Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevencion con Dieta Mediterranea (PREDIMED) trial
Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevencion con Dieta Mediterranea (PREDIMED) trial
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DOI：
10.1093/ajcn/nqy058
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发表时间：
2018-07-01
影响因子：
7.1
通讯作者：
Salas-Salvado, Jordi
中科院分区：
文献类型：
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作者：
Papandreou, Christopher;Bullo, Monica;Salas-Salvado, Jordi
背景资料：目前，人们对三甲基胺-N-氧化物（TMAO）在2型糖尿病（T2 D）中的作用有部分了解，但存在争议。目的：本研究的目的是探讨TMAO和相关代谢物与心血管疾病高风险受试者中T2 D风险的相关性。设计：这是一项病例队列设计研究，（PREDIMED）研究，251例T2 D事件和694例基线时无T2 D的受试者（641例非病例和53例重叠病例）的随机样本（中位随访时间：3.8年）。我们使用液相色谱-串联质谱法测量基线和1年后的血浆TMAO、l-肉毒碱、甜菜碱、溶血磷脂酰胆碱（LPC）和溶血磷脂酰乙醇胺（LPE）物质、磷酸胆碱、α-甘油磷酸胆碱和胆碱。我们使用加权的考克斯比例风险模型来检验相关性，考虑了Barlow方法的加权病例队列设计。结果：在调整公认的T2 D风险因素和多重检验后，基线TMAO和α-甘油磷酸胆碱最高四分位数的个体患T2 D的风险较低[HR（95%CI）：0.52（0.29，0.89）和0.46（0.24，0.89）]。比较甜菜碱的极端四分位数的HR（95%CI）为0.41（0.23，0.74）。对于C16：0 LPC、C18：1 LPC、C18：0 LPC、C20：4 LPC、C22：6 LPC、C18：1 LPC缩醛磷脂和C16：0 LPE，观察到相似的趋势。校正多重比较后，在最高的四分位数的油酸LPC血浆酶原浓度的1-y变化的参与者有一个较低的T2 D风险比参考quartile.Conclusion：血浆TMAO和某些代谢物浓度与T2 D风险之间的关联是否反映其病理生理或代表一种附带现象需要阐明。
Background: The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial.Objective: The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease.Design: This is a case-cohort design study within the Prevencion con Dieta Mediterranea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, a-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method.Results: After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and a-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16: 0 LPC, C18: 1 LPC, C18: 0 LPC, C20: 4 LPC, C22: 6 LPC, C18: 1 LPC plasmalogen, and C16: 0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile.Conclusion: Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated.