FP33-5 Leptin, insulin resistance and testosterone in young males with T1D: evidence for an association between testosterone and leptin

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP33-Insulin Signaling & Inflammation
Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 303 (Moscone Center)

Poster Board MON-847
Petter Bjornstad*1, Megan Moriarty Kelsey2, Kim McFann3 and Kristen Jane Nadeau2
1Children's Hospital Colorado / University of Colorado Anschutz Medical Campus, CO, 2Children's Hospital Colorado, Aurora, CO, 3University of Colorado, Denver, Aurora, CO
Gonadal dysfunction is a known complication of insulin resistance (IR) and type 2 diabetes (T2D) in both males and females. However, there are limited data on the incidence of and mechanisms for hypogonadism in young males with type 1 diabetes (T1D), who also have well-documented IR as a component of their disease. IR, which has been shown to be negatively associated with testosterone in males with T2D, and leptin, a recognized modulator of HPG axis, are both plausible contributors to gonadal dysfunction in males with T1D. We assessed the relationships among insulin sensitivity (IS), leptin and both free and total testosterone levels in males with T1D.

T1D (n=34), T2D (n=13) and lean (n=12) males had IS measured by hyperinsulinemic-euglycemic clamp (expressed as M-value). Other measures included leptin, testosterone, and sex hormone binding globulin. Free androgen index (FAI) was calculated using a modified Vermeuelen-equation.

Total testosterone was not different between T1D and lean males (p = 0.729), but was lower in T2D (p < 0.01). Both T1D (p < 0.01) and T2D (p < 0.01) subjects were more IR than lean controls, and those with T2D were more IR than T1D (p < 0.01). Leptin was negatively associated with both FAI (β±SE: -21±8, p = 0.038) and total testosterone (β±SE: -108±31, p = 0.002) in T1D subjects, adjusting for Tanner stage. Leptin accounted for 19% of the variability in testosterone in T1D males (p = 0.011). In a multivariate model including Tanner stage, HbA1c, diabetes duration, BMI Z-score, M-value and Lnleptin, only leptin was associated with testosterone (p = 0.008). In a multivariate model including Tanner stage, group and Lnleptin, only leptin was associated with testosterone (β±SE = -93 ± 27, p = 0.001), and after adjustment for leptin, group differences in testosterone were no longer significant (β±SE = Type 1: 344±33, Type II: 248±75, and Lean: 224±68, p = 0.177). No relationship between M-value and FAI (p = 0.932) or total testosterone (p = 0.728) was found in T1D.

In conclusion, leptin was negatively associated with both free and total testosterone in T1D, and accounted for a portion of the testosterone variability among T1D males. In contrast to previous findings in T1D, T1D males in this cohort were not hypogonadal. Furthermore, in contrast to obese and T2D adolescent males, IR was not associated with testosterone in T1D males. These observations emphasize the importance of leptin in gonadal function and raise the possibility that relationships among IR, leptin and testosterone may differ in T1D and T2D.

Nothing to Disclose: PB, MMK, KM, KJN

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