr1da aims to help bring early detection into routine care.
“The study shows that the disease process is the same in children with and without a family history of type 1 diabetes. This not only means that screening is implementable in the general population, but that therapies shown to be effective in one group will be effective in the other,” says Ziegler. “Our goal is for such screening to be offered to all children in the future, not only to individual risk groups”.
“The ability to detect type 1 diabetes early through screening and monitoring is a significant breakthrough with vast potential to reach a broad population and change the course of the disease for those who will develop it. It is a cornerstone of Breakthrough T1D’s efforts to accelerate cures for type 1 diabetes,” said Esther Latres, Ph.D. Senior Vice President of Research at Breakthrough T1D. “The Fr1da study has advanced our understanding of disease progression in children and demonstrates the value and practicality of early detection as part of routine clinical care, advancing clinical trials, and enabling access to emerging disease-modifying therapies.”
Original Publication
Funding
The Fr1da study was supported by Breakthrough T1D, LifeScience Stiftung, the Leona M. an Harry B. Helmsley Charitable Trust, the Deutsche Diabetiker Bund e.V., the Bavarian Ministry of Economic Affairs, Energy, and Technology, the EASD-Novo Nordisk Foundation Diabetes Prize for Excellence and the German Center for Diabetes Research (DZD e. V.).
