Department of Biochemistry, St. Petersburg State University, 199034 Saint Petersburg, Russia.
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, D-06120 Halle (Saale), Germany.
Int J Mol Sci. 2019 May 10;20(9):2329. doi: 10.3390/ijms20092329.
Type 2 diabetes mellitus (T2DM) is one of the most widely spread metabolic diseases. Because of its asymptomatic onset and slow development, early diagnosis and adequate glycaemic control are the prerequisites for successful T2DM therapy. In this context, individual amino acid residues might be sensitive indicators of alterations in blood glycation levels. Moreover, due to a large variation in the half-life times of plasma proteins, a generalized biomarker, based on multiple glycation sites, might provide comprehensive control of the glycemic status across any desired time span. Therefore, here, we address the patterns of glycation sites in highly-abundant blood plasma proteins of T2DM patients and corresponding age- and gender-matched controls by comprehensive liquid chromatography-mass spectrometry (LC-MS). The analysis revealed 42 lysyl residues, significantly upregulated under hyperglycemic conditions. Thereby, for 32 glycation sites, biomarker behavior was demonstrated here for the first time. The differentially glycated lysines represented nine plasma proteins with half-lives from 2 to 21 days, giving access to an integrated biomarker based on multiple protein-specific Amadori peptides. The validation of this biomarker relied on linear discriminant analysis (LDA) with random sub-sampling of the training set and leave-one-out cross-validation (LOOCV), which resulted in an accuracy, specificity, and sensitivity of 92%, 100%, and 85%, respectively.
2 型糖尿病（T2DM）是最广泛传播的代谢疾病之一。由于其无症状发作和缓慢发展，早期诊断和充分的血糖控制是成功治疗 T2DM 的前提。在这种情况下，个别氨基酸残基可能是血液糖化水平变化的敏感指标。此外，由于血浆蛋白的半衰期差异很大，基于多个糖化位点的通用生物标志物可能会在任何所需的时间段内全面控制血糖状态。因此，在这里，我们通过全面的液相色谱-质谱（LC-MS）研究了 T2DM 患者和相应年龄及性别匹配的对照者的高丰度血浆蛋白中的糖化位点模式。分析显示，在高血糖条件下，有 42 个赖氨酸残基显著上调。因此，这里首次证明了 32 个糖化位点的生物标志物行为。差异糖化的赖氨酸代表了半衰期为 2 至 21 天的 9 种血浆蛋白，从而可以基于多个蛋白特异性 Amadori 肽获得基于多个蛋白的综合生物标志物。该生物标志物的验证依赖于训练集的随机子采样和留一法交叉验证（LOOCV）的线性判别分析（LDA），其准确率、特异性和灵敏度分别为 92%、100%和 85%。
