Cardiometabolic risk status modifies the associations between remnant cholesterol with incident diabetes: evidence from two East Asian cohorts

Background: High remnant cholesterol (RC) frequently accompanies other traditional cardiometabolic risk factors (CMRF) during the progression of metabolic-related diseases. This study aims to differentiate the effects of traditional CMRF and to analyze the role of RC in the development of diabetes mellitus (DM). Methods: = 12,489) cohorts, stratified by CMRF status. The association between RC and DM was assessed using Cox regression models. Further exploration of the relationship was conducted using restricted cubic splines (RCS), extreme gradient boosting (XGboost), receiver operating characteristic (ROC) analysis, and mediation analysis. Sensitivity to unmeasured confounding was evaluated using E-value analysis. Results: RC was significantly associated with DM only in individuals with CMRF in both cohorts, and the association was nonlinear. In the Chinese cohort, DM risk increased when RC exceeded 0.5 mmol/L, while a saturation effect was observed in the Japanese cohort above 1.1 mmol/L. RC showed better predictive performance compared to LDL-C and total cholesterol in predicting DM risk among individuals with CMRF (AUC 0.606 and 0.647 in Chinese and Japanese cohorts, respectively). CMRF mediated 76.3 and 66.3% of the RC-DM association in the Chinese and Japanese cohorts. Conclusion: RC is nonlinearly associated with the incidence of DM in individuals with CMRF, primarily promoting its onset through the presence of CMRF.