Legro R S, Finegood D, Dunaif A
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
J Clin Endocrinol Metab. 1998 Aug;83(8):2694-8. doi: 10.1210/jcem.83.8.5054.
Women with polycystic ovary syndrome (PCOS) are profoundly insulin resistant, and the resultant hyperinsulinemia exacerbates the reproductive abnormalities of the syndrome. Agents that ameliorate insulin resistance and reduce circulating insulin levels could provide a new therapeutic modality for PCOS. Identifying the subset of PCOS women who are most insulin resistant may therefore be useful for selecting women who will respond to this therapy. We examined the correlation of basal and oral glucose-stimulated glucose and insulin levels and fasting and stimulated glucose/insulin (G:I) ratios with parameters of insulin sensitivity obtained by frequently sampled i.v. glucose tolerance test (FSIGT) to assess whether there is a simple screening test for insulin resistance in PCOS. Forty PCOS women (aged 18-40 yr; body mass index, >26 kg/m2) and 15 control women matched for age, weight, and ethnicity underwent both a 75-g oral glucose tolerance test (OGTT) and a FSIGT. The insulin sensitivity index (S(I)) was calculated by application of the minimal model of glucose kinetics to the dynamics of plasma glucose and insulin levels during the FSIGT. The best correlation in PCOS between S(I) and a fasting level was found with fasting G:I ratios (r = 0.73; P < 0.0001). A less substantial, but significant, correlation was found with fasting insulin levels (r = 0.50; P < 0.001), and no significant correlation was found with fasting glucose levels (r = 0.24; P = NS). The fasting G:I was more strongly correlated with S(I) than with integrated glucose and insulin responses during the OGTT. The only stronger correlation was with the OGTT 2 h G:I ratio (r = 0.74; P < 0.001). Stepwise regression analysis with S(I) as the dependent variable and fasting glucose and insulin levels, area under the curve for glucose and insulin, and a fasting G:I ratio showed that only the fasting G:I ratio was significantly predictive of S(I) in the model (F to remove value = 38.1; P < 0.001). When viewed as a screening test for insulin resistance in PCOS, setting a value of the fasting G:I ratio of less than 4.5 as abnormal (using an S(I) value below the 10th percentile of our control population as evidence for insulin resistance), the sensitivity of a fasting G:I ratio was 95%, the specificity was 84%, the positive predictive value was 87%, and the negative predictive value was 94%. Receiver operator curve analysis showed that this fasting G:I ratio was the single best screening measure for detecting insulin resistance. We conclude that a fasting G:I ratio may be useful as a screening test for insulin resistance in obese non-Hispanic white PCOS women. This may be a clinically useful parameter for selecting PCOS women most likely to respond to therapeutic interventions that improve insulin sensitivity.
患有多囊卵巢综合征(PCOS)的女性存在严重的胰岛素抵抗,由此产生的高胰岛素血症会加剧该综合征的生殖异常。改善胰岛素抵抗并降低循环胰岛素水平的药物可为PCOS提供一种新的治疗方式。因此,识别出胰岛素抵抗最严重的PCOS女性亚组,可能有助于选择对这种治疗有反应的女性。我们研究了基础及口服葡萄糖刺激后的血糖和胰岛素水平、空腹及刺激后的葡萄糖/胰岛素(G:I)比值与通过频繁采样静脉葡萄糖耐量试验(FSIGT)获得的胰岛素敏感性参数之间的相关性,以评估是否存在一种简单的PCOS胰岛素抵抗筛查试验。40名PCOS女性(年龄18 - 40岁;体重指数,>26 kg/m²)和15名年龄、体重及种族匹配的对照女性接受了75 g口服葡萄糖耐量试验(OGTT)和FSIGT。胰岛素敏感性指数(S(I))通过将葡萄糖动力学最小模型应用于FSIGT期间血浆葡萄糖和胰岛素水平的动态变化来计算。在PCOS中,发现S(I)与空腹水平之间的最佳相关性存在于空腹G:I比值(r = 0.73;P < 0.0001)。与空腹胰岛素水平存在较弱但显著的相关性(r = 0.50;P < 0.001),与空腹血糖水平无显著相关性(r = 0.24;P = 无显著性差异)。空腹G:I与S(I)的相关性比与OGTT期间葡萄糖和胰岛素的综合反应更强。唯一更强的相关性是与OGTT 2小时G:I比值(r = 0.74;P < 0.001)。以S(I)为因变量,空腹血糖和胰岛素水平、葡萄糖和胰岛素曲线下面积以及空腹G:I比值进行逐步回归分析,结果显示在模型中只有空腹G:I比值能显著预测S(I)(剔除值的F = 38.1;P < 0.001)。当将空腹G:I比值视为PCOS胰岛素抵抗的筛查试验时,将空腹G:I比值设定为低于4.5为异常(使用低于我们对照人群第10百分位数的值作为胰岛素抵抗的证据),空腹G:I比值的敏感性为95%,特异性为84%,阳性预测值为87%,阴性预测值为94%。受试者工作特征曲线分析表明,该空腹G:I比值是检测胰岛素抵抗的最佳单一筛查指标。我们得出结论,空腹G:I比值可能作为肥胖非西班牙裔白人PCOS女性胰岛素抵抗的筛查试验。这可能是一个临床上有用的参数,用于选择最有可能对改善胰岛素敏感性的治疗干预有反应的PCOS女性。