Gamma-Glutamyl Transferase and Male Reproductive Hormone Levels in Men with Type 2 Diabetes: A Cross-Sectional Study

Introduction: Although Gamma-Glutamyl Transferase (GGT) has been implicated in metabolic disorders, its association with male reproductive hormones in type 2 diabetes mellitus (T2DM) remains unclear. Methods: In this cross-sectional study, 971 men with T2DM were recruited from Shandong Provincial Hospital. Serum GGT levels were measured as the primary exposure variable, while male reproductive hormones—including total testosterone (TT), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG)—served as outcome variables. Multivariable linear regression, threshold effect models, and subgroup analyses were used to assess associations, adjusting for age, BMI, glycemic control, and other confounders. Results: The mean age of participants was 56.37 ± 12.49 years. After full adjustment, men in the highest GGT tertile exhibited a 0.44 ng/mL reduction in TT levels compared to the lowest tertile (P < 0.01). A nonlinear relationship was identified, with a saturation effect at GGT = 118 IU/L. Below this threshold, each 10-IU/L increase in GGT corresponded to a 0.13 ng/mL decrease in TT (95% CI: −0.21 to −0.05). Unadjusted inverse associations with SHBG (β=-14.87, 95%CI:-26.47 to -3.28) and LH (β=-1.34, 95%CI:-2.14 to -0.54) became nonsignificant after adjustment (P>0.05). No FSH associations were detected. Discussion: Our findings reveal a novel dose-dependent relationship between GGT and testosterone in T2DM, with effects plateauing beyond 118 IU/L. This threshold may reflect the point where oxidative stress overwhelms gonadal compensatory mechanisms. Conclusion: The nonlinear relationship suggests GGT may help identify androgen deficiency risk, though SHBG/LH links appear confounder-dependent. Monitoring GGT could aid T2DM male health management.