Association Between Triglyceride‐Glucose Index and Risk of Gallstone Disease: A Prospective Cohort Study of 395 391 Individuals

ABSTRACT Objective Gallstone disease (GSD) is one of the widespread gastrointestinal conditions. Triglyceride‐glucose (TyG) index, a convenient surrogate for insulin resistance, may help identify and prevent gallstones. The present study aims to conduct a longitudinal study to evaluate the association between TyG index and the risk of GSD using the UK Biobank cohort. Method A total of 395 391 participants in the UK Biobank (median follow‐up of 12.52 years) were included. The association between TyG index and the risk of GSD was assessed through Cox models and the restricted cubic spline model, expressed by hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analysis was employed concerning age, gender, and body mass index (BMI) and also analyzed the mediating role of BMI in the effect of TyG index on incident GSD. Sensitivity analyses were further performed using a competing risks model and excluding participants who developed GSD in the first year of follow‐up to test the stability of the results. Results The risk of developing GSD increased in the Quartiles 2, 3, and 4 compared with Quartile 1 of TyG index (adjusted HR [aHR] 1.570 [95%CI 1.303–1.893], 1.577 [1.295–1.920], 1.489 [1.181–1.878], P trend < 0.001 across quartiles of TyG index). The aHR for every unit and SD increment in TyG index were 1.282 [1.100–1.494], 1.151 [1.055–1.256]. The results were consistent when participants who developed GSD in the first year of follow‐up were excluded. The restricted cubic spline regression also showed an increased risk of GSD with increasing TyG index. Conclusions Increased TyG index is associated with an elevated risk of GSD. The TyG index might be an important indicator for identifying people at high risk of GSD.