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.