Lee Chien-Hsing, Kuo Shi-Wen, Hung Yi-Jen, Hsieh Chang-Hsun, He Chih-Tsueng, Yang Tsao-Chin, Lian Wei-Cheng, Chyi-Fan Sandra, Pei Dee
Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Endocr Res. 2005;31(2):139-48. doi: 10.1080/07435800500320653.
Our understanding of the effect of androgens on insulin action and glucose metabolism is incomplete. Several different models and methods have been used to study androgen effects, with some studies indicating that higher testosterone levels are associated with increased insulin resistance. In polycystic ovary syndrome, where high testosterone levels are frequently found, affected patients have a higher risk of diabetes. In contrast, increased insulin resistance was found in both hypergonadotropic and hypogonadotropic men with hypoandrogenism, patients with Klinefelter's syndrome and men with idiopathic gonadotropin deficiency. Insulin resistance is considered to be one of the cornerstones in the state that ultimately leads to clinically established type 2 diabetes mellitus. In addition, men with type 2 diabetes have relative hypogonadism. Therefore, supplementation with testosterone might play a role in improving both insulin resistance and hypogonadism. The study population consisted of 11 male patients with type 2 diabetes. Their mean age was 57.7 +/- 3.41 years, the body mass index (BMI) was 24.4 +/- 1.02 kg/m2, and the waist-to-hip ratio (W/H) was 0.91 +/- 0.05. The patients were all treated with oral hypoglycemic agents. The men received androgen injections every 3 weeks intramuscularly for 12 weeks. The injections were testosterone depot 100 mg/3 weeks. Insulin sensitivity, glucose effectiveness and area under acute insulin response were calculated from "minimal model" algorithms. There were no significant differences in the value of BMI, W/H ratios, plasma lipid concentrations, testosterone, homeostasis model assessment (HOMA) of insulin sensitivity, and beta-cell function, before and after supplementation of testosterone. Furthermore, the insulin sensitivity (SI) (1.04 +/- 0.25, 1.11 +/- 0.36 x 10(-5) min(-1/)pM; p = 0.43), glucose effectiveness (EG) (0.018 +/- 0.003, 0.017 +/- 0.002 min(-1); p = 0.29), and acute insulin response (AIR) after a glucose load (45.7 +/- 24.3, 50.1 +/- 32.5 pM; p = 0.45) did not change significantly after supplmentation with testosterone. In our study, there was no improvement of SI, EG, and AIR after 3 months of Testosterone Depot treatment in type 2 diabetes, but we believe that duration and dosage of the androgen therapy might play an important role in improving insulin sensitivity. The mechanisms by which testosterone causes insulin resistance is unknown, and larger studies on androgen treatment in type 2 diabetic patients are necessary.
我们对雄激素对胰岛素作用及葡萄糖代谢的影响的理解并不完整。已采用多种不同模型和方法来研究雄激素的作用，一些研究表明较高的睾酮水平与胰岛素抵抗增加有关。在多囊卵巢综合征患者中，经常发现其睾酮水平较高，这些患者患糖尿病的风险更高。相比之下，在高促性腺激素性和低促性腺激素性性腺功能减退的男性、克兰费尔特综合征患者以及特发性促性腺激素缺乏的男性中均发现了胰岛素抵抗增加。胰岛素抵抗被认为是最终导致临床确诊的2型糖尿病状态的基石之一。此外，2型糖尿病男性存在相对性腺功能减退。因此，补充睾酮可能在改善胰岛素抵抗和性腺功能减退方面发挥作用。研究人群包括11名2型糖尿病男性患者。他们的平均年龄为57.7±3.41岁，体重指数（BMI）为24.4±1.02kg/m²，腰臀比（W/H）为0.91±0.05。所有患者均接受口服降糖药治疗。这些男性每3周接受一次睾酮肌肉注射，共12周。注射药物为长效睾酮100mg/3周。根据“最小模型”算法计算胰岛素敏感性、葡萄糖效能和急性胰岛素反应曲线下面积。补充睾酮前后，BMI值、W/H比值、血脂浓度、睾酮、胰岛素敏感性的稳态模型评估（HOMA）以及β细胞功能均无显著差异。此外，补充睾酮后，胰岛素敏感性（SI）（1.04±0.25，1.11±0.36×10⁻⁵min⁻¹/pM；p = 0.43）、葡萄糖效能（EG）（0.018±0.003，0.017±0.002min⁻¹；p = 0.29）以及葡萄糖负荷后的急性胰岛素反应（AIR）（45.7±24.3，50.1±32.5pM；p = 0.45）均无显著变化。在我们的研究中，2型糖尿病患者接受长效睾酮治疗3个月后，SI、EG和AIR并未改善，但我们认为雄激素治疗的持续时间和剂量可能在改善胰岛素敏感性方面发挥重要作用。睾酮导致胰岛素抵抗的机制尚不清楚，有必要对2型糖尿病患者进行更大规模的雄激素治疗研究。
