Screening for Islet Autoantibodies in Childhood: Insights from the Fr1da Study on Early-Stage Type 1 Diabetes Prevalence and Progression

Background: Type 1 diabetes (T1D) can be detected presymptomatically by testing for islet autoantibodies and classified into stage 1 (multiple islet autoantibodies, normoglycemia), stage 2 (dysglycemia) and stage 3 (hyperglycemia, clinical onset of T1D). From 2015 to 2024, the Fr1da study screened children aged 2-10 years from the general population in Bavaria to diagnose early-stage T1D by detecting at least two confirmed positive islet autoantibodies, followed by education and metabolic staging and monitoring until stage 3 T1D.

Objective: To assess the prevalence of early-stage T1D and progression to clinical T1D.

Methods: Children were screened for islet autoantibodies (GADA, IA-2A, ZnT8A, IAA) in a two-step procedure: initial testing with ELISA and LIPS assay (>98th percentile) followed by confirmatory testing with radio-binding assays. Multiple islet autoantibody-positive children were staged by OGTT and/or HbA1c values. It was recommended that islet autoantibody-negative children should be retested after 3 to 4 years and that those who tested positive for single islet autoantibodies at a high cut-off value should be tested annually for 3 years.

Results: Of 203,354 children enrolled in the Fr1da study, 202,822 had sufficient blood samples for screening. Early-stage T1D was diagnosed in 569 (0.28%) children, including 29 who developed clinical T1D before confirmatory testing. Of 202,137 children without early-stage T1D, 111 were single islet autoantibody-positive. 10,231 children who were not diagnosed with early-stage T1D in the first screening took part in a second screening for islet autoantibodies (rescreen). Here, multiple islet autoantibodies were found in 22 children and single islet autoantibodies in 9 children. In addition, 14 of the 120 single islet autoantibody-positive children developed multiple islet autoantibodies on follow-up, increasing the total number of children diagnosed with early-stage T1D to 605 (0.3%). Of those diagnosed with early-stage T1D, 476 participated in the education and metabolic staging, and 374 (78.6%) had stage 1, 82 (17.2%) stage 2 and 20 (4.2%) stage 3 T1D. A further 149 children progressed from stage 1 or 2 to stage 3 T1D within a median follow-up of 2.9 years (IQR 1.1-5.3). Of these 169 children, 7 (4.1%) presented with diabetic ketoacidosis (DKA) at clinical onset. Staging was pending or refused in 100 children, of whom 17 developed stage 3 T1D within a median of 1.3 years (0.7-3.0), with 2 (11.8%) cases of DKA. Of the single islet autoantibody-positive children, 4 developed stage 3 T1D after a median of 1.9 years (0.4-4.7), and none had DKA.

Conclusion: Screening for islet autoantibodies identifies children at early-stage T1D and allows for education and monitoring to prevent DKA at the onset of clinical T1D and consideration of immunomodulatory therapies. Follow-up of children who have tested positive for a single islet autoantibody makes it possible to detect or rule out progression to early-stage T1D.

Publication History

Article published online:
28 May 2025