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

<p dir="ltr">Objective</p><p dir="ltr">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.</p><p dir="ltr">Research Design and Methods</p><p dir="ltr">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.</p><p dir="ltr">Results</p><p dir="ltr">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.</p><p dir="ltr">Conclusion</p><p dir="ltr">Autoantibody-positive adult relatives exhibit distinct autoantibody trajectories and progression risks compared to children, suggesting the need for tailored monitoring and intervention strategies.</p><p> </p><p><br></p>