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Triglyceride-Glucose Index, Genetic Susceptibility, and the Risk of Kidney Stone Disease: A Prospective Cohort Study
33 Pages Posted: 7 May 2025
More...Abstract
Background: Longtitudinal evidence about the association of triglyceride-glucose (TyG) index with kidney stone disease (KSD) is limited. We aimed to assess the associations between TyG, genetic risk, and the risk of KSD, as well as identify the optimal among the modified TyG indices combining obesity parameters.
Methods: The cohort analyses included 413,209 participants free of KSD from the UK Biobank. Cox proportional hazards models were used to evaluate the associations between the TyG indices and the incidence of KSD. The time-dependent C-index was used to evaluate the predictive performance. Moreover, we constructed a polygenic risk score (PRS) using KSD-associated variants and examined its potential interaction with TyG indices on KSD risk.
Results: Over a median follow-up of 12.7 years, 4,551 participants developed KSD. The incidence of KSD increased progressively with elevated levels of all TyG indices. Compared with the lowest tertile, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of KSD in the highest tertile for TyG, TyG-BMI (body mass index [BMI]), TyG-WC (waist circumference [WC]), and TyG-WHtR (waist-to-height ratio [WHtR]) were 1.37 (1.27, 1.48), 1.58 (1.46, 1.71), 1.80 (1.65, 1.97), and 1.78 (1.64, 1.94), respectively. Among these indices, TyG-WC demonstrated the strongest predictive performance (c-index = 0.625, 95% CI = 0.617–0.633). No significant interaction was observed between TyG indices and genetic susceptibility.
Conculusion: TyG indices were positively associated with the risk of KSD irrespective of genetic predisposition. Among the modified TyG indices, TyG-WC demonstrated the highest diagnostic effectiveness for KSD.
Keywords: Triglyceride Glucose Index, Kidney Stone Disease, Genetic Susceptibility, Cohort Study
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