Contrasting Adult vs. Pediatric populations in a cohort of at risk relatives: The TrialNet Pathway to Prevention Study

Objective Adults represent over half of incident type 1 diabetes, yet research on disease progression predominantly focuses on at-risk children. We aimed to compare autoantibody screening outcomes and type 1 diabetes progression in adults versus children. Research Design and Methods We studied 135,914 children (<18 years) and 99,795 adult relatives of individuals with type 1 diabetes screened in the TrialNet Pathway to Prevention study. In autoantibody positive participants, we compared progression rates, associations with risk factors, and performance of metabolic risk scores. Results Adults were more likely than children to screen positive for a single autoantibody (4.0% vs 2.6%) but less likely for multiple autoantibodies (0.83% vs 2.8%; p<0.001). Progression to stage 3 disease was lower in adults with single autoantibody positivity or stage 1 type 1 diabetes vs. children (5-year risks: single autoantibody, adults 8.2% vs children 22%; p<0.001; stage 1, adults 17% vs children 47%; p<0.001). However, adults with stage 2 type 1 diabetes at initial staging OGTT showed comparable 5-year progression risks to children (78% for both groups). A higher proportion of adults progressing to clinical diabetes were single autoantibody positive (40% v 15%, p<0.0001), these individuals were commonly single GAD positive, and had lower type 1 but higher type 2 genetic risk scores compared to multiple autoantibody-positive adults. HbA1c and established risk indices more effectively identified progressors in adults compared to children. Conclusion Autoantibody-positive adult relatives exhibit distinct autoantibody trajectories and progression risks compared to children, suggesting the need for tailored monitoring and intervention strategies.