Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
Cardiovasc Ther. 2012 Feb;30(1):42-8. doi: 10.1111/j.1755-5922.2010.00177.x. Epub 2010 Jul 7.
Advanced glycation end products (AGEs) evoke oxidative stress generation and inflammatory reactions, thus being involved in vascular complications in diabetes. Since oxidative stress and inflammation impair insulin actions as well, it is conceivable that AGEs may play some role in insulin resistance. However, there is no clinical study to examine the relationship between serum levels of AGEs and insulin resistance. This study investigated whether serum AGE levels were independent correlates of insulin resistance in humans.
Three hundred twenty-two nondiabetic Japanese subjects (216 male and 106 female; mean age 61.5 ± 9.1 years) underwent a complete history and physical examination, determinations of blood chemistries, anthropometric and metabolic variables, including AGEs. Serum AGE levels were examined with an enzyme-linked immunosorbent assay.
Mean serum AGE levels were 8.96 ± 2.57 U/mL. In univariate analysis, waist circumference, diastolic blood pressure (BP), mean BP, AGEs, low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol (inversely), hemoglobin A1c (GHb), creatinine clearance, uric acid, and high sensitivity C-reactive protein were significantly associated with insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) index. After performing multiple regression analysis, waist circumference (P < 0.001), GHb (P < 0.001), triglycerides (P < 0.001), and AGEs (P < 0.01) still remained significant independently. When age-adjusted HOMA-IR levels stratified by AGE tertiles were compared using ANCOVA, a significant trend was demonstrated in both males and females.
The present study demonstrated for the first time that serum AGE levels were one of the independent correlates of HOMA-IR index, thus suggesting that AGEs may play some pathological role in insulin resistance in humans.
晚期糖基化终产物（AGEs）可引发氧化应激和炎症反应，从而导致糖尿病的血管并发症。由于氧化应激和炎症也会损害胰岛素的作用，因此可以想象 AGEs 可能在胰岛素抵抗中发挥一定作用。然而，目前尚无临床研究来检测血清 AGE 水平与胰岛素抵抗之间的关系。本研究旨在探讨血清 AGE 水平是否与人类胰岛素抵抗有关。
322 名非糖尿病的日本受试者（216 名男性和 106 名女性；平均年龄 61.5 ± 9.1 岁）接受了全面的病史和体格检查，进行了血液化学、人体测量和代谢变量的测定，包括 AGEs。采用酶联免疫吸附试验检测血清 AGE 水平。
平均血清 AGE 水平为 8.96 ± 2.57 U/mL。在单变量分析中，腰围、舒张压（BP）、平均 BP、AGEs、低密度脂蛋白（LDL）胆固醇、甘油三酯、高密度脂蛋白（HDL）胆固醇（呈负相关）、糖化血红蛋白（GHb）、肌酐清除率、尿酸和高敏 C 反应蛋白与稳态模型评估的胰岛素抵抗指数（HOMA-IR）显著相关。进行多元回归分析后，腰围（P < 0.001）、GHb（P < 0.001）、甘油三酯（P < 0.001）和 AGEs（P < 0.01）仍然独立显著。使用 ANCOVA 比较按 AGE 三分位数分层的年龄校正后 HOMA-IR 水平时，在男性和女性中均显示出显著的趋势。
本研究首次表明，血清 AGE 水平是 HOMA-IR 指数的独立相关因素之一，提示 AGEs 可能在人类胰岛素抵抗中发挥一定的病理作用。
