Development and Validation of a Novel Risk Prediction Model for Incident Diabetic Foot Complications: A Large, Longitudinal, Population-Based Machine Learning Study

OBJECTIVE: Diabetic foot complications (DFCs) are common diabetes complications. Existing tools for predicting incident DFCs remain insufficient. This study aimed to develop and validate a novel machine learning-based model for incident DFC prediction. APPROACH: Using UK Biobank data, we built a longitudinal incident DFC cohort, with DFCs identified using International Classification of Diseases codes. Clinical features were screened by Cox models, and a machine learning model (DFC-Clin) was developed using fivefold cross-validation and leave-one-center-out validation. Performance was compared with diabetic foot risk stratification tools using the DeLong test. A web-based tool and risk stratification system were also developed. RESULTS: Among 502,175 participants, 29,766 individuals formed the incident cohort, with 1,252 incident DFC events. Demographics, blood markers, lifestyle factors, and comorbidities were selected to construct DFC-Clin, with glycated hemoglobin and body mass index emerging as the most predictive features. The model showed improved discrimination compared with existing risk stratification tools, achieving area under the receiver operating characteristic curves of 0.782 ± 0.042, 0.766 ± 0.042, and 0.747 ± 0.021 for 5-year, 10-year, and overall incident DFC prediction, respectively. INNOVATION: DFC-Clin is a machine learning model for incident DFC prediction that uses accessible clinical features from a large population-based cohort and is coupled with a web-based application and risk stratification system. CONCLUSION: DFC-Clin estimates the risk of incident DFC across multiple time horizons and demonstrates improved discrimination compared with existing approaches. The web-based application and stratification framework are intended to support risk identification and preventive decision-making. Further studies are required for clinical deployment and evaluation on more clinical outcomes, including amputations, recurrence, and health care costs.[Figure: see text][Figure: see text][Figure: see text].