Development of a new assay method for oxidative DNA damages in diabetes

有几条证据表明氧化DNA损伤和糖尿病并发症之间可能存在联系。在正常人和2型糖尿病患者中，我们发现尿液和/或白细胞8-oxodG与胰岛素敏感性有显著关系。在一项横断面研究中，我们还证明了尿液和/或白细胞8-oxodG与糖尿病肾病和视网膜病变的严重程度之间的显著关系。在一项前瞻性研究中，我们证明了尿8-oxodG水平与肾病的发生之间存在显著的相关性。这项前瞻性研究还表明，白细胞8-oxodG水平与视网膜病变的发生密切相关。因此，本研究提供了氧化应激增强在糖尿病肾病和视网膜病变的发病机制中起主要作用的证据。我们还开发了新的检测系统，使用气相色谱/质谱仪(GC/MS)来检测嘧啶氧化产物、嘌呤氧化产物、碱基脱氨产物、碱氯化产物。利用该检测系统，我们已经对糖尿病的DNA氧化损伤和糖尿病并发症的发病机制进行了精确的表征。

There were several line of evidence to demonstrate a possible relationship oxidative DNA damages and diabetic complications. We demonstrated a significant relationship between the urinary and/or leukocyte 8-oxodG and insulin sensitivity in normal subjects and type 2 diabetic patients. We also demonstrated significant relationship between the urinary and/or leukocyte 8-oxodG and the severity of diabetic nephropathy and retinopathy in a cross-sectional study. We demonstrates a significant association between the urinary 8-oxodG levels and the development of nephropathy in a prospective study. This prospective study also demonstrates a significant association between the leukocyte 8-oxodG levels and the development of retinopathy. Thus, the study provides evidence that augmented oxidative stress has a primary role in the pathogenesis of diabetic nephropathy and retinopathy.We also developed the new assay system using gas-chromatography/mass spectrometry (GC/MS) to measure pyrimidine oxidation products, purine oxidation products, base deamination products, base chlorination products. Using this assay system, we have performed the precise characterization of oxidative DNA damages in diabetes mellitus and pathogenesis of diabetic complications.