Abate Nicola, Haffner Steven M, Garg Abhimanyu, Peshock Ronald M, Grundy Scott M
Center for Human Nutrition, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
J Clin Endocrinol Metab. 2002 Oct;87(10):4522-7. doi: 10.1210/jc.2002-020567.
Low plasma levels of SHBG and free testosterone have been associated with increased insulin resistance and risk for type 2 diabetes in males. As truncal obesity, a condition accompanied by increased insulin resistance, is also associated with low SHBG and testosterone levels, the independent association of low free testosterone and SHBG with excessive insulin resistance remains to be determined. In this study we evaluated whether in normogonadic men, plasma levels of SHBG and free testosterone are primarily related to insulin resistance or to generalized and regional adiposity. Hyperinsulinemic-euglycemic clamps and iv glucose tolerance tests were performed in 24 healthy volunteer and 33 patients with mild type 2 diabetes. The 2 groups were chosen to have similar body mass index and were found to have similar body composition and fat distribution, assessed by underwater weighing, skinfold thickness, and magnetic resonance imaging of the abdomen. In the 2 groups combined, plasma levels of SHBG correlated inversely with fat accumulation in both sc and intraabdominal areas. Plasma levels of free testosterone correlated inversely with both truncal and peripheral skinfold thickness only in the nondiabetic men. No associations between plasma levels of sex steroid hormones and insulin resistance, hepatic glucose output, or insulin secretion were found to be independent of adiposity. Furthermore, although patients with diabetes were more insulin resistant than those without diabetes, the 2 groups had similar plasma concentrations of free testosterone (55 +/- 14 and 67 +/- 27 pmol/liter, respectively), SHBG (19 +/- 13 and 19 +/- 13 nmol/liter), estradiol (83 +/- 5 and 81 +/- 21 pmol/liter), and dehydroepiandrosterone sulfate (3.6 +/- 2.2 and 2.8 +/- 1.7 nmol/liter). We conclude that in normogonadal nondiabetic males, the variability in plasma bioavailable testosterone concentrations is predictive of the variability in fat deposition in the sc adipose tissue compartments of both truncal and peripheral areas. Low plasma levels of bioavailable testosterone do not independently predict excessive insulin resistance, beta-cell dysfunction, or hepatic glucose output in normogonadal men.
血浆性激素结合球蛋白（SHBG）和游离睾酮水平低与男性胰岛素抵抗增加及2型糖尿病风险升高有关。由于腹型肥胖伴有胰岛素抵抗增加，也与SHBG和睾酮水平低有关，游离睾酮和SHBG与过度胰岛素抵抗的独立关联仍有待确定。在本研究中，我们评估了在性腺功能正常的男性中，血浆SHBG和游离睾酮水平主要是与胰岛素抵抗相关，还是与全身及局部肥胖相关。对24名健康志愿者和33名轻度2型糖尿病患者进行了高胰岛素-正常血糖钳夹试验和静脉葡萄糖耐量试验。选择这两组具有相似的体重指数，通过水下称重、皮褶厚度和腹部磁共振成像评估发现，他们具有相似的身体组成和脂肪分布。在合并的两组中，SHBG血浆水平与皮下和腹腔内区域的脂肪堆积呈负相关。仅在非糖尿病男性中，游离睾酮血浆水平与躯干和外周皮褶厚度均呈负相关。未发现性甾体激素血浆水平与胰岛素抵抗、肝葡萄糖输出或胰岛素分泌之间的关联独立于肥胖。此外，尽管糖尿病患者比非糖尿病患者的胰岛素抵抗更强，但两组的游离睾酮（分别为55±14和67±27 pmol/升）、SHBG（19±13和19±13 nmol/升）、雌二醇（83±5和81±21 pmol/升）和硫酸脱氢表雄酮（3.6±2.2和2.8±1.7 nmol/升）血浆浓度相似。我们得出结论，在性腺功能正常的非糖尿病男性中，血浆生物可利用睾酮浓度的变异性可预测躯干和外周区域皮下脂肪组织隔室中脂肪沉积的变异性。性腺功能正常男性的低血浆生物可利用睾酮水平并不能独立预测过度胰岛素抵抗、β细胞功能障碍或肝葡萄糖输出。
