Identifying High-Risk Atrial Fibrillation in Diabetes: Evidence from Nomogram and Plasma Metabolomics Analysis

Background: Diabetes significantly increases the risk of atrial fibrillation (AF), but identifying high-risk individuals remains a clinical challenge. This study aimed to improve AF risk stratification in diabetic patients through a combination of clinical modeling and untargeted metabolomic analysis. Methods: A clinical risk score was developed using data from the National Health and Nutrition Examination Survey (NHANES) and validated in an independent cohort from Tongji Hospital. Its association with long-term outcomes and its ability to predict AF recurrence after catheter ablation were assessed in follow-up studies. Additionally, untargeted plasma metabolomics was performed in a subset of diabetic patients with and without AF to explore underlying mechanism. Results: The risk score showed good predictive performance in both the development and validation cohorts and was significantly associated with clinical prognosis. When combined with left atrial diameter and AF type, it also improved the prediction of AF recurrence after ablation. Metabolomic profiling revealed notable disturbances in energy metabolism, heightened inflammatory activity, and elevated stress responses in AF patients, indicating a distinct metabolic risk profile. Conclusions: This study provided two approaches to identify high-risk AF in diabetic patients, discussed the underlying pathophysiological mechanisms, and compared their characteristics and applications. And integrated strategies could improve AF risk stratification and personalized management in the diabetic.