Triglyceride-glucose index demonstrates false-positive association with cardiometabolic multimorbidity progression in cardiometabolic disease patients: Observation and Mendelian randomization study

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiometabolic multimorbidity progression in cardiometabolic disease (n=7825). Intervention: Elevated Triglyceride-Glucose (TyG) index vs. Lower Triglyceride-Glucose (TyG) index. Primary outcome: Progression to cardiometabolic multimorbidity (CMM) (HR 0.87, 95% CI 0.73-1.02, p=0.089).

Zekai Zhou; Heng Wee Tan; Yubo Zhang; Le Yu; Yanping Wang; Songming Chen; Chujuan Zeng

doi:10.1097/md.0000000000047632

February 13, 2026MedicineOpen Access

Triglyceride-glucose index demonstrates false-positive association with cardiometabolic multimorbidity progression in cardiometabolic disease patients: Observation and Mendelian randomization study

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Key result

Elevated TyG index shows no significant association with cardiometabolic multimorbidity progression.

HR 0.87
95% CI 0.73-1.02
P=0.089
n=7,825

Figures

Why the study?

The utility of the Triglyceride-Glucose (TyG) index for predicting progression from a single cardiometabolic disease to cardiometabolic multimorbidity among patients with existing cardiometabolic disease remained unverified.

Does elevated TyG index predict progression to cardiometabolic multimorbidity in patients with existing cardiometabolic disease?

Key Points

To assess whether the triglyceride-glucose index predicts progression from a single cardiometabolic disease to cardiometabolic multimorbidity in patients with established disease.
Analyzed cross-sectional cohorts CHARLS-1 (n = 5415) and FAHSUMC (n = 544), alongside a longitudinal cohort CHARLS-2 (n = 1866).
Conducted Mendelian randomization analyses with sequential exclusion of single nucleotide polymorphisms associated with glucose, triglycerides, and body mass index to evaluate causality.
Cross-sectional models demonstrated positive associations per standard deviation increase in TyG index (CHARLS-1 adjusted OR = 1.43, 95% CI: 1.30–1.57; FAHSUMC adjusted OR = 1.75, 95% CI: 1.33–2.31).
Longitudinal cohort analysis revealed no significant association between TyG index and multimorbidity progression after multivariable adjustment (HR = 0.87, 95% CI: 0.73–1.02).

Study Design

Type

Cohort (n=7,825)

Multicenter

Yes

Structured PICO

Does elevated TyG index predict progression to cardiometabolic multimorbidity in patients with existing cardiometabolic disease?

P

Population

7,825 Chinese patients with baseline cardiometabolic diseases across three observational cohorts, analyzed alongside UK Biobank genetic data to evaluate progression to cardiometabolic multimorbidity over a median 9-year follow-up.

E

Exposure

Elevated Triglyceride-Glucose (TyG) index

C

Comparator

Lower Triglyceride-Glucose (TyG) index (tertiles Q1/Q2)

O

Outcome

Progression to cardiometabolic multimorbidity (CMM), defined as the first occurrence of CMM during follow-upcomposite

Main Result

Hazard Ratio: 0.87 (95% CI 0.73–1.02)

p-value: p=0.089

Limitations

Findings are primarily derived from Chinese cohorts, potentially limiting generalizability to other ethnic populations with different genetic backgrounds.
Possibility of residual confounding by unmeasured or imprecisely measured factors such as dietary habits, physical activity, or medication use.
Longitudinal component relied on self-reported incident CMM diagnoses, which may introduce recall or misclassification bias.
The population of Mendelian randomization studies is from the UK, which is different from the population of the observational studies.
Focused solely on the TyG index without exploring interactions or combined effects with other emerging biomarkers or risk scores.
Findings are primarily derived from Chinese cohorts, limiting generalizability to other ethnic populations.
Possibility of residual confounding by unmeasured or imprecisely measured factors.
Population of MR studies is from the UK, which is different from the population of observational studies.
Focused solely on the TyG index without exploring combined effects with other emerging biomarkers.

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Answers are grounded in this paper and cite their sources.

Implication

The TyG index is not a clinically useful biomarker for forecasting progression to cardiometabolic multimorbidity in patients with established cardiometabolic disease, as initial positive signals were likely driven by residual confounding.

Abstract

The Triglyceride-Glucose (TyG) index is a recognized predictor for incident cardiometabolic diseases (CMDs) and cardiometabolic multimorbidity (CMM) in general populations. However, its utility for predicting progression from single CMD to CMM among patients with existing CMD remains unverified. This study combined retrospective cohort analyses (cross-sectional cohorts: China Health and Retirement Longitudinal Study [CHARLS]-1, n = 5415; First Affiliated Hospital of Shantou University Medical Center, n = 544; longitudinal cohort: CHARLS-2, n = 1866) with Mendelian randomization to evaluate this relationship. Cross-sectional analyses initially indicated positive associations between elevated TyG index and CMM progression (per-standard deviation increase: CHARLS-1 adjusted odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.30–1.57; First Affiliated Hospital of Shantou University Medical Center adjusted OR = 1.75, 95% CI: 1.33–2.31). However, longitudinal analysis showed no significant association after multivariable adjustment (hazard ratio = 0.87, 95% CI: 0.73–1.02). Crucially, Mendelian randomization analysis with sequential exclusion of confounder-associated single nucleotide polymorphisms (glucose, triglycerides, and body mass index) revealed no causal relationship (Model 3 inverse-variance weighted OR = 0.647, 95% CI: 0.412–1.014). These findings demonstrate that the apparent association between TyG index and CMM progression in patients with baseline CMD is likely a false-positive result attributable to residual confounding, with no causal link supported by rigorous longitudinal or genetic evidence. Thus, while TyG is valuable for predicting initial CMD onset, it lacks clinical utility for forecasting progression to multimorbidity in established patients, necessitating exploration of alternative biomarkers for this critical transition.

Discussion

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Cite This Study

Zhou et al. (2026) conducted a cohort in Cardiometabolic multimorbidity progression in cardiometabolic disease (n=7,825). Elevated Triglyceride-Glucose (TyG) index vs. Lower Triglyceride-Glucose (TyG) index was evaluated on Progression to cardiometabolic multimorbidity (CMM) (HR 0.87, 95% CI 0.73-1.02, p=0.089). Elevated Triglyceride-Glucose index showed no significant causal association with cardiometabolic multimorbidity progression in patients with baseline cardiometabolic disease upon longitudinal multivariable adjustment (HR 0.87).

synapsesocial.com/papers/6992b4469b75e639e9b091f2 https://doi.org/10.1097/md.0000000000047632

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Triglyceride-glucose index demonstrates false-positive association with cardiometabolic multimorbidity progression in cardiometabolic disease patients: Observation and Mendelian randomization study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Triglyceride-glucose index demonstrates false-positive association with cardiometabolic multimorbidity progression in cardiometabolic disease patients: Observation and Mendelian randomization study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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