Artificial intelligence-enhanced electrocardiography for the prediction of future type 2 diabetes mellitus: a model-development and multicentre validation study

A significant proportion of type 2 diabetes cases remain undiagnosed despite screening advances, carrying substantial cardiometabolic risk. Artificial intelligence-enhanced electrocardiography (AI-ECG) detects subtle ECG changes in subclinical disease, potentially enabling opportunistic screening.

We developed AI-ECG Risk Estimator for Diabetes Mellitus (AIRE-DM), a convolutional neural network with discrete-time survival loss, for diagnosis of prevalent and prediction of incident type 2 diabetes. It was trained on 1 163 401 ECGs from 189 537 individuals from Beth Israel Deaconess Medical Center (BIDMC) and externally validated in UK Biobank (UKB; n = 65 606) and ELSA-Brasil (n = 13 739). AI-ECG Risk Estimator for Diabetes Mellitus demonstrated moderate discrimination for prevalent type 2 diabetes (area under the receiver operating characteristic curve: BIDMC 0.724, UKB 0.733, ELSA-Brasil 0.706) and incident type 2 diabetes (C-index: BIDMC 0.667, UKB 0.688, ELSA-Brasil 0.625). The highest AIRE-DM risk quartile had elevated incident diabetes risk vs. the lowest (hazard ratio: BIDMC 4.75, UKB 7.52, ELSA-Brasil 3.96). AI-ECG Risk Estimator for Diabetes Mellitus was non-inferior to the American Diabetes Association Diabetes Risk Test in BIDMC, with improved predictive accuracy when combined. In normoglycaemic patients, AIRE-DM was superior to glycated haemoglobin (HbA1c) for predicting incident diabetes in BIDMC and non-inferior in ELSA-Brasil. The highest risk quartile reached 5% cumulative type 2 diabetes mellitus incidence 5.4 years (BIDMC) and 4.8 years (ELSA-Brasil) earlier than the lowest risk quartile, after adjusting for HbA1c, age, and sex. Phenome- and genome-wide association studies revealed biologically plausible associations with glucose regulation, cardiac morphology, diastolic dysfunction, arterial stiffness, and lipid metabolism.

AI-ECG Risk Estimator for Diabetes Mellitus detects prevalent type 2 diabetes and predicts incident disease, uniquely identifying high-risk individuals within the normoglycaemic range. Combined with clinical scores or biomarkers, it enhances risk stratification, enabling earlier intervention.