2968-LB: Multicenter Study for Presymptomatic Type 1 Diabetes Screening in First-Degree Relatives: A Prospective Cohort Study

Introduction and Objective: Type 1 diabetes (T1D) is an autoimmune disorder marked by islet autoantibodies. First-degree relatives (FDRs) of individuals with T1D have a 10-15-fold higher risk of developing T1D than the general population. Screening for four autoantibodies—glutamic acid decarboxylase (anti-GAD), protein tyrosine phosphatase (anti-IA2), insulin (IAA), and Zinc Transporter 8 (anti-ZnT8)—enables early detection of T1D and reduces diabetic ketoacidosis at diagnosis. Positivity for two or more autoantibodies confirms presymptomatic T1D, while one autoantibody identifies individuals at risk. We evaluated the feasibility and outcomes of systematic autoantibody screening in Madrid, Spain. Methods: This multicenter study was performed in three public tertiary hospitals. A REDCap-based platform captured standardized clinical data from pediatric patients with T1D and their FDRs. Autoantibodies were measured in 847 FDRs from 509 patients. Participants with ≥2 autoantibodies underwent evaluation including HbA1c, fasting glucose, OGTT, and 14 days of glucose monitoring. Results: FDRs included parents (59.5%) and siblings (40.5%). Mean age was 36.4 years (95% CI 16.8-55.9) in parents and 12.6 years (95% CI 11.5-13.8) in siblings. At least one positive autoantibody was detected in 190 relatives (22.4%; 95% CI 19.6-25.3), and 29 (3.5%; 95% CI 2.3-5.0) had ≥2 autoantibodies. Anti-IA2 was most frequently detected (10%; 95% CI 8.5-12.9), followed by IAA, anti-GAD65, and anti-ZnT8, although ZnT8 was unavailable in 25% of participants. Among relatives with ≥2 autoantibodies, dysglycemia was identified in five children and three adults. One adult was reclassified from type 2 to type 1 diabetes after screening. Conclusion: Systematic multicenter screening of FDRs is feasible and identifies a substantial proportion of individuals with islet autoimmunity. Early detection enables identification of dysglycemia, diagnostic reclassification, and access to disease-modifying therapies. Disclosure P. Perez Segura: None. M. Güemes: None. M. Roldán Martín: None. J. Cruz-Rojo: Advisory Panel; Ended; Sanofi. Other - We have received funding to implement a multicenter project for collecting diabetes-screening data from relatives of patients with type 1 diabetes mellitus; Ended; Sanofi. M. De Cos Igartua: Other - Sanofi, through my hospital's foundation, has funded a pancreatic autoimmunity screening project which ended in 2025.; Ended; Sanofi. K. Alkadi Fernandez: None. M. Martin Frias: None. I. Lázaro Rodríguez: None. J. Argente: None. P. Enes Romero: None.