Interaction and Joint Effects of Inflammation and Triglyceride–Glucose ( TyG ) Index on Hyperuricemia Risk and the Mediating Role of TyG : A Cross‐Sectional Study

BACKGROUND: The chronic inflammation and insulin resistance (IR) are implicated in hyperuricemia (HUA) pathogenesis, while their interplay remains inadequately characterised. This study aimed to investigate their independent, interactive, and combined effects on HUA risk and serum uric acid (UA) levels, and to quantify the mediating effect of IR in the Southern Chinese population. METHODS: A cross-sectional study was conducted among 5307 Chinese adults. The triglyceride-glucose (TyG) index served as an alternative marker for IR, and a modified inflammation (mINFLA) score, comprising white blood cell (WBC) count, platelet (PLT) count, and the neutrophil-to-lymphocyte ratio (NLR), was used to assess systemic low-grade inflammation. The multivariable logistic and linear regression models were employed to explore the associations of the TyG index and mINFLA score with HUA risk and UA levels, and the interaction effects and mediating role of the TyG index were further assessed. Subgroup analyses were stratified by age, sex, and disease status. RESULTS: Among 5307 Chinese adults, a higher TyG index and a higher mINFLA score were significantly associated with an increased HUA risk and elevated UA levels, demonstrating significant dose-response relationships (p for trend < 0.001). A significant interaction was observed between the TyG index and mINFLA score in relation to HUA risk and UA levels. Participants exhibiting both high TyG index and mINFLA score had the highest HUA risk and UA levels. Notably, mediation analysis revealed that the TyG index significantly explained 15.4% of the association between the mINFLA score and HUA risk, and 14.5% of the association with UA levels. CONCLUSION: Chronic inflammation is an independent risk factor for hyperuricemia, with insulin resistance serving as a key mediating factor. Furthermore, these two factors exhibit a significant joint effect on hyperuricemia risk. These findings underscore the importance of simultaneously considering both insulin resistance and chronic inflammation in hyperuricemia prevention and management.