Association of cumulative triglyceride-glucose index with incident metabolic dysfunction-associated steatotic liver disease: a cohort study
S Kang, N Zhang, W Chen, Y Chen, Z Li, W Li, R HuangAbstract
Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global public health burden with progressive hepatic and cardiometabolic consequences. Insulin resistance is central to MASLD pathogenesis, and the triglyceride-glucose (TyG) index is a practical surrogate marker for insulin resistance that has been associated with MASLD risk across populations. However, most studies rely on cross-sectional or single baseline measurements, limiting assessment of long-term metabolic exposure. Using a large community-based prospective cohort, this study investigates whether cumulative TyG exposure better predicts incident MASLD and supports earlier risk identification and dynamic risk stratification.
Objective
Leveraging a large community-based prospective cohort, this study aims to comprehensively evaluate the longitudinal association between cumulative exposure to the TyG index and the risk of incident MASLD. By quantifying the cumulative TyG burden over time, we seek to deepen the understanding of how insulin resistance-related metabolic dysregulation contributes to MASLD progression.
Methods
Time-weighted cumulative TyG index (cumTyG) was calculated using three consecutive annual measurements from 2016 to 2018 for 2,203 eligible participants. To examine the association between cumTyG and the risk of incident MASLD, we performed multivariable Cox proportional hazards regression analyses and sequentially constructed three progressively adjusted models. To further explore potential modifiers, subgroup analyses were conducted according to age, sex, smoking status, alcohol consumption, educational attainment, marital status, BMI, hypertension status, and diabetes status to evaluate possible effect modification.
Results
During a median follow-up of 39 months, 1,009 incident cases of MASLD were identified. After adjustment for potential confounders, each 1-unit increase in cumTyG was associated with an increased risk of incident MASLD (hazard ratio [HR], 2.22; 95% CI, 1.78-2.76). Compared with the lowest quartile, individuals in the highest cumTyG quartile had a significantly elevated risk of MASLD (HR, 2.33; 95% CI, 1.80-3.02; P for trend < .001, Figure 1). Subgroup analyses showed no significant interactions in the association between cumTyG and MASLD across strata defined by sex, age, BMI, smoking history, alcohol consumption, hypertension, or diabetes (Figure 2).
Conclusion
Cumulative exposure to an elevated TyG index is independently associated with an increased risk of incident MASLD. Dynamic assessment of the TyG index over time offers superior prognostic value for early risk stratification compared with a single measurement.Figure 1Figure 2