PDF(Pubmed)
Abstract：
Metformin is the most widely used drug in type 2 diabetes. Regular metformin use has been associated with changes in concentrations of amino acids. In the present study, we used valid stable-isotope labeled GC-MS methods to measure amino acids and metabolites, including creatinine as well as malondialdehyde (MDA), as an oxidative stress biomarker in plasma, urine, and dialysate samples in a patient at admission to the intensive care unit and during renal replacement treatment because of metformin-associated lactic acidosis (MALA, 21 mM lactate, 175 µM metformin). GC-MS revealed lower concentrations of amino acids in plasma, normal concentrations of the nitric oxide (NO) metabolites nitrite and nitrate, and normal concentrations of MDA. Renal tubular reabsorption rates were altered on admission. The patient received renal replacement therapy over 50 to 70 h of normalized plasma amino acid concentrations and their tubular reabsorption, as well as the tubular reabsorption of nitrite and nitrate. This study indicates that GC-MS is a versatile analytical tool to measure different classes of physiological inorganic and organic substances in complex biological samples in clinical settings such as MALA.
摘要：
二甲双胍是2型糖尿病中应用最广泛的药物。常规使用二甲双胍与氨基酸浓度的变化有关。在本研究中,我们使用有效的稳定同位素标记的GC-MS方法来测量氨基酸和代谢物，包括肌酐和丙二醛（MDA），作为血浆中的氧化应激生物标志物，尿液,以及因二甲双胍相关乳酸性酸中毒而入院至重症监护病房和肾脏替代治疗期间患者的透析液样本（MALA，21mM乳酸，175µM二甲双胍)。GC-MS显示血浆中氨基酸浓度较低，正常浓度的一氧化氮（NO）代谢物亚硝酸盐和硝酸盐，和正常浓度的MDA。入院时肾小管重吸收率改变。患者接受肾脏替代治疗超过50至70小时的标准化血浆氨基酸浓度及其肾小管重吸收，以及亚硝酸盐和硝酸盐的管状重吸收。这项研究表明，GC-MS是一种通用的分析工具，可在临床环境（如MALA）中测量复杂生物样品中不同类别的生理无机和有机物质。
