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评估 2 型糖尿病的正常生育男性的下丘脑-垂体-性腺轴。

Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus.

机构信息

Endocrinology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

出版信息

Andrology. 2014 Jan;2(1):117-24. doi: 10.1111/j.2047-2927.2013.00163.x. Epub 2013 Nov 26.

DOI:10.1111/j.2047-2927.2013.00163.x
PMID:24282162
Abstract

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10 min for 4 h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90 min after 100 μg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72 h post 5000 IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1 ± 25.5 vs. 99.1 ± 13.6 mg/dL, p = 0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8 ± 0.8 vs. 1.5 ± 0.5 pulses, p = 0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p = 0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.

摘要

患有 2 型糖尿病(DM2)的男性睾丸酮水平较低,性腺功能减退症的患病率较高。目前仍不清楚性腺功能减退症与 DM2 之间存在关联的机制。本研究旨在评估 DM2 患者不同水平的下丘脑-垂体-性腺轴。将 14 名 DM2 患者(DM2 组)和 15 名无 DM2 的受试者(正常糖耐量试验)作为对照组(CG)纳入研究。我们评估了:(i)空腹血糖、胰岛素、稳态模型评估(HOMA);(ii)通过每 10 分钟采集一次血样,连续采集 4 小时,以评估黄体生成素(LH)脉冲;(iii)促性腺激素释放激素(GnRH)试验:基础 LH 和静脉注射 100μg GnRH 后 30、60 和 90 分钟的 LH;(iv)人绒毛膜促性腺激素(hCG)试验:基础总睾酮(TT)、生物可利用睾酮(BT)、游离睾酮(FT)、雌二醇(E2)、生物可利用 E2(BE2)和性激素结合球蛋白(SHBG),以及肌肉注射 5000IU hCG 后 72 小时的 TT、BT、FT、E2、BE2 和 SHBG。两组间的年龄、体重指数和腰围均无差异。DM2 组的血糖水平高于 CG 组:131.1±25.5 vs. 99.1±13.6mg/dL,p=0.0005。两组间的基础胰岛素、HOMA、TT、BT、FT、E2、BE2、SHBG 和 LH 水平均无差异。DM2 组的 LH 脉冲频率低于 CG 组:0.8±0.8 vs. 1.5±0.5 脉冲,p=0.009。LH 脉冲幅度无差异。LH 脉冲数与血糖呈负相关,r:-0.39,p=0.03。两组间 GnRH 对 LH 的反应以及 hCG 对性激素和 SHBG 的反应均无差异。DM2 患者下丘脑脉冲频率降低,而 GnRH 对垂体的反应和 hCG 对睾丸的反应均无变化。血糖水平与 LH 脉冲数呈负相关,提示高血糖对 GnRH 下丘脑分泌有负面影响。

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