Massive Eight-Country Trial Shows Childhood Type 1 Diabetes Screening Works Across Europe

A sweeping European screening initiative has demonstrated that large-scale detection of early-stage type 1 diabetes in children is feasible across vastly different healthcare systems, according to new findings presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, held from September 28 to October 2. The EDENT1FI consortium, a collaborative initiative coordinated jointly by Professor Chantal Mathieu of KU Leuven in Belgium and Professor Anette-Gabriele Ziegler of Helmholtz Munich in Germany, screened more than 140,000 children and adolescents in eight countries using a single harmonised protocol, providing the strongest evidence yet that population-based screening for presymptomatic type 1 diabetes can be rolled out continent-wide.

The scientific rationale behind the programme rests on a conceptual shift in how type 1 diabetes is understood. Earlier work by members of the consortium, including Dr Peter Achenbach and Professor Anette-Gabriele Ziegler of the Institute of Diabetes Research at Helmholtz Munich, established that the disease progresses through distinct presymptomatic stages before clinical onset. What was traditionally recognised as symptomatic diabetes is now classified as stage 3, while stages 1 and 2 describe earlier phases in which the immune system has already begun attacking the insulin-producing beta cells of the pancreas but blood glucose remains normal or only subtly abnormal. Identifying children during these presymptomatic windows matters because preventive and disease-modifying therapies are now becoming available. One such therapy, teplizumab, has already been approved to delay progression, and others are in development. Early detection also carries an immediate clinical benefit: children whose condition is known before symptoms appear face a substantially reduced risk of presenting with diabetic ketoacidosis, a life-threatening metabolic emergency that often marks the first diagnosis of type 1 diabetes.

The EDENT1FI consortium was designed to advance population-based screening and to harmonise early detection approaches across national borders. Using a common protocol, participating centres set out to assess the feasibility of screening for islet autoantibodies, to measure participation rates, to determine the prevalence of early-stage type 1 diabetes in the general child population, and to evaluate the performance and comparability of laboratory assays across different countries. Screening sites operated in the Czech Republic in Prague; in Denmark and Sweden in the Copenhagen and Öresund Region; in Germany in Munich, Hanover and Dresden; in Italy in Milan; in Poland in Warsaw and Katowice; in Portugal in Lisbon, Matosinhos and Beja; and in the United Kingdom in Birmingham.

The technical workflow followed a tiered design intended to balance sensitivity with practicality. Initial testing relied on capillary blood samples, collected as dried blood spots in the United Kingdom, and used a combined assay for three autoantibodies: GADA, directed against glutamic acid decarboxylase; IA-2A, directed against insulinoma-associated antigen-2; and ZnT8A, directed against zinc transporter 8. Samples that tested positive were then analysed for four autoantibodies, adding IAA, insulin autoantibodies, at two central laboratories in Munich and Milan. Participants with at least two confirmed autoantibodies underwent further confirmatory testing, and a diagnosis of early-stage type 1 diabetes was made only after this confirmation. Individuals diagnosed with early-stage disease were invited to receive education about their condition and to undergo metabolic staging through oral glucose tolerance testing and measurement of HbA1c, which distinguishes stage 1 disease, where glucose metabolism remains normal, from stage 2, where dysglycaemia has emerged, and from stage 3, where clinical symptoms develop.

Crucially, the screening targeted children from the general population, not only those with a known family history of the disease. Children and adolescents aged 2 to 10 years were eligible in Germany, while other countries screened those aged 2 to 17 years owing to site-specific variations in screening protocols. This general-population emphasis is scientifically important because the vast majority of children who develop type 1 diabetes have no first-degree relative with the condition, meaning that family-history-based risk stratification alone would miss most future cases.

In total, 140,568 young people, 49.2 percent of them female, took part in screening, with a median age of 7.6 years. Of these, 10,273 children, or 7.3 percent, had a first-degree family history of type 1 diabetes, while 127,754, or 90.9 percent, had no such relative, and family history was not reported for 2,541 participants. Among children with a first-degree relative with the disease, 219 were found to have early-stage type 1 diabetes, equivalent to 2.13 percent or roughly one in 45. Among children without a family history, 408 cases were detected, or 0.32 percent, approximately one in 350. These figures confirm that although genetic risk is elevated in relatives, the sheer size of the general population means that most presymptomatic cases are found among children with no family connection to the disease.

Country-level results revealed meaningful variation in prevalence. Among children without a first-degree relative with type 1 diabetes, frequencies ranged from 0.22 percent in Germany to 0.42 percent in the United Kingdom and 0.47 percent in Sweden. Prevalence was also associated with age: it was lowest, at 0.22 percent, among children younger than 4 years, rising to 0.31 percent in the 4 to under 8 age group and 0.40 percent among those aged 8 to under 13. In Italy, where screening took place in the EASD host city of Milan, 4,507 participants with a median age of 6.5 years were screened, including 3,641, or 80.8 percent, without a first-degree family history, of whom five, or 0.14 percent, had early-stage type 1 diabetes. No cases were detected among the 167 Italian children who did have a first-degree relative with the condition.

The larger national cohorts provided further detail. In the United Kingdom, 17,409 children with a median age of 8.4 years were screened; 59 cases, or 0.42 percent, were found among those without a first-degree relative with type 1 diabetes, and 67 cases, or 3.43 percent, among those with one. In Sweden, 7,926 children with a median age of 9.4 years were screened, yielding 36 cases, or 0.47 percent, among those without a family history and 4 cases, or 1.21 percent, among those with one. In Germany, where 43,470 children with a median age of 4.3 years were screened, case rates were notably lower, at 90 cases, or 0.22 percent, in children without a first-degree relative and 35 cases, or 1.36 percent, in those with one. The lower German figures may partly reflect the younger age distribution of the German cohort, given the observed rise in prevalence with age.

Of the 634 participants diagnosed with early-stage type 1 diabetes across the consortium, 386, or 61 percent, completed metabolic staging. The results showed that 300, or 78 percent, had stage 1 disease, 70, or 18 percent, had stage 2, and 16, or 4.1 percent, had already reached stage 3. This distribution underscores the value of antibody screening: the overwhelming majority of detected cases were identified at the earliest presymptomatic stage, when intervention opportunities are greatest. All participants identified with early-stage type 1 diabetes have been included in the European pre-T1D Registry, creating a harmonised continental cohort that can support future studies of disease progression and prevention.

The authors conclude that screening principles originally developed in Germany can be successfully applied to regions with different healthcare systems, and that the EDENT1FI initiative demonstrates that screening for early-stage type 1 diabetes can be effectively implemented throughout Europe. The next steps, they say, are aimed at integrating screening for early-stage type 1 diabetes in the general population into standard medical care. Similar screening initiatives are under way worldwide, including in the United States and Australia. Policy momentum is already visible within Europe: Italy has introduced legislation to establish nationwide screening for type 1 diabetes, although the government and regional health systems are still working to implement the law. The consortium recommends that screening be rolled out across Europe with three testing windows, at ages 2 to 4 years, 6 to 8 years and 10 to 15 years, an approach designed to capture the rising prevalence observed across childhood age groups while embedding early detection into routine paediatric care.

Subject of Research: Population-based screening of children for presymptomatic type 1 diabetes using islet autoantibody testing across eight European countries

Article Title: Study across eight European countries shows that screening for type 1 diabetes can be effectively implemented in children across Europe (EDENT1FI)

Article References: Study across eight European countries shows that screening for type 1 diabetes can be effectively implemented in children across Europe (EDENT1FI). (n.d.). Original publication

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Keywords: type 1 diabetes, EDENT1FI, islet autoantibodies, screening, EASD, presymptomatic stage, teplizumab, pediatrics, Europe, autoimmunity, diabetic ketoacidosis, public health