Abstract
BACKGROUND: Emerging evidence suggests that insulin sensitivity plays a role in testosterone regulation. The estimated glucose disposal rate (eGDR) is a validated metabolic marker reflecting insulin resistance (IR). However, the relationship between eGDR and testosterone levels in adult men remains unclear. AIM: This study aimed to examine the association between eGDR, total testosterone (TT) levels, and testosterone deficiency (TD) risk. METHODS: Data from the 2013-2016 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted multivariable linear and logistic regression models were used to evaluate the association between eGDR, TT levels, and TD risk (TT <300 ng/dL). A smoothing spline curve fitting approach was applied to assess the shape of the relationship. Subgroup analyses and interaction tests were conducted to explore potential effect modifications. Receiver operating characteristic (ROC) analysis was performed to assess the predictive ability of eGDR for TD. OUTCOMES: eGDR was calculated using waist circumference (WC), hypertension (HTN), and glycated hemoglobin (HbA1c). RESULTS: A total of 4087 male participants were included in the final analysis. After adjusting for all covariates, higher eGDR was significantly associated with increased TT levels (β = 31.83, 95% CI, 22.13-41.54, P < .001) and a lower risk of TD (OR = 0.68, 95% CI, 0.58-0.80, P = .002). Quartile analysis showed that participants in the highest eGDR quartile (Q4) had significantly higher TT levels than those in Q1 (β = 147.27, 95% CI, 66.99-227.55, P = .02) and a markedly reduced TD risk (OR = 0.20, 95% CI, 0.06-0.70, P = .03). Smoothing spline curve fitting approach confirmed a linear relationship between eGDR and TT levels, as well as an inverse association with TD risk. A significant interaction was observed for diabetes status (P for interaction = .001), indicating a potential modifying effect. ROC analysis demonstrated that eGDR had moderate predictive ability for TD (AUC = 0.6839, 95% CI, 0.6659-0.7019). CLINICAL IMPLICATIONS: eGDR may serve as a useful metabolic marker for identifying individuals at risk of TD. STRENGTHS AND LIMITATIONS: GDR may serve as a valuable metabolic marker for identifying individuals at risk of TD; due to its cross-sectional design, we cannot establish causality between eGDR and testosterone levels. CONCLUSION: These findings suggest that eGDR is associated with testosterone levels and TD risk in adult men, highlighting the potential metabolic link between insulin sensitivity and testosterone regulation.