School of Pharmacy, East China University of Science & Technology, Shanghai, 200237, China.
Talanta. 2011 Sep 30;85(4):1711-20. doi: 10.1016/j.talanta.2011.05.036. Epub 2011 Jun 15.
Type 2 diabetes mellitus (T2DM) and its attendant complications, such as diabetic nephropathy (DN), impose a significant societal and economic burden. The investigation of discovering potential biomarkers for T2DM and DN will facilitate the prediction and prevention of diabetes. Phospholipids (PLs) and their metabolisms are closely allied to nosogenesis and aggravation of T2DM and DN. The aim of this study is to characterize the human plasma phospholipids in T2DM and DN to identify potential biomarkers of T2DM and DN. Normal phase liquid chromatography coupled with time of flight mass spectrometry (NPLC-TOF/MS) was applied to the plasma phospholipids metabolic profiling of T2DM and DN. The plasma samples from control (n=30), T2DM subjects (n=30), and DN subjects (n=52) were collected and analyzed. The significant difference in metabolic profiling was observed between healthy control group and DM group as well as between control group and DN group by the help of partial least squares discriminant analysis (PLS-DA). PLS-DA and one-way analysis of variance (ANOVA) were successfully used to screen out potential biomarkers from complex mass spectrometry data. The identification of molecular components of potential biomarkers was performed on Ion trap-MS/MS. An external standard method was applied to quantitative analysis of potential biomarkers. As a result, 18 compounds in 7 PL classes with significant regulation in patients compared with healthy controls were regarded as potential biomarkers for T2DM or DN. Among them, 3 DM-specific biomarkers, 8 DN-specific biomarkers and 7 common biomarkers to DM and DN were identified. Ultimately, 2 novel biomarkers, i.e., PI C18:0/22:6 and SM dC18:0/20:2, can be used to discriminate healthy individuals, T2DM cases and DN cases from each other group.
2 型糖尿病（T2DM）及其并发症，如糖尿病肾病（DN），给社会和经济带来了巨大负担。寻找 T2DM 和 DN 的潜在生物标志物的研究将有助于预测和预防糖尿病。磷脂（PLs）及其代谢与 T2DM 和 DN 的发病和加重密切相关。本研究旨在对 T2DM 和 DN 患者的人血浆磷脂进行特征分析，以鉴定 T2DM 和 DN 的潜在生物标志物。采用正相液相色谱-飞行时间质谱（NPLC-TOF/MS）对 T2DM 和 DN 的血浆磷脂代谢谱进行分析。收集并分析了来自对照组（n=30）、T2DM 组（n=30）和 DN 组（n=52）的血浆样本。通过偏最小二乘判别分析（PLS-DA）发现，健康对照组与 DM 组以及对照组与 DN 组之间的代谢谱存在显著差异。PLS-DA 和单因素方差分析（ANOVA）成功地从复杂的质谱数据中筛选出潜在的生物标志物。通过离子阱-MS/MS 对潜在生物标志物的分子成分进行鉴定。采用外标法对潜在生物标志物进行定量分析。结果显示，与健康对照组相比，7 类 PL 中有 18 种化合物在患者中存在显著调节，被认为是 T2DM 或 DN 的潜在生物标志物。其中，鉴定出 3 种 DM 特异性生物标志物、8 种 DN 特异性生物标志物和 7 种 DM 和 DN 共同的生物标志物。最终，2 种新型生物标志物，即 PI C18:0/22:6 和 SM dC18:0/20:2，可用于区分健康个体、T2DM 患者和 DN 患者。
