Abstract
BACKGROUND: Insulin resistance (IR) serves as a core pathophysiological factor among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and has an adverse impact on prognosis. As a reliable indicator of IR, the estimated glucose disposal rate (eGDR) is associated with cardiometabolic risk and mortality. However, the prognostic significance of eGDR in MASLD remains unclear. This study aims to examine the association between eGDR and cause-specific mortality in patients with MASLD. METHODS: Totally 6,847 patients with MASLD were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Patients were divided into four groups based on eGDR quartiles. The study outcomes were all-cause, cardiovascular and diabetes mortality. Restricted cubic splines (RCS) and the Cox proportional hazard model were used to evaluate the associations between eGDR and outcomes. Receiver operating characteristic (ROC) analyses were conducted to show its predictive ability for outcomes. Subgroup analyses were conducted to evaluate the robustness of performance. RESULTS: During the median follow-up of 8.8 years, 19.6% patients (n = 1,345) experienced death, with 6.5% (n = 443) cardiovascular mortality, and 1.3% (n = 89) diabetes mortality. After adjusting for confounders, higher eGDR level was significantly associated with lower risk of all-cause mortality (HR = 0.94, 95% CI: 0.92-0.97, P < 0.001), cardiovascular mortality (HR = 0.90, 95% CI:0.85-0.95, P < 0.001), and diabetes mortality (HR = 0.70, 95% CI: 0.62-0.80, P < 0.001). ROC analyses showed that the eGDR had a significant but modest predictive performance for all-cause mortality (AUC = 0.606) and cardiovascular mortality (AUC = 0.631), with a moderate performance for diabetes mortality (AUC = 0.729). Among different subgroups, the association between the eGDR and the risk of cause-specific mortality was similar to the main results. CONCLUSION: Higher eGDR levels are independently associated with reduced risks of all-cause, cardiovascular, and diabetes mortality among patients with MASLD, highlighting the prognostic relevance of insulin resistance in this population. The modest discriminative performance of eGDR further supports its role in cardiometabolic risk stratification.