Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study

Q: What are the key findings of this study?

A one-standard deviation increase in the TyG-weight-adjusted waist index (TyG-WWI) was associated with a 43% higher risk of incident cardiometabolic multimorbidity (HR 1.43) across CKM stages 0-3.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 (n=646). Intervention: TyG-related indices (e.g., TyG-weight-adjusted waist index) vs. Reference values (lowest quartile or per standard deviation increase). Primary outcome: Incident cardiometabolic multimorbidity (CMM) (HR 1.43, 95% CI 1.20-1.70, p=<0.001).

Q: What does this research mean for the field?

Higher TyG-related indices, particularly TyG-WWI, are linearly associated with an increased risk of incident cardiometabolic multimorbidity across CKM stages 0–3. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate whether the triglyceride-glucose index and its anthropometry-based derivatives predict incident cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic stages 0–3.

Ankai Chen; Haosen Pan; Gang Liu; Xinxiang Dong; Xintao Chen; Fulai Sun; Sukhee Ahn; Liping Ren; Maoyun Miao

doi:10.1038/s41598-026-73597-2

October 17, 2026Scientific ReportsOpen Access

Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study

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Key result

Higher TyG-WWI linked to ~43% higher risk of cardiometabolic multimorbidity per SD.

HR 1.43
95% CI 1.20-1.70
P<0.001
n=646

Why the study?

The predictive performance of the TyG index and its anthropometry-based derivatives for cardiometabolic multimorbidity across early CKM syndrome stages 0–3 remains unclear.

Do TyG-related indices predict incident cardiometabolic multimorbidity in older adults with early-stage (0-3) cardiovascular-kidney-metabolic syndrome?

Key Points

To investigate whether the triglyceride-glucose index and its anthropometry-based derivatives predict incident cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic stages 0–3.
Enrolled 646 individuals without established cardiometabolic multimorbidity at baseline, categorized into CKM stages 0–3 based on AHA criteria (59% female, mean baseline age 69.42 ± 4.25 years).
Evaluated five surrogate markers of insulin resistance (TyG, TyG-CVAI, TyG-ABSI, TyG-WWI, TyG-WHtR) across five survey waves from 2021 to 2025 with a median follow-up of 4.0 years.
Assessed predictive performance and dose-response associations using Harrell's time-dependent C-statistics, net reclassification index, integrated discrimination index, and restricted cubic splines.
During the 4-year follow-up, 138 of 646 participants (21.36%) developed cardiometabolic multimorbidity, with incident cases displaying significantly higher baseline TyG and TyG-related indices (P < 0.05).
All five indices displayed significant linear dose-response associations with incident risk; in fully adjusted Model 3, TyG-WWI had the largest per-SD increase in risk (HR = 1.43, 95% CI: 1.20–1.70), followed by TyG (HR = 1.40, 95% CI: 1.19–1.63), TyG-ABSI (HR = 1.37, 95% CI: 1.16–1.60), TyG-WHtR (HR = 1.34, 95% CI: 1.13–1.60), and TyG-CVAI (HR = 1.33, 95% CI: 1.12–1.59).
TyG-WWI achieved the highest discrimination (C-index = 0.640, P < 0.001) and, alongside TyG-WHtR, demonstrated meaningful improvements in NRI and IDI compared to the TyG index alone.

Study Design

Type

Cohort (n=646)

Multicenter

No

Structured PICO

Do TyG-related indices predict incident cardiometabolic multimorbidity in older adults with early-stage (0-3) cardiovascular-kidney-metabolic syndrome?

P

Population

646 older Chinese adults (aged ≥60 years, 59% female) in early CKM stages 0-3 and free of cardiometabolic multimorbidity at baseline, followed for a median of 4.0 years.

E

Exposure

Higher levels of the triglyceride-glucose (TyG) index and four anthropometry-based TyG-derived indices (TyG-CVAI, TyG-ABSI, TyG-WWI, TyG-WHtR), evaluated as continuous variables (per standard deviation increase) and in quartiles.

C

Comparator

Lower levels (lowest quartile or reference median) of the TyG index and its related derived indices.

O

Outcome

Incident cardiometabolic multimorbidity (CMM), defined as the coexistence of two or more cardiometabolic diseases (including type 2 diabetes mellitus, coronary heart disease, and stroke) at median 4.0 years follow-up.composite

Main Result

Hazard Ratio: 1.43 (95% CI 1.2–1.7)

p-value: p=<0.001

Triglyceride-glucose related indices, particularly TyG-WWI, are independently associated with incident cardiometabolic multimorbidity and may offer clinical utility for early risk stratification in older adults across early stages of CKM syndrome.

Limitations

Observational design precludes causal inference and residual confounding or reverse causality cannot be completely excluded.
Unmeasured confounding factors such as dietary habits, medication use, and socioeconomic status.
Relatively short median follow-up of approximately four years may not capture the full progression of CMM.
CMM diagnoses were partly based on self-reported information, allowing for possible outcome misclassification.
Cohort consisted exclusively of older Chinese adults from a single region, limiting generalizability.
Overlapping components of indices caused some multicollinearity.
No direct head-to-head comparisons with established risk models.
Small number of outcome events in CKM stages 0 and 1 reduced statistical power for stage-specific analyses.
Potential confounders such as dietary intake, medication use, and socioeconomic status were not available in the study database.

Implication

TyG-WWI may support risk stratification across CKM stages 0-3; extends surrogate marker evidence but leaves open need for prospective validation.

Abstract

Cardiovascular–kidney–metabolic (CKM) syndrome is a systemic condition characterized by interrelated cardiac, renal, and metabolic disturbances. The triglyceride–glucose (TyG) index and several of its anthropometry-based derivatives have been increasingly recognized as surrogate markers of insulin resistance and potential predictors of cardiometabolic multimorbidity (CMM). However, whether their predictive performance differs across CKM stages 0–3 remains unclear. This prospective cohort investigation enrolled 646 participants without established CMM at baseline. CKM stages were classified according to AHA criteria based on obesity, metabolic abnormalities, kidney dysfunction, and subclinical cardiovascular disease. Five surrogate indicators of insulin resistance were examined, including the TyG index and four anthropometry-based TyG-derived indices. To evaluate model discrimination over time, Harrell’s time-dependent C-statistics were calculated. Improvements in predictive performance were further assessed by estimating the net reclassification index (NRI) and the integrated discrimination index (IDI). Restricted cubic spline functions were additionally fitted to depict potential dose–response relationships between each TyG-related measure and incident CMM. During a four-year follow-up, 21.36% of participants developed CMM. All TyG-related indices were significantly associated with increased CMM risk, displaying clear linear dose–response patterns. Among participants classified as CKM stage 3, TyG-WWI (TyG–weight-adjusted waist index) showed a robust association with CMM. Among all indicators, TyG-WWI and TyG-WHtR (TyG–waist-to-height ratio) showed relatively better discrimination, with meaningful improvements in NRI and IDI compared with the TyG index alone. Across CKM stages 0–3, the TyG index and its derivative markers showed consistent and independent associations with incident CMM. TyG-WWI and TyG-WHtR exhibited relatively better discrimination, highlighting their potential utility for early identification of high-risk individuals in community screening contexts, though their direct clinical applicability requires further validation.

Discussion

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Cite This Study

Chen et al. (2026) conducted a cohort in Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 (n=646). TyG-related indices (e.g., TyG-weight-adjusted waist index) vs. Reference values (lowest quartile or per standard deviation increase) was evaluated on Incident cardiometabolic multimorbidity (CMM) (HR 1.43, 95% CI 1.20-1.70, p=<0.001). A one-standard deviation increase in the TyG-weight-adjusted waist index (TyG-WWI) was associated with a 43% higher risk of incident cardiometabolic multimorbidity (HR 1.43) across CKM stages 0-3.

synapsesocial.com/papers/6ad49f5fcc23993462cc5355 https://doi.org/10.1038/s41598-026-73597-2

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Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Association of TyG-related indices with cardiometabolic multimorbidity across early cardiovascular-kidney-metabolic syndrome stages 0–3: a prospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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