Acute and Short-term Chronic Testosterone Fluctuation Effects on Glucose Homeostasis, Insulin Sensitivity, and Adiponectin: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

作者：Host Christian; Gormsen Lars C; Hougaard David M; Christiansen Jens S; Pedersen Steen B; Gravholt Claus H^*

来源：Journal of Clinical Endocrinology & Metabolism, 2014, 99(6): E1088-E1096.

DOI：10.1210/jc.2013-2807

Context: Low levels of adiponectin and T in men have been shown to predict development of the metabolic syndrome, but the effects of T on glucose metabolism are incompletely understood and may be influenced either directly or indirectly through changes in body composition or in levels of adiponectin.
Objective: The aim of the study was to test whether T exerts its effects on glucose metabolism directly or indirectly.
Design, Setting, and Participants: In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy young males were studied on four separate occasions. They received GnRH agonist treatment 1 month before 3 of 4 trial days to induce castrate levels of T. On trial days, T gel containing either high or low physiological T dose or placebo was applied to the body. On a fourth trial day, participants constituted their own eugonadal controls.
Intervention: Each study comprised a 5-hour basal period and a 3-hour hyperinsulinemic euglycemic clamp.
Main Outcome Measures: We measured the effect of acute T on peripheral glucose disposal, total adiponectin and subforms, and other indices of glucose metabolism.
Results: Short-term hypogonadism was associated with increased high molecular weight adiponectin levels (P < .03) and increased oxidative glucose disposal (P = .03) but not total glucose disposal (P = .07). Acute T treatment was an independent suppressor of high molecular weight adiponectin levels (P = .04) but did not affect total glucose disposal (P = .17).
Conclusions: These data show that T can act through putative fast nongenomic pathways to affect adiponectin levels in humans. The early hypogonadal state is characterized by a marked shift in fuel oxidation from lipids toward glucose, which may rely partly on buffering capabilities of adiponectin.

• 出版日期2014-6