Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index’s prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P < 0.01) and a 79% higher risk of ICU mortality (HR 1.79 [95% CI 1.28 to 2.51], P < 0.001). Model 3 showed that ICU mortality risks for Q4, Q3, and Q2 were 240%, 75%, and 33% higher, respectively (HR 3.40 [95% CI 2.24 to 5.16], P < 0.001; HR 1.75 [95% CI 1.16 to 2.63], P = 0.007; HR 1.33 [95% CI 1.20 to 1.53], P < 0.001). RCS regression analysis identified a nonlinear association between the TyG index and mortality (overall P < 0.001; P for nonlinearity < 0.001, with an inflection point at 8.9). Subgroup analysis showed that the effect size and direction were consistent across different subgroups, suggesting the stability of the results. This study demonstrates that a higher TyG index is significantly associated with increased in-hospital and ICU mortality risk in critically ill sepsis patients, with evidence of non-linear correlation. Therefore, the TyG index helps identify the mortality prognosis of sepsis patients in the ICU.
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