Tsai Elaine C, Matsumoto Alvin M, Fujimoto Wilfred Y, Boyko Edward J
Veterans Affairs Puget Sound Health Care System and the University of Washington, Seattle, Washington 98108, USA.
Diabetes Care. 2004 Apr;27(4):861-8. doi: 10.2337/diacare.27.4.861.
Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men.
Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]).
Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P < 0.0001], and -0.38 [P < 0.0001], respectively), fasting C-peptide (r = -0.18 [P = 0.009] to -0.41 [P < 0.0001]), HOMA-IR (r = -0.15 [P = 0.03] to - 0.39 [P < 0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG.
The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.
先前关于低睾酮水平与糖尿病风险之间关联的报告常因性激素结合球蛋白（SHBG）和睾酮测量值的共变而混淆。本研究检测了生物可利用睾酮和游离睾酮（更可靠的生物活性睾酮指标）与221名中年非糖尿病男性胰岛素抵抗标志物及体脂测量值之间的关联。
根据总睾酮、SHBG和白蛋白浓度计算生物可利用睾酮和游离睾酮，它们与SHBG无显著相关性（r = 0.07 - 0.1）。相比之下，总睾酮与SHBG显著相关（r = 0.63）。我们评估了这些循环睾酮指标与胰岛素抵抗标志物（即空腹胰岛素、C肽和胰岛素抵抗稳态模型评估[HOMA-IR]）以及总体脂（通过双能X线吸收法[DEXA]评估）和腹部脂肪分布（通过单层计算机断层扫描[CT]评估）之间的关系。
生物可利用睾酮、游离睾酮、总睾酮和SHBG均与空腹胰岛素显著相关（年龄校正r分别为 -0.15 [P = 0.03]、-0.14 [P = 0.03]、-0.32 [P < 0.0001]和 -0.38 [P < 0.0001]），与空腹C肽（r = -0.18 [P = 0.009]至 -0.41 [P < 0.0001]）、HOMA-IR（r = -0.15 [P = 0.03]至 -0.39 [P < 0.0001]）以及体脂测量值（r = -0.17 [P = 0.008]至 -0.44 [P < 0.0001]）也显著相关。仅SHBG和总睾酮与空腹血糖显著相关（r = -0.20 [P = 0.003]至 -0.21 [P = 0.002]）。在多变量分析中，生物可利用睾酮或游离睾酮与胰岛素、C肽和HOMA-IR显著负相关，但这并非独立于总体脂或腹部脂肪。SHBG是胰岛素、C肽和HOMA-IR的显著决定因素，独立于体脂。总睾酮与胰岛素抵抗之间的关联因SHBG而混淆。
睾酮与胰岛素抵抗之间的负相关独立于SHBG，是通过体脂介导的。
