Contrasting Adult and Pediatric Populations in a Cohort of At-Risk Relatives in The T1D TrialNet Pathway to Prevention Study

OBJECTIVE More than half of incident type 1 diabetes (T1D) occurs in adults, yet research on disease progression predominantly focuses on at-risk children. We compared autoantibody screening outcomes and T1D progression in adults versus children. RESEARCH DESIGN AND METHODS We studied 135,914 children (aged <18 years) and 99,795 adult relatives of individuals with T1D 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 T1D than in 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 T1D at initial staging oral glucose tolerance test had 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% vs. 15%; P < 0.0001); these individuals commonly had single glutamic acid decarboxylase positivity and had lower type 1 but higher type 2 genetic risk scores compared with multiple autoantibody positive adults. HbA1c and established risk indices more effectively identified progressors in adults compared with children. CONCLUSIONS Autoantibody positive adult relatives have distinct autoantibody trajectories and progression risks compared with children, suggesting the need for tailored monitoring and intervention strategies.