Association between estimated glucose disposal rate and cardiovascular disease prevalence and mortality outcomes in metabolic dysfunction-associated steatotic liver disease: a comparative analysis of insulin resistance markers.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), primarily driven by insulin resistance (IR), is emerging as a significant public health concern. While the estimated glucose disposal rate (eGDR), a novel marker of IR, could be useful in predicting adverse outcomes in diabetes, its role in MASLD remains unclear. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) collected from 1999 to 2018, and combined cross-sectional and cohort study designs to explore the associations between eGDR, cardiovascular disease (CVD) outcomes in US adults with MASLD. Here, MASLD was defined using the fatty liver index or hepatic steatosis index along with cardiometabolic risk factors. We applied survey-weighted logistic regression to evaluate CVD prevalence and used Cox proportional hazards models to assess mortality risk. We analysed nonlinear associations between eGDR, CVD, and mortality outcomes using restricted cubic splines. Lastly, we compared the predictive performance of eGDR with traditional IR markers, including the triglyceride-glucose (TyG) index and HOMA-IR, via C-statistics. Results: Logistic regression and Cox proportional hazards models showed that lower eGDR levels were consistently associated with increased risks of CVD prevalence (P < 0.001) and mortality (P < 0.001), even after adjusting for potential confoundersin both MASLD models. eGDR also outperformed TyG and HOMA-IR in predicting all-cause and CVD mortality (P < 0.001), underscoring its superior prognostic value in MASLD populations (P < 0.001). Moreover, incorporating eGDR into the baseline model significantly enhanced predictive accuracy and reclassification (P < 0.001), further validating its potential to improve risk prediction. Conclusions: Lower eGDR levels are associated with higher risks of CVD and mortality in MASLD. The eGDR outperforms traditional IR markers in predicting all-cause mortality and improves risk prediction models, highlighting its potential usefulness for clinical risk stratification in MASLD.