Spiller Sandro, Li Yichao, Blüher Matthias, Welch Lonnie, Hoffmann Ralf
Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig, Germany.
Center for Biotechnology and Biomedicine (BBZ), Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany.
Clin Proteomics. 2017 Mar 28;14:10. doi: 10.1186/s12014-017-9145-1. eCollection 2017.
Recent epidemiological studies indicate that only 30-50% of undiagnosed type 2 diabetes mellitus (T2DM) patients are identified using glycated hemoglobin (HbA) and elevated fasting plasma glucose (FPG) levels. Thus, novel biomarkers for early diagnosis and prognosis are urgently needed for providing early and personalized treatment.
Here, we studied the glycation degrees of 27 glycation sites representing nine plasma proteins in 48 newly diagnosed male T2DM patients and 48 non-diabetic men matched for age (range 35-65 years). Samples were digested with trypsin and enriched for glycated peptides using boronic acid affinity chromatography. Quantification relied on mass spectrometry (multiple reaction monitoring) using isotope-labelled peptides as internal standard.
The combination of glycated lysine-141 of haptoglobin (HP K141) and HbA provided a sensitivity of 94%, a specificity of 98%, and an accuracy of 96% to identify T2DM. A set of 15 features considering three glycation sites in human serum albumin, HP K141, and 11 routine laboratory measures of T2DM, metabolic syndrome, obesity, inflammation, and insulin resistance provided a sensitivity of 98%, a specificity of 100%, and an accuracy of 99% for newly diagnosed T2DM patients.
Our studies demonstrated the great potential of glycation sites in plasma proteins providing an additional diagnostic tool for T2DM and elucidating that the combination of these sites with HbA and FPG could improve the diagnosis of T2DM.
近期流行病学研究表明，仅通过糖化血红蛋白（HbA）和空腹血糖（FPG）水平升高来识别未诊断的2型糖尿病（T2DM）患者，仅有30%-50%能被确诊。因此，迫切需要新的生物标志物用于早期诊断和预后评估，以提供早期个性化治疗。
在此，我们研究了48例新诊断的男性T2DM患者和48例年龄匹配（35-65岁）的非糖尿病男性中，代表9种血浆蛋白的27个糖基化位点的糖基化程度。样本用胰蛋白酶消化，并用硼酸亲和色谱法富集糖基化肽段。定量依赖于使用同位素标记肽作为内标的质谱法（多反应监测）。
结合触珠蛋白的糖化赖氨酸-141（HP K141）和HbA，识别T2DM的灵敏度为94%，特异性为98%，准确性为96%。考虑人血清白蛋白中的3个糖基化位点、HP K141以及11项T2DM、代谢综合征、肥胖、炎症和胰岛素抵抗的常规实验室指标组成的15个特征集，对新诊断的T2DM患者的灵敏度为98%，特异性为100%，准确性为99%。
我们的研究证明了血浆蛋白糖基化位点具有巨大潜力，可为T2DM提供额外的诊断工具，并阐明这些位点与HbA和FPG的组合可改善T2DM的诊断。
