Triglyceride-glucose related indices, cardiometabolic multimorbidity, and risk of incident osteoarthritis: A prospective cohort study in UK Biobank

Background: Metabolic dysfunction may contribute to osteoarthritis (OA), but routine markers for identifying future OA risk remain limited. Objective: To examine associations of triglyceride-glucose (TyG) and adiposity-integrated TyG indices with hospital-recorded incident OA, and whether these associations differed by cardiometabolic disease (CMD) burden. Design: Prospective cohort study using UK Biobank data. Methods: We included 255,232 participants without baseline OA and with complete exposure, covariate, and selected metabolomic data. Baseline TyG, TyG-body mass index (BMI), TyG-waist circumference (WC), and TyG-waist-to-height ratio (WHtR) were analyzed in quartiles. CMD burden was categorized as no CMD, one CMD, or cardiometabolic multimorbidity (CMM). Hospital-recorded incident OA was identified from linked hospital inpatient records using ICD-10 codes M15-M19. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, socioeconomic, and lifestyle factors. Restricted cubic spline, stratified, and joint exposure analyses were performed. Results: During follow-up, 43,554 participants developed OA. Compared with the lowest quartile, the highest quartile was associated with a higher risk of hospital-recorded incident OA for TyG-BMI (HR 2.18, 95% CI 2.12-2.24), TyG-WC (HR 2.14, 95% CI 2.08-2.21), and TyG-WHtR (HR 2.00, 95% CI 1.94-2.06), whereas TyG alone showed only a weak association (HR 1.03, 95% CI 1.00-1.06). CMD burden was independently associated with OA risk (one CMD: HR 1.37, 95% CI 1.29-1.46; CMM: HR 1.44, 95% CI 1.31-1.58). Across CMD strata, the strongest associations were observed among participants with CMM, with HRs of 2.05 (95% CI 1.61-2.61), 1.99 (95% CI 1.61-2.46), and 1.97 (95% CI 1.56-2.49) for TyG-BMI, TyG-WC, and TyG-WHtR, respectively. No statistically significant interactions were detected. Conclusion: Adiposity-integrated TyG indices and greater CMD burden were associated with hospital-recorded incident OA, whereas TyG alone showed only a weak association. Joint-category analyses showed higher observed risk estimates among participants with both characteristics, without evidence of multiplicative interaction.