Screening Children for Early-Stage Type 1 Diabetes

Importance: Detecting type 1 diabetes in presymptomatic stages is essential for therapies aimed at delaying clinical onset. Objective: To estimate early-stage (stage 1 or 2) type 1 diabetes prevalence and disease progression to clinical (stage 3) type 1 diabetes in children in a population-based screening study. Design, Setting, and Participants: From February 2015 to July 2025, children living in Bavaria, Germany, were screened for early-stage type 1 diabetes. Screening was conducted by 716 primary care pediatricians. Screening was performed once in children aged 1.75 to 5.99 years until March 2019 and was subsequently expanded to include up to 2 screenings in children aged 1.75 to 10.99 years. Families of children with early-stage disease were offered diabetes education, metabolic staging, and longitudinal monitoring in 18 specialized diabetes centers. Exposures: Measurement of islet autoantibodies. Main Outcomes and Measures: The primary outcome was early-stage type 1 diabetes, defined as 2 or more autoantibodies against insulin, glutamic acid decarboxylase, islet antigen-2, or zinc transporter 8 confirmed in consecutive blood samples, with categorization into stages 1 (normoglycemia) and 2 (dysglycemia) and progression to clinical (stage 3) diabetes. Results: Among 220 476 enrolled children (median [IQR] age, 3.1 [2.2-5.0] years; 106 952 [48.7%] females), 590 had presymptomatic early-stage type 1 diabetes at first screening (adjusted population frequency, 0.3% [95% CI, 0.28%-0.32%]) with prevalences of 0.23% for stage 1 and 0.06% for stage 2 type 1 diabetes. Repeat screening in 11 726 children after a median of 3.3 years identified 29 additional cases. During a median follow-up of 5.7 years, 212 children with an early-stage diagnosis at first screening, 5 with a diagnosis at rescreening, and 43 without an early-stage diagnosis developed clinical (stage 3) diabetes. Five-year progression from early-stage to clinical diabetes was 36.2% (95% CI, 31.2%-40.8%; annualized rate, 9.6%), and not significantly different between children with and without a first-degree family history (P = .54). Conclusions and Relevance: General population screening of children identified early-stage type 1 diabetes and similar progression rates to clinical diabetes between children with and without a first-degree family history. These findings inform disease-modifying therapy trials and suggest that screening can be considered beyond genetically selected populations. Trial Registration: ClinicalTrials.gov Identifier: NCT04039945.