Effects of the triglyceride-glucose index on non-alcoholic fatty liver disease: Causal evidence from longitudinal cohort studies.

Background: Insulin resistance (IR) is strongly related to non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index serves as a novel substitute indicator for IR. However, research on the effect of TyG index on NAFLD remains sparse. This study aims to investigate the causal association between TyG index and incident NAFLD.

Methods: The primary cohort consisted of 27,052 participants from the Beijing Health Management Cohort, while the external validation cohort included 75,023 participants from the Taiwan MJ Cohort. Entropy balancing for continuous treatments (EBCT) combined with logistic regression and targeted maximum likelihood estimation (TMLE) were used to evaluate the causal association between the TyG index and incident NAFLD.

Results: During a median follow-up of 2.49 years in the primary cohort, 6,168 participants (median age: 36.0 years) developed incident NAFLD. EBCT combined with logistic regression revealed the odds ratio (95 % CI) of NAFLD risk was 1.742 (1.478-2.054) for each 1-unit increase in the baseline TyG index. In the TMLE model, the risk ratio (95 % CI) for NAFLD was 1.540 (1.406-1.687) in the Q4 (quartile 4) group compared with the Q1 group. These findings were consistent with those from the external validation cohort, reinforcing the robustness of the causal relationship between the TyG index and NAFLD incidence.

Conclusions: The advanced double-robust estimation method suggests that a higher baseline TyG index may be causally associated with an increased NAFLD risk, providing more reliable evidence for its role as a simple biomarker and demonstrating the utility of double-robust estimation causal inference models in epidemiology.