1443-P: Natural History of Type 1 Diabetes (T1D)—Contrasting Adult vs. Pediatric At-Risk Populations

Introduction: Adults represent over half of incident T1D cases but most studies on risk prediction focus on children.

Methods: We studied 135,970 children (<18 years old) and 99,795 adult relatives in the TrialNet Pathway to Prevention study screened for autoantibody positivity (AB+). Kaplan Meier curves and log rank tests compare T1D progression. We tested discrimination of existing metabolic risk scores: Index60 (I60) and DPT1 (DPTRS) using area under time dependent receiver operating characteristic curve (ROC AUC).

Results: Adults had lower confirmed AB+ rates (adults 4.9% (n=4843); children 5.4% (n=7364), p < 0.001), particularly for multiple AB+ (adults 0.9% (n=939); children 3% (n=4062), p < 0.001). AB+ adults at all stages of disease exhibited lower 3 year progression risk compared to children (Table 1) but risk scores remained discriminative (DPTRS ROC AUC: adults 0.91 [0.87 - 0.94], children 0.86 [0.84 - 0.87]; I60: adults 0.87 [0.83 - 0.91], children 0.83 [0.82 - 0.85]).

Conclusion: Key differences and similarities between children and adult relatives are highlighted: fewer adults presented with early stage T1D (multiple AB+), progression rates were lower in AB+ adults, and those at highest risk can be identified with metabolic risk scores. Large datasets of AB+ adults are needed to refine and calibrate T1D prediction models in adults.

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