Yanyan Xuan, Jingbo Yu, Qi Yao
In non-diabetic Japanese adults, TyHGB is independently and non-linearly associated with MASLD, with WC partially mediating this relationship. The marked attenuation of WC mediation among obese individuals suggests a relative shift towards non-WC-mediated pathways under high metabolic burden. TyHGB may serve as a practical composite surrogate marker for MASLD risk stratification in community settings, particularly for non-obese individuals in whom WC captures a larger share of the risk pathway and who are frequently missed by BMI-based assessment.
BACKGROUND: The triglyceride high-density cholesterol-glucose body index (TyHGB) integrates atherogenic dyslipidemia, glucose metabolism, and generalized obesity, aligning closely with the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, whether its association with MASLD follows a non-linear pattern and to what extent waist circumference (WC)-a surrogate for visceral adiposity-mediates this relationship remains unclear.
METHODS: This cross-sectional study included 13,682 non-diabetic Japanese adults from a community-based cohort. Multivariable logistic regression, generalized additive models, and two-piecewise linear regression were used to evaluate the independent and non-linear association between TyHGB and prevalent MASLD. Mediation analysis with 1,000 bootstrap resamples quantified the mediating effect of WC and its heterogeneity across metabolic subgroups.
RESULTS: The overall prevalence of MASLD was 15.25%. Each 1-unit increase in TyHGB was associated with a 1.35-fold higher odds of MASLD (OR = 1.35, 95% CI: 1.31-1.40, P < 0.001). A non-linear inflection point was identified at TyHGB = 9.70; below this threshold, the association was markedly stronger (OR=2.02, 95% CI: 1.88-2.17), whereas above it the risk increment plateaued (OR = 1.04, P = 0.090). WC partially mediated 46.4% of the TyHGB-MASLD association, with a substantially larger mediated proportion in non-obese individuals (42.67%) than in obese participants (7.83%).
CONCLUSION: In non-diabetic Japanese adults, TyHGB is independently and non-linearly associated with MASLD, with WC partially mediating this relationship. The marked attenuation of WC mediation among obese individuals suggests a relative shift towards non-WC-mediated pathways under high metabolic burden. TyHGB may serve as a practical composite surrogate marker for MASLD risk stratification in community settings, particularly for non-obese individuals in whom WC captures a larger share of the risk pathway and who are frequently missed by BMI-based assessment.