Abstract
BACKGROUND: Early detection of prediabetes is crucial for diabetes prevention, yet it remains challenging due to its asymptomatic nature and low screening rates. This study aimed to develop and rigorously validate artificial intelligence (AI) models to identify individuals with prediabetes solely using electrocardiograms (ECGs). METHODS: We defined prediabetes/diabetes based on fasting plasma glucose ≥ 110 mg/dL, hemoglobin A(1c) ≥ 6.0%, or ongoing diabetes treatment. From a primary cohort of 16,766 health checkup records, 269 ECG features were extracted to develop a novel AI model. The final model was subsequently evaluated using an internal held-out test dataset and an independent external validation cohort (n = 2,456). SHAP (SHapley Additive exPlanations) was applied to assess feature importance and clinical interpretability. RESULTS: The best-performing model, a LightGBM-based algorithm we termed DiaCardia, achieved an area under the receiver operating characteristic curve (AUROC) of 0.851 in the internal test dataset (sensitivity: 85.7%, specificity: 70.0%). The model demonstrated robust generalizability, achieving an AUROC of 0.785 in the external validation cohort. Furthermore, DiaCardia maintained substantial predictive ability (AUROC: 0.789) after adjustment for six major confounders using propensity score matching. Higher R-wave amplitude in leads aVL and I, and smaller peak interval dispersion were prominent predictors. Notably, a version of DiaCardia using only single-lead (lead I) ECG data achieved a comparable AUROC of 0.844 (sensitivity: 82.3%; specificity: 70.2%). CONCLUSIONS: This study establishes that an AI model, DiaCardia, can accurately identify individuals with prediabetes from an ECG alone, with performance that is robust across different patient cohorts and independent of major clinical confounders. Our highly generalizable, single-lead DiaCardia model offers a promising solution for scalable prediabetes screening via wearable devices, potentially enabling early, home-based detection and transforming diabetes prevention strategies.