Time to include standard care screenings for diagnosis of pre-symptomatic type 1 diabetes

Researchers at Helmholtz Zentrum München employed the world's first early detection test for type 1 diabetes in a large-scale population study in Bavaria, Germany, and investigated its effects. For the first time, screening for islet autoantibodies makes it possible to diagnose pre-symptomatic stages of type 1 diabetes. The study based on 90,632 screened children suggests that these screenings can reduce the progression from pre-symptomatic type 1 diabetes to life-threatening diabetic ketoacidosis. It provides the basis for drafting new guidelines for future diagnosis and for discussing a recommendation towards the inclusion of screenings in standard care services.

© Helmholtz Zentrum München

Type 1 diabetes is the most common metabolic disease in children and adolescents with sometimes life-threatening complications. “Our goal is a world without type 1 diabetes”, says Prof. Anette-Gabriele Ziegler, Director of the Institute of Diabetes Research at Helmholtz Zentrum München. The scientist and physician hopes to prevent the disease in its pre-symptomatic stage with an immunomodulating therapy. “In order to be able to treat type 1 diabetes at an early stage, we have to detect the disease as early as possible. To do so, we need appropriate diagnostics for children,” explains Ziegler.

Partnering with pediatric healthcare

Ziegler and her team initiated “Fr1da”: In this four-year (2015-2019) study, 90,632 Bavarian children between the age of 2 and 5 years were screened for islet autoantibodies. 682 pediatricians in Bavaria participated in the screenings by implementing a Fr1da blood test into their routine well-baby exams.

Diagnosis based on islet autoantibodies

Children were diagnosed with pre-symptomatic type 1 diabetes if two or more islet autoantibodies were found. The presence of these antibodies indicates that the body’s immune system is attacking the insulin-producing pancreatic beta cells, which is the cause of type 1 diabetes. These antibodies can be detected in the blood even years before the first disease symptoms appear. In a novel approach, children with islet autoantibodies were categorized into three stages: stage 1 (normoglycemia) and 2 (dysglycemia) or 3 (clinical) type 1 diabetes, allowing personalized monitoring and follow-up care.

Preventing diabetic ketoacidosis

The screening of 90,632 Bavarian children revealed pre-symptomatic type 1 diabetes for 280 of them (0.31 %). Out of these 280 children, 24.9 % developed clinical type 1 diabetes (stage 3). Only two of these progressed to diabetic ketoacidosis.

Ziegler comments:

A potential clinical benefit of identifying type 1 diabetes in a pre-symptomatic stage is a reduction in the prevalence of life-threatening diabetic ketoacidosis”.

In this study, the prevalence of diabetic ketoacidosis was less than 5 %. In unscreened children however, the prevalence of diabetic ketoacidosis is 20% in Germany, and 40% in the United States. This suggests the high potential of screenings to reduce disease severity internationally.

Melanie Huml, Bavaria's Minister of Health and patron of Fr1da:

The Fr1da study, sponsored by the Bavarian Ministry of Health, is an important contribution to the early diagnosis of diabetes mellitus type 1. The high number of children tested and the participating pediatricians in Bavaria is a great success. I hope that the results will help to accompany and support affected children and their parents in the best possible way. After all, timely treatment makes it possible to prevent the development of serious comorbidities of diabetes mellitus such as cardiovascular or kidney diseases. My aim is to make parents more aware of diabetes mellitus in children. Across Bavaria, around 4,500 children, adolescents and young adults under the age of 20 are affected by type 1 diabetes. Currently, there is no cure for this disease, which requires further intensive research. For this reason, I was happy to take on the patronage of the Fr1da study”.

Novel guidelines for standard care

“In today’s rapidly changing environment, Helmholtz Zentrum München is committed to cutting edge research that delivers innovative solutions for a healthier society. This study represents a perfect example how with this strategy many years of our scientists’ hard work can benefit patients around the globe”, says Prof. Matthias Tschöp, CEO of Helmholtz Zentrum München.

In a next step, the researchers will perform a cost-benefit analysis of the screenings. This could further support the inclusion of screenings for pre-symptomatic type 1 diabetes into the standard care service catalogue of the public health insurance funds. “Early diagnosis would make the road to a world without type 1 diabetes much easier,” Ziegler said. Together with an international team, she is working intensively on developing an effective therapy to prevent the onset of type 1 diabetes. Early diagnosis is an important requirement for this major goal.

Strong funding for pioneering study

The Fr1da study is conducted by Helmholtz Zentrum München, the Professional Pediatric Association of Bavaria (BVKJ e.V.) and PaedNetz Bayern e. V. It is under the patronage of the Health Minister of Bavaria, Melanie Huml, and has attracted strong international interest. It received funding from JDRF, the LifeScience-Stiftung, the Leona M. and Harry B. Helmsley Charitable Trust, the Bavarian Ministry of Health and Care, Deutsche Diabetes Stiftung, BKK Landesverband Bayern, B. Braun-Stiftung, Deutsche Diabetes-Hilfe, and the German Center for Diabetes Research (DZD). Screenings have since been extended to Lower Saxony (Fr1dolin study) and have become a model for numerous other initiatives worldwide.