Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome
Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome
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DOI：
10.1111/j.1365-2265.2004.02170.x
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Creatsas, G
中科院分区：
文献类型：
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作者：
Diamanti-Kandarakis, E;Piperi, C;Creatsas, G
目的多囊卵巢综合征（PCOS）女性携带多种心血管危险因素，被认为是动脉粥样硬化的高危人群。晚期糖基化终产物（AGE）通过与特异性受体（RAGE）的相互作用发挥作用，其浓度升高与动脉粥样硬化过程中的细胞和组织损伤有关。我们研究了29名年轻PCOS女性的血清AGE水平及其循环单核细胞中受体RAGE的表达，并将其与22名健康对照女性的水平进行了比较。测量/结果PCOS女性血清AGE蛋白水平高于健康个体（9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001）， PCOS女性单核细胞RAGE表达高于对照组（30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02）。AGE蛋白与睾酮水平呈正相关（r = 0.73, P < 0.0001）。在口服葡萄糖耐量试验（OGTT）中控制体重指数（BMI）、胰岛素水平和葡萄糖曲线下面积（AUCGLU）后，AGE蛋白与T水平的相关性仍然很高（偏相关系数= 0.61,P = 0.0001）。AGE蛋白与游离雄激素指数（FAI） （r = 0.58, P < 0.0001）、腰臀比（WHR） （r = 0.31, P < 0.02）、胰岛素（r = 0.46, P < 0.001）、稳态模型评估（HOMA） （r = 0.47, P < 0.0001）、AUCGLU （r = 0.52, P < 0.002）、RAGE （r = 0.59, P < 0.01）呈正相关。AGE蛋白与葡萄糖/胰岛素比值（GLU/INS） （r = -0.35, P < 0.01）、胰岛素敏感性定量检查指数（QUICKI） （r =-0.50, P < 0.01）呈负相关。在多元回归分析中，T是BMI、胰岛素、SHBG和AUCGLU之间AGE水平的唯一独立预测因子（P < 0.0001, b = 0.044）（校正R-2 = 0.59, F = 44.41, P < 0.0001）。这些数据首次清楚地表明，与对照组相比，无明显高血糖的PCOS女性AGE水平升高，RAGE表达升高。
Objective Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end-products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes.Design/patients We investigated serum AGE levels in 29 young women with PCOS as well as the expression of their receptor, RAGE, in circulating monocytes and compared them levels with 22 healthy control women.Measurements/results Women with PCOS had higher levels of serum AGE proteins compared to healthy individuals (9.81 +/- 0.16 vs. 5.11 +/- 0.16, P < 0.0001), and increased RAGE expression was observed in monocytes of PCOS women compared to controls (30.91 +/- 10.11 vs. 7.97 +/- 2.61, P < 0.02). A positive correlation was observed between AGE proteins and testosterone (T) levels (r = 0.73, P < 0.0001). The correlation between AGE proteins and T levels remained high (partial correlation coefficient = 0.61, P = 0.0001) after controlling for body mass index (BMI), insulin levels and the area under the curve for glucose (AUCGLU) during an oral glucose tolerance test (OGTT). A positive correlation was also observed between AGE proteins and the free androgen index (FAI) (r = 0.58, P < 0.0001), waist-to-hip ratio (WHR) (r = 0.31, P < 0.02), insulin (r = 0.46, P < 0.001), homeostasis model assessment (HOMA) (r = 0.47, P < 0.0001), AUCGLU (r = 0.52, P < 0.002) and RAGE (r = 0.59, P < 0.01). A negative correlation was observed between AGE proteins and glucose/insulin ratio (GLU/INS) (r = -0.35, P < 0.01), and the quantitative insulin sensitivity check index (QUICKI) (r =-0.50, P < 0.01). In multiple regression analysis T was the only independent predictor of AGE levels (P < 0.0001, b = 0.044) between BMI, insulin, SHBG and AUCGLU (adjusted R-2 = 0.59, F = 44.41, P < 0.0001).Conclusion These data clearly demonstrate, for the first time, that PCOS women without overt hyperglycaemia have increased AGE levels and elevated RAGE expression when compared with controls.