Type 1 diabetes (T1D) is an autoimmune condition characterized by the destruction of insulin-producing pancreatic beta cells. Detecting islet autoantibodies in children at risk for T1D is crucial for early intervention and timely management. This study proposes a novel two-stage islet autoantibody evaluation approach to enhance the accuracy of T1D prediction in childhood.
A cohort of 500 children, aged 2-12 years, with a familial history of T1D or genetic predisposition, were enrolled in this prospective study. In the first stage, samples were screened for the presence of glutamic acid decarboxylase (GAD) and insulinoma-associated-2 (IA-2) autoantibodies using highly sensitive and specific assays. Participants with positive results proceeded to the second stage, where zinc transporter 8 (ZnT8) and islet cell autoantibodies (ICA) were further assessed. Follow-up evaluations were conducted annually to monitor autoantibody status and glycemic parameters. Of the initial cohort, 78 children exhibited positivity for either GAD or IA-2 autoantibodies in the first stage. In the second stage, 32 participants were confirmed positive for ZnT8 or ICA autoantibodies. The combined evaluation identified 30 cases of confirmed autoimmunity. Over the subsequent five years, 28 of these children progressed to clinical onset of T1D. The two-stage approach demonstrated a significantly improved positive predictive value (PPV) compared to single-stage screening methods. The implementation of a two-stage islet autoantibody evaluation approach enhances the accuracy of T1D prediction in childhood. By incorporating assessments for GAD, IA-2, ZnT8, and ICA autoantibodies, this method provides a robust framework for identifying children at higher risk for developing T1D. Early intervention strategies, initiated upon positive autoantibody status, hold the potential to delay or prevent clinical onset, ultimately improving the long-term outcomes for children predisposed to T1D.