Study supports routine childhood screening for type 1 diabetes

The Fr1da study, coordinated by Helmholtz Munich, has been investigating for ten years whether the early stages of type 1 diabetes can be detected in children in routine pediatric care. The latest evaluation shows that the screening program is sustainably viable and identifies the majority of children who will later develop stage 3 (clinical) type 1 diabetes.

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, children may develop diabetic ketoacidosis, a serious medical emergency. So-called islet autoantibodies can be detected in the blood years before the disease develops. If identified this early stage, families can be prepared, children can receive medical follow-up, and serious metabolic complications can be avoided. Researchers at Helmholtz Munich are now publishing their latest assessment 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 the early stages of type 1 diabetes – not in specialized centres, but through regular pediatric care. A total of 716 pediatricians in private practice participated. Fr1da therefore provides one of the most comprehensive evidence to date that screening for early-stage type 1 diabetes can be permanently implemented into routine pediatric practice.

For screening, a small blood sample is taken at the participating pediatric practice and analyzed in the laboratory for islet autoantibodies. Researchers define the early stage as the confirmed presence of at least two different islet autoantibodies in two consecutive blood samples. In stage 1, blood sugar 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.

In the first screening, 590 children were found to have early-stage type 1 diabetes – about 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 children who develop clinical type 1 diabetes. After five years, the chance of progressing from the initial stage to clinical type 1 diabetes was 36.2 percent. Research has shown that while children with stage 1 diabetes have a higher risk of developing stage 3 type 1 diabetes, the majority of children who develop stage 3 type 1 diabetes have no family history of the disease. Therefore, screening should not be limited to children who have a family history of type 1 diabetes. Additionally, once early-stage diagnosis was made, researchers found no difference in disease progression between children with and without a family history.

“These data show that screening in the general population is justified,” says Dr. Christian Winkler, who leads the Fr1da team at Helmholtz Munich and 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 similar rates in different stages. Among children who had stage 1 or stage 2 disease, progression to advanced stages was about 20 percent each year. “This is the first real evidence that shows that the disease process in the pancreas is triggered by autoimmunity and potentially changes our approach to the timing of treatment.” Says Professor Annette-Gabrielle Ziegler, director of the Diabetes Research Institute at Helmholtz Munich and principal investigator of the study.

The second screening also proved important. Children were initially examined at an average age of 3 years. In more than 11,700 children whose initial test was negative, testing was repeated about 3 years later. It identified an additional 29 children with early-stage type 1 diabetes. Therefore, new early-stage cases were identified in re-screening almost as frequently as in the first screening. “Some children develop islet autoantibodies a little later in childhood,” says Winkler. “That’s why we recommend a second test after a few years.”

Diabetes screening is possible for all children

For families, a positive screening result does not mean the child already has diabetes symptoms or needs insulin immediately. Families receive information, education and access to specialized diabetes centers. There, the oral glucose tolerance test is used to assess how stable the child’s metabolism still is. Then there are regular follow-up examinations. The goal is to detect infection early in stage 3 type 1 diabetes and prevent diabetic ketoacidosis whenever possible.

The Fr1da study has been helpful in investigating general population type 1 diabetes screening. At Helmsley, we support Fr1da because early detection of type 1 diabetes improves long-term health outcomes.”

Anne Korlova, Program Officer at Helmsley Charitable Trust

Fr1da data are also relevant for new prevention strategies. Disease-modifying treatments – treatments that can affect the course of the disease and delay the onset of stage 3 type 1 diabetes – are needed for early diagnosis. Additionally, the data shows 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 means not only that screening can be implemented in the general population, but that therapies that are effective in one group will also be effective in another,” says Ziegler. “Our goal is to provide such screening to all children in the future, not just those in individual risk groups”.

“The ability to detect type 1 diabetes early through screening and monitoring is a significant breakthrough, with enormous potential to reach broader populations and change the course of the disease for those who will develop it. It is a cornerstone of Breakthrough T1D’s efforts to accelerate the cure for type 1 diabetes,” said Ph.D. said Esther Latres. Senior Vice President of Research at Breakthrough T1D. “The Fr1da study has advanced our understanding of disease progression in children and demonstrated the value and practicality of early detection as part of routine clinical care, advancing clinical trials and enabling access to emerging disease-modifying treatments.”