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Chronic Kidney Disease and Diabetes / Diabetes, Cardiovascular Risks, and Lipoproteins · Journal article
Frontiers in Endocrinology · August 17, 2026
Well-designed and adequately powered for the question it asks.
This meta-analysis of 80 observational studies demonstrates that TyG-derived indices, particularly TyG-WC, TyG-WHtR, and CTI, show stronger associations with cardiovascular mortality and CVD incidence than the TyG index alone in populations with cardiovascular-kidney-metabolic disease stages 1–3. The associations were non-significant in stage 0 and dose-response analyses revealed a non-linear U-shaped relationship with all-cause mortality but monotonic increase for CVD incidence.
Systematic review and dose-response meta-analysis of observational studies. Populations with cardiovascular-kidney-metabolic syndrome stages 0–3; stratified analyses by CKM stage and obesity status. Intervention: Exposure to triglyceride-glucose index and derived indices (TyG-BMI, TyG-WC, TyG-WHtR, CTI). Compared with: Highest versus lowest category; per 1-SD increment in continuous analysis. Multiple countries (not specified in abstract).
TyG-WC in highest category: RR = 1.52 (95% CI: 1.35–1.70) for CVD mortality CTI associated with 57% increase in incident CVD: RR = 1.57 (95% CI: 1.33–1.85) TyG-BMI predicted 51% CVD risk increase: RR = 1.51 (95% CI: 1.36–1.67) but non-significant for mortality
TyG-WC in highest category: RR = 1.52 (95% CI: 1.35–1.70) for CVD mortality TyG-BMI predicted 51% CVD risk increase: RR = 1.51 (95% CI: 1.36–1.67) but non-significant for mortality
These findings suggest that TyG-derived indices, especially TyG-WC, TyG-WHtR, and CTI, may be more useful than TyG alone for cardiovascular risk stratification in CKM populations. However, the observational design precludes causal inference and the indices remain surrogate markers; their clinical utility requires prospective validation and comparison with established risk factors in clinical practice.
Rigorous meta-analysis of 80 observational studies with dose-response modelling, clear effect sizes and confidence intervals, but observational design and surrogate indices limit practice-changing status.
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These findings suggest that TyG-derived indices, especially TyG-WC, TyG-WHtR, and CTI, may be more useful than TyG alone for cardiovascular risk stratification in CKM populations. However, the observational design precludes causal inference and the indices remain surrogate markers; their clinical utility requires prospective validation and comparison with established risk factors in clinical practice.
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Background The associations of the triglyceride-glucose (TyG) index and its derived indices with the progression of cardiovascular-kidney-metabolic (CKM) syndrome remain poorly elucidated. Methods We conducted a systematic review and dose-response meta-analysis of 80 observational studies encompassing populations within CKM stages 0–3, evaluating TyG, TyG-BMI, TyG-WC, TyG-WHtR, and CTI for all-cause mortality, cardiovascular disease (CVD) mortality, and CVD incidence (including stroke, coronary heart disease, heart failure and major adverse cardiovascular events). A one-stage mixed-effects approach was used, supplemented by subgroup, meta-regression, leave-one-out, and trim-and-fill analyses. Results In both continuous (per 1-SD increment) and categorical (highest vs. lowest) analyses, TyG-derived indices generally demonstrated stronger risk associations with target outcomes than TyG alone. Notably, CTI, TyG-WC, and TyG-WHtR exhibited higher risk associations. In the highest-category analysis, TyG-WC yielded the most pronounced risk for CVD mortality (RR = 1.52, 95% CI: 1.35–1.70, 95% PI: 1.26–1.82). CTI was associated with a 57% increase in incident CVD (RR = 1.57, 95% CI: 1.33–1.85, 95% PI: 1.00–2.46). Conversely, TyG-BMI showed non-significant associations with mortality-related outcomes (P 0.05), though it predicted a 51% risk increase for incident CVD (RR = 1.51, 95% CI: 1.36–1.67, 95% PI: 1.05–2.16). Subgroup analysis indicated that these positive associations were pronounced in CKM stages 1–3 but entirely non-significant in stage 0 and the obesity subgroup had a significant impact on the risk of mortality. Dose-response analyses revealed a significant non-linear U-shaped association of the TyG index with all-cause mortality (Pnon-linearity 0.0001; nadir = 8.90). For CVD mortality, the overall association was significant (Poverall = 0.005; nadir = 8.91), whereas a monotonic increasing trend was observed for CVD incidence (Poverall = 0.0014). In sensitivity analyses excluding participants with cancer or consumptive diseases at baseline, as well as those in CKM stage 0, the U-shaped patterns remained stable (mortality nadir shifted to 9.1). Conclusions TyG-derived indices, particularly TyG-WC, TyG-WHtR, and CTI, show stronger risk associations than the TyG index for cardiovascular risk assessment in CKM populations, whereas the clinical utility of TyG-BMI is relatively limited. Moderate elevations in TyG were associated with lower mortality risk within a certain range, though the non-linear association was confirmed only for all-cause mortality. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251111362, identifier CRD420251111362.
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