Association of the triglyceride-glucose index and its combination with obesity indices with cardio-renal-metabolic multimorbidity: two decades of follow-up in the Tehran Lipid and Glucose Study.

Abstract

Objective: To investigate the associations between the triglyceride-glucose (TyG) index and its obesity-related derivatives with the risk of incident cardio-renal-metabolic multimorbidity (CRMM) in a Middle Eastern adult population initially free of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD).

Methods: In this prospective cohort analysis of 5845 Iranian adults from the Tehran Lipid and Glucose Study, we evaluated the associations of the TyG index and its combinations with body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), and waist-hip ratio (WHR) with the incidence of CRMM. Multivariable Cox proportional hazards models were used to estimate the associations between TyG indices and CRMM risk. The Wald test was used to formally compare the effect sizes of each TyG-related index with that of the TyG index in multivariable models. The predictive performance of these indices was evaluated using Harrell's C-index and the integrated discrimination improvement (IDI).

Results: Over a median follow-up of 15.3 years (IQR: 11.9-16.4), 344 individuals (5.9%) developed CRMM. Restricted cubic spline models demonstrated significant linear associations between TyG indices and CRMM risk. The corresponding HRs (95% CI) per 1-SD increase were 1.41 (1.24-1.60) for the TyG index, 1.52 (1.36-1.71) for TyG-BMI, 1.57 (1.38-1.78) for TyG-WC, 1.57 (1.38-1.78) for TyG-WHtR, and 1.42 (1.24-1.63) for TyG-WHR (all P < 0.001). The inclusion of anthropometric measures alongside the TyG index did not substantially enhance its association with CRMM risk (all P for differences ≥ 0.05). Incremental predictive performance analyses showed modest but statistically significant improvements when adding TyG and TyG-obesity indices to conventional risk factors (all P < 0.05), whereas incorporating anthropometric-based indices to a model already containing TyG did not yield additional predictive improvement (all P > 0.05). The majority of associations remained robust after adjustment for homeostatic model assessment of insulin resistance and in sensitivity analyses. The association between TyG-WHR and CRMM was more pronounced among non-obese than obese individuals (P for interaction < 0.001).

Conclusions: Higher levels of TyG and TyG-obesity indices were independently associated with an increased risk of CRMM; however, incorporating obesity indices did not confer substantial improvement over the TyG index alone.