Association between triglyceride-glucose index, triglyceride-glucose-body mass index and cardiometabolic multimorbidity: the mediating role of leukocytes among Chinese middle-aged and older adults—a nationwide prospective cohort study

Cardiometabolic multimorbidity (CMM) is a growing global health burden linked to markedly elevated mortality, yet integrative biomarkers for early risk identification are lacking. The triglyceride-glucose index (TyG) and TyG–body mass index (TyG-BMI) are accessible surrogates of insulin resistance. However, their comparative value for predicting CMM and the role of inflammation remain unclear. Using five waves (2011–2020) of the China Health and Retirement Longitudinal Study (CHARLS), we analyzed 7,731 participants aged 45 years and above who met the primary baseline eligibility criteria. CMM was defined as the coexistence of at least two of three conditions: heart disease, stroke, and diabetes. Cox regression was used to examine associations with incident CMM. Additional analyses assessed selection related to baseline missing data, applied broader available diabetes criteria at baseline, and excluded CMM events occurring within the first 2 years. Regression-based mediation analysis examined white blood cell count (WBC) and high-sensitivity C-reactive protein. During follow-up, 497 participants developed CMM. After multivariable adjustment, both indices were positively associated with CMM (per-unit TyG: HR 1.61, 95% CI 1.43–1.81; per-SD TyG-BMI: HR 1.47, 95% CI 1.37–1.58). Adding either index improved discrimination and reclassification. TyG-BMI yielded a modest but statistically significant increase in C-index relative to TyG (0.685 vs. 0.666; difference 0.019, 95% CI 0.006–0.032; P = 0.004). The TyG association was stronger among participants without hypertension (P for interaction = 0.001). Regression-based mediation estimates suggested small indirect effects through WBC, whereas high-sensitivity C-reactive protein showed no evidence of mediation. Results were materially unchanged in the broader-baseline-diabetes and 2-year landmark sensitivity analyses. Higher baseline TyG and TyG-BMI were associated with greater risk of incident CMM in middle-aged and older Chinese adults. TyG-BMI provided a modest statistical improvement in discrimination over TyG, but the clinical relevance of this difference requires external validation.Conclusions