AIMS/HYPOTHESIS: Age is known to be one of the most important stratifiers of disease progression in type 1 diabetes. However, what drives the difference in rate of progression between adults and children is poorly understood. Evidence suggests that many type 1 diabetes disease predictors do not have the same effect across the age spectrum. Without a comprehensive analysis describing the varying risk profiles of predictors over the age continuum, researchers and clinicians are susceptible to inappropriate assessment of risk when examining populations of differing ages. We aimed to systematically assess and characterise how the effect of key type 1 diabetes risk predictors changes with age. METHODS: Using longitudinal data from single- and multiple-autoantibody-positive at-risk individuals recruited between the ages of 1 and 45 years in TrialNet’s Pathway to Prevention Study, we assessed and visually characterised the age-varying effect of key demographic, immune and metabolic predictors of type 1 diabetes by employing a flexible spline model. Two progression outcomes were defined: participants with single autoantibodies (n=4893) were analysed for progression to multiple autoantibodies or type 1 diabetes, and participants with multiple autoantibodies were analysed (n=3856) for progression to type 1 diabetes. RESULTS: Several predictors exhibited significant age-varying effects on disease progression. Amongst single-autoantibody participants, HLA-DR3 (p=0.007), GAD65 autoantibody positivity (p=0.008), elevated BMI (p=0.007) and HOMA-IR (p=0.002) showed a significant increase in effect on disease progression with increasing age. Insulin autoantibody positivity had a diminishing effect with older age in single-autoantibody-positive participants (p