孕妇妊娠早期的氧化三甲胺及其代谢产物与超重的关联

曹舒; 冷俊宏; 李卫芹; 房中则; 杨西林; 霍晓旭

doi:10.16462/j.cnki.zhjbkz.2021.02.010

孕妇妊娠早期的氧化三甲胺及其代谢产物与超重的关联

doi: 10.16462/j.cnki.zhjbkz.2021.02.010

1.
300070 天津，天津医科大学公共卫生学院流行病与卫生统计学系
2.
300070 天津，天津市妇女儿童保健中心项目办公室

基金项目:

国家自然科学基金青年科学基金 81900724

国家自然科学基金 81870549

详细信息

通讯作者:
霍晓旭，E-mail: huoxiaoxu@tmu.edu.cn

中图分类号: R714.256
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出版历程
- 收稿日期: 2020-07-15
- 修回日期: 2020-11-08
- 刊出日期: 2021-02-10

Correlation analysis on trimethylamine N-oxide and its metabolites in early pregnancy with overweight

1.
School of Public Health, Tianjin Medical University, Tianjin 300070, China
2.
Tianjin Women and Children Health Center, Tianjin 300070, China

Funds:

Project of Youth Science Foundation of National Natural Science Foundation of China 81900724

National Natural Science Foundation of China 81870549

More Information

Corresponding author: HUO Xiao-xu, E-mail: huoxiaoxu@tmu.edu.cn

摘要

摘要: 目的探讨妊娠早期在不同的体重状态下，孕妇氧化三甲胺(trimethylamine N-oxide, TMAO)及其代谢产物的分布差异，并分析TMAO及其代谢产物与超重之间的关联。方法天津市妇女儿童保健中心于2010年10月1日-2012年8月31日在天津市建立了一个由22 302名孕妇组成的妊娠队列，随后建立了以妊娠糖尿病(gestational diabetes mellitus, GDM)作为目标疾病的巢式病例对照研究，包括243名在怀孕24~28周发展为GDM的孕妇，同时根据(年龄±1)岁进行1:1匹配，最终纳入分析的研究对象为486名。采用液相色谱-串联质谱分析对血清TMAO及其代谢产物进行测定。将研究对象按照BMI≥24.0 kg/m²及BMI < 24.0 kg/m²分为超重组和非超重组，通过百分位数法将TMAO及其代谢产物分为高、低水平组，采用二元Logistic回归分析模型进行分析。结果超重组的三甲胺(trimethylamine, TMA)水平高于非超重组，差异具有统计学意义(Z=-2.747, P=0.006)。Logistic回归分析模型分析显示，未调整混杂因素时，与TMA低水平的孕妇相比，TMA≥264.5 nmol/ml时超重的OR值是1.771(95% CI: 1.193~2.629, P=0.005)；调整混杂因素后，TMA≥264.5 nmol/ml时超重的OR值是1.734(95% CI: 1.063~2.827, P=0.027)。结论妊娠早期的TMA水平与孕妇超重具有相关性，通过调节TMAO及其代谢物的水平可能为肥胖症、糖尿病等代谢综合征的控制、治疗提供新思路。
- 妊娠早期 /
- 氧化三甲胺 /
- 超重
Abstract: Objective To explore the differences in the distribution of trimethylamine N-oxide (TMAO) and its metabolites in pregnant women under different weight status in early pregnancy, and analyze the relationship between TMAO and its metabolites and overweight. Methods A pregnancy cohort of 22 302 pregnant women was established in Tianjin from October 1 2010 to August 31 2012, and then gestational diabetes mellitus (GDM) was selected as the target disease. The nested case-control study included 243 pregnant women who developed GDM between 24 and 28 weeks of pregnancy. At the same time, a 1:1 match was made according to (age ±1) year. The final analysis included 486 subjects. The serum TMAO and its metabolites were determined by liquid chromatography-tandem mass spectrometry. Subjects were divided into overweight group and non-overweight group according to BMI≥24.0 kg/m² and BMI < 24.0 kg/m², TMAO and its metabolites were divided into high and low levels by percentile method, and binary logistic regression analysis was performed. Results The level of overweight group trimethylamine (TMA) was significantly higher than that of non-overweight group, the difference was statistically significant (Z=-2.747, P=0.006). Logistic regression analysis showed that when the confounding factors were not adjusted, compared with pregnant women with low TMA, the OR value of overweight at TMA≥264.5 nmol/mL was 1.771 (95% CI: 1.193-2.629, P=0.005); After adjusting for confounding factors, the OR value of overweight at TMA≥264.5 nmol/mL was 1.734 (95% CI: 1.063-2.827, P=0.027). Conclusions The level of TMA in early pregnancy is significantly related to the overweight of pregnant women. By adjusting the level of TMAO and its metabolites, it may provide new ideas for the control and treatment of metabolic syndromes such as obesity and diabetes.
- Early pregnancy /
- Trimethylamine oxide /
- Overweight

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表 1 不同BMI孕妇的临床特点比较[n(%)]

Table 1. Clinical characteristics of pregnant women with different BMI [n(%)]

变量	BMI < 24.0 kg/m²(n=320)	BMI≥24.0 kg/m²(n=166)	t/χ²/z值	P值
年龄(x±s, 岁)	29.0±2.9	29.6±3.2	-1.911	0.057^a
身高(x±s, cm)	163.2±4.8	163.0±4.7	0.496	0.620^a
体重(x±s, kg)	55.4±6.4	71.6±8.3	-23.797	< 0.001^a
BMI(x±s, kg/m²)	20.8±2.0	26.9±2.6	-29.073	< 0.001^a
孕周(x±s, 周)	10.1±2.0	10.2±2.2	-1.017	0.310^a
DBP(x±s, mmHg)	103.8±9.5	110.6±11.4	-6.999	< 0.001^a
SBP(x±s, mmHg)	67.8±7.2	72.0±8.6	-5.669	< 0.001^a
民族
汉族	310(96.9)	162(97.6)	0.026	0.872^b
其他民族	10(3.1)	4(2.4)
教育经历
受教育>12年	274(85.6)	125(75.3)	7.926	0.005^b
受教育≤12年	46(14.4)	41(24.7)
一级亲属糖尿病家族史
有	22(6.9)	22(13.3)	5.400	0.02^b
无	298(93.1)	144(86.7)
产次
＜1	303(94.7)	157(94.6)	0.003	0.960^b
≥1	17(5.3)	9(5.4)
既往吸烟
是	17(5.3)	11(6.6)	0.348	0.555^b
否	303(94.7)	155(93.4)
既往饮酒
是	87(27.2)	42(25.3)	0.199	0.655^b
否	233(72.8)	124(74.7)
孕早期FPG[M(P₂₅, P₇₅), mmol/L]	4.6(4.2, 5.0)	4.8(4.4, 5.2)	7.908	0.007^c
ALT [M(P₂₅, P₇₅), U/L]	16.0(11.0, 21.9)	19.0(13.0, 29.8)	-3.983	< 0.001^c
注：^a采用两独立样本t检验计算P值；^b采用χ²检验计算P值；^c采用Wilcoxon秩和检验计算P值。

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表 2 不同BMI孕妇的TMAO及其代谢产物水平比较[M(P₂₅, P₇₅)/n(%)]

Table 2. Levels of TMAO and its metabolites in pregnant women with different BMI [M(P₂₅, P₇₅)/n(%)]

TMAO及其代谢产物(nmol/ml)	BMI < 24.0 kg/m²	BMI≥24.0 kg/m²	χ²/z值	P值
TMAO	15.7(9.0, 22.5)	13.2(8.3, 21.8)	-1.332	0.183
< 22.3	239(74.7)	126(75.9)	0.086	0.769
≥22.3	81(25.3)	40(24.1)
胆碱	134.2(95.6, 184.9)	129.8(92.8, 184.7)	-0.114	0.909
< 184.7	240(75.0)	125(75.3)	0.005	0.942
≥184.7	80(25.0)	41(24.7)
甜菜碱	263.4(218.0, 324.8)	247.8(205.2, 306.5)	-2.189	0.029
< 318.5	233(72.8)	132(79.5)	2.628	0.105
≥318.5	87(27.2)	34(20.5)
肉碱	171.6(121.5, 225.8)	146.8(116.5, 203.4)	-1.807	0.071
< 224.4	236(73.7)	129(77.7)	0.917	0.338
≥224.4	84(26.3)	37(22.3)
TMA	147.0(81.3, 243.0)	181.7(102.3, 317.8)	-2.747	0.006
< 264.5	251(78.4)	114(68.7)	5.571	0.018
≥264.5	69(21.6)	52(31.3)

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表 3 TMAO及其代谢物与超重的关联分析

Table 3. Correlation analysis of TMAO and its metabolites with overweight

	β值	OR(95% CI)值	P值
模型1^a
TMAO	0.065	1.068(0.690~1.651)	0.769
胆碱	0.016	1.016(0.658~1.569)	0.942
甜菜碱	0.371	1.450(0.924~2.274)	0.106
肉碱	0.216	1.241(0.797~1.931)	0.339
TMA	0.572	1.771(1.193~2.629)	0.005
模型2^b
TMAO	0.009	1.009(0.586~1.739)	0.974
胆碱	-0.266	0.766(0.434~1.353)	0.359
甜菜碱	0.223	1.250(0.721~2.167)	0.427
肉碱	0.023	1.024(0.594~1.764)	0.933
TMA	0.590	1.803(1.118~2.907)	0.016
模型3^c
TMAO	0.021	1.021(0.586~1.780)	0.942
胆碱	-0.228	0.796(0.446~1.422)	0.442
甜菜碱	0.181	1.198(0.689~2.084)	0.522
肉碱	0.011	1.012(0.578~1.771)	0.968
TMA	0.550	1.734(1.063~2.827)	0.027
注：^a不调整混杂因素；^b调整教育水平、DBP、SBP、一级亲属糖尿病家族史、ALT；^c调整教育水平、DBP、SBP、一级亲属糖尿病家族史、ALT、孕早期FPG值。

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参考文献(19)

[1]	刘红宏, 胡晓敏, 田然, 等.肠道菌群及其代谢产物与动脉粥样硬化的研究进展[J].中国循环杂志, 2017, 32(12):1237-1239. DOI: 10.3969/j.issn.1000-3614.2017.12.025. Liu HH, Hu XM, Tian R, et al. Research progress of intestinal flora and its metabolites and atherosclerosis[J]. Chin Circul J, 2017, 32(12):1237-1239. DOI: 10.3969/j.issn.1000-3614.2017.12.025
[2]	Griffin JL, Wang X, Stanley E. Does our gut microbiome predict cardiovascular risk? A review of the evidence from metabolomics[J]. Circ Cardiovasc Genet, 2015, 8(1):187-191. DOI: 10.1161/CIRCGENETICS.114.000219.
[3]	Janeiro MH, Ramírez MJ, Milagro FI, et al. Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target[J]. Nutrients, 2018, 10(10):1398. DOI: 10.3390/nu10101398.
[4]	Tang WH, Hazen SL. Microbiome, trimethylamine N-oxide, and cardiometabolic disease[J]. Transl Res, 2017, 179:108-115. DOI: 10.1016/j.trsl.2016.07.007.
[5]	Huo X, Li J, Cao YF, et al. Trimethylamine N-oxide metabolites in early pregnancy and risk of gestational diabetes: a nested case-control study[J]. J Clin Endocrinol Metab, 2019, 104(11):5529-5539. DOI: 10.1210/jc.2019-00710.
[6]	Canyelles M, Tondo M, Cedó L, et al. Trimethylamine N-oxide: a link among diet, gut microbiota, gene regulation of liver and intestine cholesterol homeostasis and HDL function[J]. Int J Mol Sci, 2018, 19(10):3228. DOI: 10.3390/ijms19103228.
[7]	Dehghan P, Farhangi MA, Nikniaz L, et al. Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) potentially increases the risk of obesity in adults: an exploratory systematic review and dose-response meta-analysis[J]. Obes Rev, 2020, 21(5):e12993. DOI: 10.1111/obr.12993.
[8]	Schugar RC, Shih DM, Warrier M, et al. The TMAO-producing enzyme flavin-containing monooxygenase 3 regulates obesity and the beiging of white adipose tissue[J]. Cell Rep, 2017, 19(12):2451-2461. DOI: 10.1016/j.celrep.2017.05.077.
[9]	DiNicolantonio JJ, McCarty M, OKeefe J. Association of moderately elevated Tmethylamine-N-Oxide with cardiovascular risk: is TMAO serving as a marker for hepatic insulin resistance[J]. Open Heart, 2019, 6(1):e000890. DOI: 10.1136/openhrt-2018-000890.
[10]	Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease[J]. Nature, 2011, 472(7341):57-63. DOI: 10.1038/nature09922.
[11]	Inagaki T, Choi M, Moschetta A, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis[J]. Cell Metab, 2005, 2(4), 217-225. DOI: 10.1016/j.cmet.2005.09.001.
[12]	Bennett BJ, de Aguiar Vallim TQ, Wang Z, et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation[J]. Cell Metab, 2013, 17(1): 49-60. DOI: 10.1016/j.cmet.2012.12.011.
[13]	Zeisel SH, Warrier M. Trimethylamine N-oxide, the microbiome, and heart and kidney disease[J]. Annu Rev Nutr, 2017, 37:157-181. DOI: 10.1146/annurev-nutr-071816-064732.
[14]	Chávez-Talavera O, Tailleux A, Lefebvre P, et al. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease[J]. Gastroenterology, 2017, 152(7):1679-1694.e3. DOI: 10.1053/j.gastro.2017.01.055.
[15]	马少欣, 侯珊珊, 傅继华.肝脏糖脂代谢的胰岛素信号通路研究进展[J].药学研究, 2016, 35(2):94-96. DOI: 10.13506/j.cnki.jpr.2016.02.011. Ma SX, Hou SS, Fu JH. Research progress of the signaling pathway in sugar and lipid metabolism in hepatocyte[J]. Pharm Res, 2016, 35(2):94-96. DOI: 10.13506/j.cnki.jpr.2016.02.011.
[16]	Heianza Y, Sun D, Li X, et al. Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial[J]. Gut, 2019, 68(2):263-270. DOI: 10.1136/gutjnl-2018-316155.
[17]	Schönthal AH. Endoplasmic reticulum stress: its role in disease and novel prospects for therapy[J]. Scientifica (Cairo), 2012, 2012:857516. DOI: 10.6064/2012/857516.
[18]	Weyer C, Bogardus C, Mott DM, et al. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus[J]. J Clin Invest, 1999, 104(6):787-794. DOI: 10.1172/JCI7231.
[19]	Cnop M, Vidal J, Hull RL, et al. Progressive loss of β-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes[J]. Diabetes Care, 2007, 30(3):677-682. DOI: 10.2337/dc06-1834.

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变量	BMI < 24.0 kg/m²(n=320)	BMI≥24.0 kg/m²(n=166)	t/χ²/z值	P值
年龄(x±s, 岁)	29.0±2.9	29.6±3.2	-1.911	0.057^a
身高(x±s, cm)	163.2±4.8	163.0±4.7	0.496	0.620^a
体重(x±s, kg)	55.4±6.4	71.6±8.3	-23.797	< 0.001^a
BMI(x±s, kg/m²)	20.8±2.0	26.9±2.6	-29.073	< 0.001^a
孕周(x±s, 周)	10.1±2.0	10.2±2.2	-1.017	0.310^a
DBP(x±s, mmHg)	103.8±9.5	110.6±11.4	-6.999	< 0.001^a
SBP(x±s, mmHg)	67.8±7.2	72.0±8.6	-5.669	< 0.001^a
民族
汉族	310(96.9)	162(97.6)	0.026	0.872^b
其他民族	10(3.1)	4(2.4)
教育经历
受教育>12年	274(85.6)	125(75.3)	7.926	0.005^b
受教育≤12年	46(14.4)	41(24.7)
一级亲属糖尿病家族史
有	22(6.9)	22(13.3)	5.400	0.02^b
无	298(93.1)	144(86.7)
产次
＜1	303(94.7)	157(94.6)	0.003	0.960^b
≥1	17(5.3)	9(5.4)
既往吸烟
是	17(5.3)	11(6.6)	0.348	0.555^b
否	303(94.7)	155(93.4)
既往饮酒
是	87(27.2)	42(25.3)	0.199	0.655^b
否	233(72.8)	124(74.7)
孕早期FPG[M(P₂₅, P₇₅), mmol/L]	4.6(4.2, 5.0)	4.8(4.4, 5.2)	7.908	0.007^c
ALT [M(P₂₅, P₇₅), U/L]	16.0(11.0, 21.9)	19.0(13.0, 29.8)	-3.983	< 0.001^c
注：^a采用两独立样本t检验计算P值；^b采用χ²检验计算P值；^c采用Wilcoxon秩和检验计算P值。

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孕妇妊娠早期的氧化三甲胺及其代谢产物与超重的关联

doi: 10.16462/j.cnki.zhjbkz.2021.02.010

通讯作者:
霍晓旭，E-mail: huoxiaoxu@tmu.edu.cn

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Correlation analysis on trimethylamine N-oxide and its metabolites in early pregnancy with overweight

Corresponding author: HUO Xiao-xu, E-mail: huoxiaoxu@tmu.edu.cn

计量

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孕妇妊娠早期的氧化三甲胺及其代谢产物与超重的关联

doi: 10.16462/j.cnki.zhjbkz.2021.02.010

通讯作者: 霍晓旭，E-mail: huoxiaoxu@tmu.edu.cn

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出版历程

Correlation analysis on trimethylamine N-oxide and its metabolites in early pregnancy with overweight

Corresponding author: HUO Xiao-xu, E-mail: huoxiaoxu@tmu.edu.cn

计量

出版历程

目录

通讯作者:
霍晓旭，E-mail: huoxiaoxu@tmu.edu.cn