Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria.
Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria.
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DOI：
10.1371/journal.pone.0244402
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Rossing P
中科院分区：
文献类型：
--
作者：
Winther SA;Øllgaard JC;Hansen TW;von Scholten BJ;Reinhard H;Ahluwalia TS;Wang Z;Gæde P;Parving HH;Hazen S;Pedersen O;Rossing P
三甲胺-N-氧化物（TMAO）途径与肠道微生物群有关，并与心血管疾病（CVD）风险相关。我们研究了TMAO途径中的四种血浆代谢物与2型糖尿病（T2D）合并白蛋白尿患者的全因死亡率、心血管疾病风险以及肾功能恶化之间的关联。
采用液相色谱 - 串联质谱法在基线时对311名T2D合并白蛋白尿患者的血浆TMAO、胆碱、肉碱和甜菜碱浓度进行了测量。随访期间的全因死亡率以及致命/非致命心血管疾病信息从相关登记处获取。对每种代谢物以及四种代谢物的加权总分与各项终点指标之间的关联进行了检测。在随访就诊时测量血清肌酐，将肾功能终点定义为估算肾小球滤过率（eGFR）下降≥30%。使用针对传统风险因素进行调整的比例风险模型对关联进行分析。
基线平均（标准差）年龄为57.2（8.2）岁，75%为男性。随访时间最长达21.9年（死亡率的中位随访时间（四分位间距）为6.8（6.1 - 15.5）年，心血管疾病事件的中位随访时间为6.5（5.5 - 8.1）年）。单个代谢物以及加权总分与全因死亡率（n = 106）或心血管疾病（n = 116）无关（校正后p≥0.09）。较高的胆碱、肉碱以及四种代谢物的加权总分与eGFR下降风险较高相关（n = 106）（校正后p = 0.001、p = 0.03和p<0.001）。
在T2D合并白蛋白尿患者中，较高的胆碱、肉碱以及TMAO途径中四种代谢物的加权总和是长期随访期间肾功能恶化的风险标志物。TMAO途径的代谢物与全因死亡率或心血管疾病风险并无独立关联。
The trimethylamine N-oxide (TMAO) pathway is related to intestinal microbiota and has been associated to risk of cardiovascular disease (CVD). We investigated associations between four plasma metabolites in the TMAO pathway and risk of all-cause mortality, CVD and deterioration in renal function in individuals with type 2-diabetes (T2D) and albuminuria. Plasma concentrations of TMAO, choline, carnitine, and betaine were measured by liquid chromatography-tandem mass spectrometry at baseline in 311 individuals with T2D and albuminuria. Information on all-cause mortality and fatal/non-fatal CVD during follow-up was obtained from registries. The association of each metabolite, and a weighted sum score of all four metabolites, with the endpoints were examined. Serum creatinine was measured at follow-up visits and the renal endpoint was defined as eGFR-decline of ≥30%. Associations were analysed using proportional hazards models adjusted for traditional risk factors. Baseline mean(SD) age was 57.2(8.2) years and 75% were males. Follow-up was up to 21.9 years (median (IQR) follow-up 6.8 (6.1–15.5) years for mortality and 6.5 (5.5–8.1) years for CVD events). The individual metabolites and the weighted sum score were not associated with all-cause mortality (n = 106) or CVD (n = 116) (adjusted p≥0.09). Higher choline, carnitine and the weighted sum score of the four metabolites were associated with higher risk of decline in eGFR (n = 106) (adjusted p = 0.001, p = 0.03 and p<0.001, respectively). In individuals with T2D and albuminuria, higher choline, carnitine and a weighted sum of four metabolites from the TMAO pathway were risk markers for deterioration in renal function during long-term follow-up. Metabolites from the TMAO pathway were not independently related to risk of all-cause mortality or CVD.
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影响因子：
3.7
作者：
Lever M;George PM;Slow S;Bellamy D;Young JM;Ho M;McEntyre CJ;Elmslie JL;Atkinson W;Molyneux SL;Troughton RW;Frampton CM;Richards AM;Chambers ST
通讯作者：
Chambers ST
影响因子：
--
作者：
Dong Z;Liang Z;Guo M;Hu S;Shen Z;Hai X
通讯作者：
Hai X
影响因子：
5.4
作者：
Heianza Y;Ma W;Manson JE;Rexrode KM;Qi L
通讯作者：
Qi L
影响因子：
5.3
作者：
Mueller, Daniel M.;Allenspach, Martina;von Eckardstein, Arnold
通讯作者：
von Eckardstein, Arnold
影响因子：
168.9
作者：
Gæde, P;Vedel, P;Pedersen, O
通讯作者：
Pedersen, O