Associations Between Metabolic Syndrome Index, Systemic Inflammatory Index, and Arthritis Subtype in the U.S. and Chinese Adults: A Mediation Analysis
TL;DR
This cross‐population study demonstrates that TyG and TyG–BMI indices are positively and dose‐dependently associated with multiple arthritis subtypes, with systemic inflammation serving as a partial mediator.
Abstract
Background Arthritis represents a spectrum of chronic inflammatory conditions, with growing evidence linking metabolic dysregulation to disease pathogenesis. While composite metabolic indices have been proposed as potential markers for arthritis, their associations with specific disease subtypes and applicability across diverse ethnic populations remain insufficiently characterized. Methods This study analyzed data from 15,015 participants in the U.S. National Health and Nutrition Examination Survey (NHANES) and 3848 subjects from a Chinese hospital‐based cohort. Associations between triglyceride‐glucose (TyG) index/TyG–body mass index (TyG–BMI) and arthritis subtypes (osteoarthritis [OA], rheumatoid arthritis [RA], and gout) were assessed using multiple logistic regression and restricted cubic splines (RCS) with adjustment for age and gender. Mediation analysis evaluated the role of the systemic immune‐inflammation index (SII). Predictive performance was compared using area under the curve (AUC). Results Elevated TyG and TyG–BMI were significantly associated with higher odds of multiple arthritis subtypes in both cohorts. In NHANES, the highest TyG quartile was linked to 26%–64% higher odds compared with the lowest quartile, while TyG–BMI showed stronger associations (ORs 2.25–2.76). Similarly, TyG–BMI was strongly associated with RA (OR = 4.77) and gout (OR = 5.46) in the Chinese cohort. Dose–response analyses confirmed significant nonlinear positive relationships between TyG/TyG–BMI levels and arthritis risk. Systemic inflammation mediated a substantial proportion of these associations (all p < 0.05). Predictive performance differed ethnically: TyG–BMI performed best in the U.S. cohort (AUCs 0.599–0.617), whereas the TyG index was superior in the Chinese cohort (AUCs 0.647–0.719). Conclusions This cross‐population study demonstrates that TyG and TyG–BMI indices are positively and dose‐dependently associated with multiple arthritis subtypes, with systemic inflammation serving as a partial mediator. These findings underscore the utility of TyG and TyG–BMI indices in identifying at‐risk individuals for targeted early intervention and personalized management of arthritis.