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Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes

机译:循环代谢物的二十四小时节奏:体重和2型糖尿病的影响

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Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups—lean, overweight/obese (OW/OB), and OW/OB with T2DM—in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty-eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups—for example, phospholipids showed maximal difference at 5:00 AM (lean vs. OW/OB) and at 5:00 PM (OW/OB vs. T2DM). Metabolites that were identified with both robust 24-h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.—Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.
机译:用2型糖尿病(T2DM)的个体的代谢分析先前已被限于单时间点样品,忽略日期的变化。在这里,我们测试了我们的假设,即体重和T2DM在3岁匹配的男性群体,超重/肥胖(OW / OB)和OW / OB中,在24小时内,体重和T2DM影响每日节奏性和循环代谢物的循环代谢物的浓度。 T2DM-IN受控实验室条件,不会被大餐混淆。通过使用靶向液相色谱/质谱法代谢MOLICS,每2小时量化130个血浆代谢物,我们表明,通过增加的体重(130个)和T2DM(56×130个)显着改变平均代谢物浓度。 38%的代谢物在至少1个研究组中表现出每日节律,其中代谢物在> 1组中有节奏,其峰值时间可相当。评估日期的最佳时间以提供鉴别的生物标志物。这在代谢物类和研究组之间不同 - 例如,磷脂在5:00(瘦vs. ow / ob)和下午5:00(OW / OB与T2DM)上显示出最大差异。既有稳健的24-h节奏鉴定的代谢产物和研究组之间的显着浓度差异强调控制诊断和生物标志物发现的一天时间的重要性,提供了对当前单一抽样的重大改进。 - 伊瑟伍德,厘米,van der veen ,博士,约翰斯顿,JD,Skene,DJ二十四小时的循环代谢物的节奏性:体重和2型糖尿病的影响。

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