A type 1 diabetes prediction model has utility across multiple screening settings with recalibration
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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 visualization of individualized risk prediction. Methods We developed and refined 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 7,798 TEDDY and 4,068 TrialNet participants, with 305 (4%) and 1,373 (34%) developing type 1 diabetes, respectively. The combined model showed similar discriminative ability in autoantibody-positive individuals across TEDDY and TrialNet (p = 0.14), but inferior calibration in TrialNet (Brier score 0.40 [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 of type 1 diabetes genetic risk score, family history, age, and autoantibody status accurately predicts type 1 diabetes risk, but may need recalibration according to screening stategy.
