Abstract
BACKGROUND: Both anti-aging protein α-Klotho and the triglyceride-glucose (TyG) index hold predictive value for the incidence, progression, and outcomes of cardiovascular disease, diabetes and many other diseases. However, their relationship remains unclear. METHODS: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Weighted multivariate linear regression models and subgroup analysis were constructed to assess the association between TyG index and α-Klotho levels. Nonlinear correlations were explored using restricted cubic splines (RCS), generalized additive models (GAM) and smooth curve fitting. Segmented regression model was conducted to explore potential threshold effects and identify the inflection point. RESULTS: A total of 2568 participants satisfied the predetermined criteria were enrolled in the final analysis. After fully adjusting for covariates, TyG index was shown to be markedly negatively correlated with α-Klotho [β=-74.07, 95%CI (-100.29,-47.85), p < 0.001]. Gender was significantly correlated with this negative connection according to subgroup analysis and interaction testing (p for interaction < 0.05).Additionally, we discovered a linear association between TyG index and α-Klotho in all participants (p for nonlinear = 0.761), while non-linear association in female (p for nonlinear = 0.016).The analysis of threshold effect in the female participants found that the inflection point of TyG index was 8.01, exceed which the level of α-Klotho decreased significantly with increasing TyG index[β=-151.72, 95%CI (-201.93, -101.50), p < 0.001]. CONCLUSION: Our findings demonstrate a negative association between TyG index and α-Klotho levels, with the effect being more pronounced in females. TyG index may serve as an early indicator of individuals with low α-Klotho levels, especially among females. These findings highlight the need for gender-specific considerations in clinical interventions to improve public health. Further research is needed to clarify the causal direction of this association.