Comparative associations of the TyG index and HOMA2-IR with 6-month outcomes after moderate-to-severe traumatic brain injury: a single-center retrospective cohort study.

Background: The triglyceride glucose (TyG) index and the homeostatic model assessment 2 of insulin resistance (HOMA2-IR) are both valid markers for assessing insulin resistance (IR) and may serve as early metabolic biomarkers associated with outcomes in patients with moderate-to-severe traumatic brain injury (msTBI). This study was designed to directly compare the TyG index and HOMA2-IR regarding their associations with 6-month outcomes in msTBI patients. Methods: This study conducted a single-center, retrospective cohort of 362 consecutive patients with msTBI admitted to the Jiangyin Clinical College of Xuzhou Medical University. Six-month outcomes were evaluated using the Glasgow Outcome Scale-Extended (GOSE) and dichotomized as favorable (GOSE ≥ 5) or unfavorable (GOSE ≤ 4). In this study core IMPACT-CT variables were collected (Glasgow Coma Scale score, age, pupillary reactivity, and Marshall CT score), sex, and two IR indices. Analyses included univariable comparisons by the outcome group, evaluation of the correlation between the TyG index and HOMA2-IR, generalized additive models (GAMs) to assess potential non-linearity, and multivariable models with adjusted restricted cubic splines (RCSs) to confirm and characterize non-linear associations of the TyG index and HOMA2-IR with outcome and to clarify their independent contributions. Clinical utility was evaluated using decision curve analysis (DCA) to determine net benefit. Results: All core IMPACT-CT variables and both IR indices differed significantly by the outcome group. The TyG index and HOMA2-IR were moderately correlated. GAMs indicated a mildly non-linear negative association between the TyG index and an approximately linear negative association between HOMA2-IR and the outcome. RCSs confirmed that both indices were strongly associated with outcome and similarly improved discrimination, whereas the TyG index showed greater independent contribution and a broader range of net benefit on DCA. Conclusion: Both the TyG index and HOMA2-IR were significantly associated with unfavorable outcomes and improved the performance of models based on core IMPACT-CT variables in this single-center retrospective cohort study. Although their overall discrimination was similar, the TyG index showed a modest but consistent advantage in independent contribution and net clinical benefit, and it was easier to implement in clinical practice.