Metabolic Score for Visceral Fat and Gallstone Disease Risk: A Multicenter Cohort Study and Mediation Analysis of Inflammatory Biomarkers.

OBJECTIVES

Gallstone disease (GSD), a prevalent digestive disorder, remains mechanistically underexplored in relation to visceral adipose. The Metabolic Score for Visceral Fat (METS-VF), a novel metric for quantifying visceral adipose tissue, has not yet been evaluated for its association with GSD in cohort studies. We aimed to investigate the METS-VF-GSD association across multicenter cohorts.

METHODS

Multicenter cohort analysis of 59 851 participants from two Chinese hospitals and 357 233 participants from the UK Biobank dataset was conducted using Cox models to investigate the association between METS-VF and GSD risk. Competing risk models were also applied to the UK Biobank cohort. Meta-analysis and mediation analysis were used to synthesize results from the cohort analysis and evaluate mediation effects of inflammatory biomarkers.

RESULTS

Cox models revealed a significant positive association between METS-VF and GSD risk, with a "J-shaped" nonlinearity, as confirmed by restricted cubic spline analysis (p < 0.05). Meta-analysis revealed that for each 1-unit and 1-standard deviation increase in METS-VF, GSD risk increased by 84% and 57%, respectively. Compared with participants in quantile 1 (Q1) of METS-VF, those in Q2 (pooled hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.35-2.01), Q3 (pooled HR 2.16, 95% CI 1.83-2.54), and Q4 (pooled HR 3.00, 95% CI 2.82-3.19) were associated with progressively higher GSD risk. Mediation analysis revealed that certain inflammatory biomarkers partially mediated the effect of METS-VF on incident GSD.

CONCLUSIONS

Increased METS-VF is associated with a higher risk of GSD. It may serve as an important indicator for identifying high-risk populations for GSD.