Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
Department of Physics and Kitasato University School of Science, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan.
Sci Rep. 2020 Jan 14;10(1):268. doi: 10.1038/s41598-019-57095-2.
Oxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity. We used liquid chromatography-high resolution mass spectrometry (LC-MS) to show that oxidised and non-oxidised Met residues at position 147 of human serum albumin (Met) can be accurately and reproducibly quantified with stable isotope-labelled peptides. Met oxidation was significantly higher in patients with diabetes than in controls. Least square multivariate analysis revealed that glycated haemoglobin (HbA) and glycated albumin (GA) did not significantly influence Met oxidation, but the GA/HbA ratio, which reflects glycaemic excursions, independently affected Met oxidation status. Continuous glucose monitoring revealed that Met oxidation strongly correlates with the standard deviation of sensor glucose concentrations and the time spent with hypoglycaemia or hyperglycaemia each day. Thus, glycaemic variability and hypoglycaemia in diabetes may be associated with greater oxidation of Met. Renal function, high-density lipoprotein-cholesterol and serum bilirubin were also associated with the oxidation status of Met. In conclusion, the quantification of oxidised and non-oxidised Met in serum albumin using our LC-MS methodology could be used to assess the degree of intravascular oxidative stress induced by hypoglycaemia and glycaemic fluctuations in diabetes.
氧化应激与许多慢性疾病有关，这引起了人们对鉴定能够准确评估其严重程度的临床生物标志物的兴趣。我们使用液相色谱-高分辨率质谱（LC-MS）表明，可以使用稳定同位素标记肽准确且可重复地定量人血清白蛋白（Met）位置 147 处的氧化和非氧化 Met 残基。糖尿病患者的 Met 氧化明显高于对照组。最小二乘多元分析表明，糖化血红蛋白（HbA）和糖化白蛋白（GA）对 Met 氧化没有显著影响，但反映血糖波动的 GA/HbA 比值独立影响 Met 氧化状态。连续血糖监测显示，Met 氧化与传感器葡萄糖浓度的标准差以及每天低血糖或高血糖的时间强烈相关。因此，糖尿病患者的血糖变异性和低血糖可能与 Met 的氧化程度增加有关。肾功能、高密度脂蛋白胆固醇和血清胆红素也与 Met 的氧化状态有关。总之，使用我们的 LC-MS 方法定量血清白蛋白中的氧化和非氧化 Met 可用于评估糖尿病患者低血糖和血糖波动引起的血管内氧化应激程度。
