Ducluzeau Pierre-Henri, Cousin Patrice, Malvoisin Etienne, Bornet Hubert, Vidal Hubert, Laville Martine, Pugeat Michel
Centre de Recherche en Nutrition Humaine, Hospices Civils de Lyon, 69437 Lyon Cedex 08, France.
J Clin Endocrinol Metab. 2003 Aug;88(8):3626-31. doi: 10.1210/jc.2003-030219.
Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.
多囊卵巢综合征（PCOS）是女性主要的雄激素紊乱疾病，已被认为与患心血管疾病和2型糖尿病的高风险相关。在许多PCOS患者中，超重或中心性肥胖通常与空腹胰岛素水平升高、胰岛素抵抗和葡萄糖耐量异常有关，并已被确定为新治疗策略的靶点，包括早期生活方式改变。用于识别高危患者的早期生化标志物将有助于预防研究。本研究的主要目的是寻找这样的工具。我们对16名非肥胖PCOS女性进行了正常血糖高胰岛素钳夹试验，并测量了空腹和口服葡萄糖耐量试验期间的胰岛素水平，以及血清性激素结合球蛋白（SHBG）、瘦素和脂联素（新发现的脂肪因子）的浓度。16名患者中有8名的稳态葡萄糖处置率低于8.5mg/kg·min，这是非肥胖对照女性的最低正常值。这些胰岛素抵抗患者的体重指数（BMI）和腰臀比（WHR）显著更高，高密度脂蛋白胆固醇和SHBG水平更低。正如预期的那样，葡萄糖处置与BMI（P = 0.01）、WHR（P = 0.01）和空腹胰岛素水平（P = 0.003）呈负相关。然而，在逐步回归分析中，葡萄糖-胰岛素比值（GIR）成为评估胰岛素抵抗的最强独立参数（R² = 0.61）。SHBG水平与GIR呈正相关（P < 0.001），与BMI呈负相关（P = 0.003），但与葡萄糖耐量试验期间的胰岛素反应或血浆瘦素和/或脂联素水平均无相关性。相比之下，BMI是SHBG的唯一独立预测参数（P = 0.003，R² = 0.73）。有趣的是，血浆脂联素水平与葡萄糖处置率呈正相关（P = 0.043），与WHR呈负相关（P = 0.024），腰围是脂联素水平的最佳预测指标（P < 0.01）。瘦素水平仅与BMI相关（r = 0.62，P = 0.01）。本研究证实，尽管没有肥胖，但许多PCOS女性明显存在胰岛素抵抗，并表明GIR是胰岛素抵抗最好的预测指标。还表明脂联素水平是腹部脂肪量的良好指标，且与胰岛素抵抗有关。最后，PCOS患者中低SHBG水平与BMI密切相关，提示来自脂肪组织的某些信号独立于脂联素和瘦素，可能调节肝脏SHBG的产生。
