Associations of insulin resistance-related indices with the risk and progression of cardiometabolic multimorbidity in individuals with metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

Authors

Mengtong Sun, Qida He, Yu Wang, Jiazhen Yao, Yueping Shen, Zhifen Liu, Qiang Han

Published in

Cardiovascular diabetology. Jun 22, 2026. Epub Jun 22, 2026.

Abstract

Insulin resistance (IR) is thought to be a major metabolic driver of both metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic diseases (CMD). Although several IR-related indices have been linked to individual CMD, their associations with cardiometabolic multimorbidity (CMM) and stage-specific disease progression in individuals with MASLD remain unclear.
A total of 109,604 UK Biobank participants with MASLD who were free of CMD at baseline were included in this study. The analysis covered nine IR-related metrics, including the triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), TyG-body roundness index (TyG-BRI), TyG-a body shape index (TyG-ABSI), TyG-visceral adiposity index (TyG-VAI), TyG-weight-adjusted waist index (TyG-WWI), and the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C). Associations with incident CMM were estimated using Cox models. Multi-state models were applied to evaluate stage-specific transitions. Incremental predictive performance was evaluated using time-dependent ROC analyses, C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Exploratory mediation analyses were further performed to explore possible biological pathways.
Over a median follow-up of 15.9 years, 4944 participants developed CMM. Higher levels of all IR-related indices were linked to a greater risk of CMM. In the fully adjusted model, the strongest associations were observed for TyG-WHtR, TyG-BMI, and TyG-WC, with HRs (95% CIs) of 2.70 (2.45-2.97), 2.36 (2.16-2.58), and 2.33 (2.12-2.56), respectively, for the highest versus lowest quartile. Multistate analyses indicated that these indices showed stage-specific associations across the CMM trajectory. For transitions from a CMD-free state to single CMDs, the strongest associations were observed for T2D. Transitions from CHD or stroke were more likely to progress to CMM when exposed to higher IR-related indices. All indices modestly improved CMM prediction beyond conventional risk factors (all P < 0.001), with TyG-WHtR showing the best performance. Exploratory mediation analyses suggested that inflammatory, hepatic, and renal biomarkers jointly accounted for 11-23% of the associations.
Among individuals with MASLD, IR-related indices were significantly associated with the incidence and progression of CMM. Indices incorporating central adiposity, especially TyG-WHtR, provided the most informative risk estimates and modest incremental predictive value.

PMID:
42324458
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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