Development and recalibration of a multivariable type 1 diabetes prediction model for type 1 diabetes across multiple screening studies.

BACKGROUND: Accurate type 1 diabetes prediction is important to facilitate screening for pre-clinical type 1 diabetes to enable potential early disease-modifying interventions and to reduce the risk of severe presentation with diabetic ketoacidosis. We aimed to assess the generalisability of a prediction model developed in children followed from birth. Additionally, we sought to create an application for easy calculation and visualisation of individualised risk prediction. METHODS: We developed and internally validated a stratified prediction model combining a genetic risk score, age, islet autoantibodies, and family history using data from children followed since birth by The Environmental Determinants of Diabetes in the Young (TEDDY) study. We tested the validity of the model through external validation in the Type 1 Diabetes TrialNet Pathway to Prevention study, which conducts cross-sectional screening in relatives of people with type 1 diabetes. We recalibrated the model by adjusting for baseline risk and selection criteria in TrialNet using logistic recalibration to improve calibration across all ages. RESULTS: The study included 7798 TEDDY and 4068 TrialNet participants, with 305 (4%) and 1373 (34%) developing type 1 diabetes, respectively. The stratified model showed similar discriminative ability in autoantibody-positive participants across TEDDY and TrialNet, but inferior calibration in TrialNet (Brier score 0.40 [95% CI 0.38,0.43]). Adjustment for baseline risk and selection criteria in TrialNet using logistic recalibration improved calibration across all ages (Brier score 0.16 [0.14,0.17]; p < 0.001). A web calculator was developed to visualise individual risk estimates ( https://t1dpredictor.diabetesgenes.org ). CONCLUSIONS: A stratified model incorporating the type 1 diabetes genetic risk score, family history, age, and autoantibody status can predict type 1 diabetes risk with improved accuracy, but may need recalibration depending on the screening strategy.