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

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.

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.

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.

Our findings reveal a novel dose-dependent relationship between GGT and TT in T2DM, with effects plateauing beyond 118 IU/L. This threshold may reflect the point where oxidative stress overwhelms gonadal compensatory mechanisms.

The nonlinear relationship between GGT and TT suggests GGT may help identify androgen deficiency risk in T2DM though SHBG/LH links appear confounder-dependent. Monitoring GGT could aid T2DM male health management.