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首页> 外文期刊>Diabetic medicine: A journal of the British Diabetic Association >Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy ( CIMT CIMT ) trial
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Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy ( CIMT CIMT ) trial

机译：二甲双胍对蛋白胰岛素和二甲双胍治疗（CIMT CIMT）试验中血浆代谢物谱的影响

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Abstract Aim Metformin is the first‐line treatment for Type 2 diabetes. However, not all people benefit from this drug. Our aim was to investigate the effects of metformin on the plasma metabolome and whether the pretreatment metabolite profile can predict HbA 1c outcome. Methods Post hoc analysis of the Copenhagen Insulin and Metformin Therapy ( CIMT ) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non‐target method to analyse 87 plasma metabolites in participants with Type 2 diabetes ( n = 370) who were randomized in a 1?:?1 ratio to 18?months of metformin or placebo treatment. Metabolites were measured by liquid chromatography–mass spectrometry at baseline and at 18‐month follow‐up and the data were analysed using a linear mixed‐effect model. Results At baseline, participants who were on metformin before the trial ( n = 312) had higher levels of leucine/isoleucine and five lysophosphatidylethanolamines ( LPE s), and lower levels of carnitine and valine compared with metformin‐na?ve participants ( n = 58). At follow‐up, participants randomized to metformin ( n = 188) had elevated levels of leucine/isoleucine and reduced carnitine, tyrosine and valine compared with placebo ( n = 182). At baseline, participants on metformin treatment with the highest levels of carnitine C10:1 and leucine/isoleucine had the lowest HbA 1c ( P ‐interaction = 0.02 and 0.03, respectively). This association was not significant with HbA 1c at follow‐up. Conclusions Metformin treatment is associated with decreased levels of valine, tyrosine and carnitine, and increased levels of leucine/isoleucine. None of the identified metabolites can predict the HbA 1c ‐lowering effect of metformin. Further studies of the association between metformin, carnitine and leucine/isoleucine are warranted.
机译：摘要AIM二甲双胍是2型糖尿病的一线治疗。然而，并非所有人都受益于这种药物。我们的目的是探讨二甲双胍对血浆代谢物的影响以及预处理代谢物型是否可以预测HBA 1C结果。方法对哥本哈根胰岛素和二甲双胍治疗（CIMT）审判的后HOC分析，2008年5月至2012年12月的多期式研究。我们使用非目标方法来分析与2型糖尿病（N = 370）的参与者中的87种血浆代谢物（n = 370），他在1中随机化？：1比与18个月的二甲双胍或安慰剂治疗。在基线下通过液相色谱 - 质谱测量代谢物，并且在18个月的随访中，使用线性混合效应模型分析数据。结果在基线上，在试验前（n = 312）在二甲双胍上的参与者具有较高水平的亮氨酸/异亮氨酸和五种溶血磷酸氨氨酸乙醇胺（LPE S），以及与二甲双胍-NA'VE参与者相比的肉碱和缬氨酸含量降低（n = 58）。在随访中，与二甲双胍（n = 188）随机化的参与者含量升高，与安慰剂（n = 182）相比亮氨酸/异亮氨酸和降低的肉碱，酪氨酸和缬氨酸（n = 182）。在基线时，具有最高水平肉碱C10：1和亮氨酸/异亮氨酸的二甲双胍治疗的参与者具有最低的HBA 1C（P-Interaction = 0.02和0.03）。这种关联在随访时与HBA 1C不显着。结论二甲双胍治疗与缬氨酸，酪氨酸和肉碱水平降低有关，亮氨酸/异亮氨酸水平增加。没有鉴定的代谢物可以预测二甲双胍的HBA 1C -Lowering效应。有必要进一步研究二甲双胍，肉碱和亮氨酸/异亮氨酸之间的关联。

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