Screening for pre-symptomatic T1D can significantly reduce the risk of DKA at diagnosis. Screening can also identify children who may benefit from interventions to delay/prevent progression from islet autoimmunity (IA) to diabetes. To help design a rational screening schedule, we analyzed data to determine the optimal ages to screen children for IA. Longitudinal data sets from birth cohort studies (DIPP, BABYDIAB, DiPiS, and DAISY) were harmonized for analyses. We analyzed the age of screening for multiple autoantibodies to insulin, GAD and IA-2 to maximize the sensitivity and positive predictive value (PPV) to predict development of T1D by age 15. Inverse probability censoring weighting was used to account for right censored outcomes. Cumulative sensitivity, dynamic specificity, positive and negative predictive values were used to describe the models. In the combined cohorts (n=6061), a one-time screening for multiple autoantibodies achieved a maximum sensitivity of 35% and a PPV of 70-80% when applied at age 3-5 yr. To increase the sensitivity above 50% and retain PPV >70%, two screenings should occur: at 2-3 yr and at 5-6 yr (Fig). Public health screening efforts to identify children progressing to T1D must make compromises based on feasibility, cost, optimal metrics. Our data represent a starting point for these considerations that should be customized based on the population’s underlying disease characteristics and public health infrastructure.
M. Ghalwash: None. V. Anand: None. W. Hagopian: Consultant; Self; Novo Nordisk Inc. M. Lundgren: None. M. Rewers: None. R. Veijola: None. A. Ziegler: None. J.L. Dunne: None.