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首页> 外文期刊>Analytical chemistry >Application of a Pseudotargeted MS Method for the Quantification of Glycated Hemoglobin for the Improved Diagnosis of Diabetes Mellitus
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Application of a Pseudotargeted MS Method for the Quantification of Glycated Hemoglobin for the Improved Diagnosis of Diabetes Mellitus

机译：假靶法MS法在糖尿病诊断改善糖尿病诊断中的应用

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摘要

Proteins in a human body continuously undergo glycation reactions with reducing sugars, forming early as well as advanced glycation end-products (AGEs) which are highly disease-relevant. Specifically, N-1-(deoxyfructosyl) valine of beta-hemoglobin (HbA1c) has been considered as a marker of diabetes, but the exact map of glycated Hb peptides corelated with diabetes in different stages is poorly studied. Here, the pseudotargeted parallel reaction monitoring (PRM) method combined with relative retention time (iRT) endogenous peptides was proposed for exploring the roles of deoxyfructosyl (DF-), carboxymethyl (CM-), and carboxyethyl (CE-) based Hb modifications in clinical prognosis and diagnosis of type 2 diabetes mellitus (T2DM) and its complication. For building the pseudotargeted list, data-dependent acquisition (DDA) combined with multiple enzyme digestion was employed for the comprehensive identification of the three types of modification in vitro Hb and in vivo Hb. The introduction of the endogenous iRT peptides during PRM analysis facilitates being able to obtain accurate quantitative results. When applying this new strategy to quantify the three kinds of glycated Hb peptides in clinical samples, patients with T2DM in different pathophysiological conditions were fully distinguished from the controls, indicating the necessity of adopting multiple glycation types for the improved diagnosis of T2DM. Taken together, the newly developed pseudotargeted PRM method not only expands the horizons of glycated Hb by reliably assessing the actual status of T2DM but also reveals that endogenous iRT might be a viable option for label-free quantitative analysis.
机译：人体中的蛋白质连续地与还原糖进行糖化反应，早期形成，以及高度疾病相关的先进糖糖末端产物（年龄）。具体地，β-血红蛋白（HBA1c）的N-1-（脱氧糖基）缬氨酸被认为是糖尿病的标志物，但研究了不同阶段的糖尿病患者的糖化Hb肽的确切图谱。这里，提出了与相对保留时间（IRT）内源肽组合的假靶向并联反应监测（PRM）方法用于探索脱氧糖基（DF-），羧甲基（CM-）和基于羧乙基（CE-）的HB改性的作用2型糖尿病（T2DM）及其复杂性的临床预后及诊断。对于构建假靶案，采用数据依赖性采集（DDA）与多种酶消化相结合，用于综合体外Hb和体内Hb中的三种改性类型的综合鉴定。在PRM分析期间引入内源性IRT肽有助于能够获得准确的定量结果。当应用这种新策略来量化临床样本中的三种糖化HB肽时，不同病理生理病症中T2DM的患者完全与对照区分开，表明需要采用多种糖化类型进行改善的T2DM诊断。结合在一起，新开发的假冒PRM方法不仅通过可靠地评估T2DM的实际状态而扩大糖化Hb的视野，还揭示了内源性IRT可能是无标签定量分析的可行选择。

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  • 来源
    《Analytical chemistry》 |2020年第4期|共9页
  • 作者

    Li Weifeng; Lin Lin; Yan Dewen; Jin Yu; Xu Yun; Li Yinghong; Ma Min; Wu Zhengzhi;

  • 作者单位

    Jinan Univ Integrated Chinese &

    Western Med Postdoctoral Res Guangzhou 510632 Peoples R China;

    Southern Univ Sci &

    Technol Sustech Core Res Facil Shenzhen 518055 Peoples R China;

    Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518020 Peoples R China;

    Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518020 Peoples R China;

    Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518020 Peoples R China;

    Shenzhen Univ Affiliated Hosp 1 Shenzhen Peoples Hosp 2 Shenzhen 518020 Peoples R China;

    Jinan Univ Integrated Chinese &

    Western Med Postdoctoral Res Guangzhou 510632 Peoples R China;

    Jinan Univ Integrated Chinese &

    Western Med Postdoctoral Res Guangzhou 510632 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分析化学;
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