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Background <p>Insulin resistance and muscle loss are interrelated processes linked to cardiovascular disease (CVD), but they are rarely assessed together. We investigated the association between a novel integrated biomarker—triglyceride–glucose muscle-loss index (TyG–MLI)—and incident CVD in a large prospective cohort.</p> Methods <p>A total of 277,418 UK Biobank participants free of CVD at baseline were included. TyG–MLI was calculated as ln[(triglycerides × fasting glucose)/2] × (cystatin C/creatinine). Incident CVD was identified through hospital admissions and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).</p> Results <p>Over a median follow-up of 15.1&#xa0;years, 40,398 participants developed CVD. Crude CVD incidence increased steadily across TyG–MLI quartiles, and the cumulative incidence curves demonstrated clear separation on Kaplan–Meier analysis (log-rank <i>p</i> &lt; 0.001). Higher TyG–MLI was independently associated with greater CVD risk when modeled either continuously (per 1-SD: HR 1.17; 95% CI 1.16–1.18) or categorically (Q4 vs. Q1: HR 1.48; 95% CI 1.44–1.53). Restricted cubic spline analyses demonstrated a non-linear association across the TyG–MLI distribution. Sensitivity analyses yielded consistent results. In body mass index-stratified analyses, TyG–MLI showed stronger associations with CVD than TyG index, particularly among normal-weight and underweight individuals.</p> Conclusions <p>TyG–MLI, a composite marker reflecting insulin resistance and muscle loss, was independently associated with incident CVD in this large population-based cohort. These findings suggest that TyG–MLI captures cardiometabolic risk beyond traditional measures and may be particularly informative in individuals without obesity.</p> Graphical abstract <p></p>

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Association between triglyceride–glucose muscle-loss index (TyG–MLI) and incident cardiovascular disease: a prospective cohort study in the UK biobank

  • 期刊论文

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  • 发表日期：

    2025年12月13日

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  • Yanwen Fang,
  • Sizhuang Huang,
  • Hao Zhang,
  • Mingyang Li,
  • Haihua Zhang,
  • Weixian Yang,
  • Mengyue Yu

摘要

Background

Insulin resistance and muscle loss are interrelated processes linked to cardiovascular disease (CVD), but they are rarely assessed together. We investigated the association between a novel integrated biomarker—triglyceride–glucose muscle-loss index (TyG–MLI)—and incident CVD in a large prospective cohort.

Methods

A total of 277,418 UK Biobank participants free of CVD at baseline were included. TyG–MLI was calculated as ln[(triglycerides × fasting glucose)/2] × (cystatin C/creatinine). Incident CVD was identified through hospital admissions and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Over a median follow-up of 15.1 years, 40,398 participants developed CVD. Crude CVD incidence increased steadily across TyG–MLI quartiles, and the cumulative incidence curves demonstrated clear separation on Kaplan–Meier analysis (log-rank p < 0.001). Higher TyG–MLI was independently associated with greater CVD risk when modeled either continuously (per 1-SD: HR 1.17; 95% CI 1.16–1.18) or categorically (Q4 vs. Q1: HR 1.48; 95% CI 1.44–1.53). Restricted cubic spline analyses demonstrated a non-linear association across the TyG–MLI distribution. Sensitivity analyses yielded consistent results. In body mass index-stratified analyses, TyG–MLI showed stronger associations with CVD than TyG index, particularly among normal-weight and underweight individuals.

Conclusions

TyG–MLI, a composite marker reflecting insulin resistance and muscle loss, was independently associated with incident CVD in this large population-based cohort. These findings suggest that TyG–MLI captures cardiometabolic risk beyond traditional measures and may be particularly informative in individuals without obesity.

Graphical abstract