Abstract
OBJECTIVE: Reduced testosterone, a recognized comorbidity of reduced insulin sensitivity (IS) and type 2 diabetes (T2D), has also been reported in adult males with type 1 diabetes (T1D). However, there are limited data on how early reduced testosterone occurs, and whether it is related to the reduced IS in T1D. Leptin, a modulator of the HPG-axis, may also influence testosterone in T1D. We hypothesized that IS and leptin would be associated with total testosterone (TT), and free androgen index (FAI) in adolescent males with T1D. METHODS: T1D (n = 35), T2D (n = 13), lean (n = 13) and obese (n = 9) adolescent males had IS measured by hyperinsulinemic-euglycemic clamps (glucose infusion rate [GIR]), in addition to leptin, sex hormone binding globulin (SHBG), TT, and FAI. The cohort was stratified into those with T1D (n = 35) and those without (n = 35). RESULTS: TT and SHBG were lower in T2D boys vs. lean controls, and GIR and leptin correlated with FAI and TT in non-T1D participants. However, despite being insulin resistant, adolescent males with T1D had normal TT and FAI, unrelated to GIR. In T1D, leptin was inversely associated with TT (p = 0.005) and FAI (p = 0.01), independent of puberty, hemoglobin A1c (HbA1c), diabetes duration, body mass index (BMI) z-score and GIR. CONCLUSION: Leptin accounted for a significant proportion of the variability of testosterone in T1D. However, despite reduced IS, there was no association between IS and testosterone in T1D adolescents. These observations suggest that the mechanisms affecting testosterone may differ between adolescent males with and without T1D.