妊娠期糖尿病患者不同孕期肠道微生物和代谢产物水平变化与胰岛素抵抗的关系

doi:10.11958/20221614

天津医药 ›› 2023, Vol. 51 ›› Issue (6): 624-627.doi: 10.11958/20221614

妊娠期糖尿病患者不同孕期肠道微生物和代谢产物水平变化与胰岛素抵抗的关系

祝淑平¹(), 马丽¹, 叶晓林¹, 顾俊菲²^,^△

1 安徽医科大学附属安庆市第一人民医院妇产科（邮编246000）
2 皖南医学院第二附属医院妇产科

收稿日期:2022-10-08 修回日期:2022-12-25 出版日期:2023-06-15 发布日期:2023-06-20
通讯作者: ^△E-mail：gujf1988@126.com
作者简介:祝淑平（1977），女，副主任医师，主要从事妊娠期糖尿病的诊断和治疗方面研究。E-mail：zsp1977ah@163.com
基金资助:
安徽省卫生健康委科研项目(AHWJ2021a003)

Relationship between changes of gut microbes and metabolite levels and insulin resistance in patients with gestational diabetes mellitus at different stages of pregnancy

ZHU Shuping¹(), MA Li¹, YE Xiaolin¹, GU Junfei²^,^△

1 Department of Obstetrics and Gynecology, Anqing First People's Hospital Affiliated to Anhui Medical University, Anqing 246000, China
2 Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wannan Medical College

Received:2022-10-08 Revised:2022-12-25 Published:2023-06-15 Online:2023-06-20
Contact: ^△E-mail：gujf1988@126.com

祝淑平, 马丽, 叶晓林, 顾俊菲. 妊娠期糖尿病患者不同孕期肠道微生物和代谢产物水平变化与胰岛素抵抗的关系[J]. 天津医药, 2023, 51(6): 624-627.

ZHU Shuping, MA Li, YE Xiaolin, GU Junfei. Relationship between changes of gut microbes and metabolite levels and insulin resistance in patients with gestational diabetes mellitus at different stages of pregnancy[J]. Tianjin Medical Journal, 2023, 51(6): 624-627.

摘要/Abstract

摘要：

目的探讨妊娠期糖尿病（GDM）患者不同孕期肠道微生物和代谢产物水平变化及与胰岛素抵抗（IR）的关系。方法选取在安徽医科大学附属安庆市第一人民医院进行产检并计划在本院生产的120例GDM孕妇。分别于孕早期、孕中期、孕晚期采集粪便中段样本，应用16S rRNA法测定生物菌群分布以分析肠道微生物情况；采用液相色谱-串联质谱法检测粪便样本中氧化三甲胺（TMAO）及相关代谢产物；采用稳态模型计算胰岛素抵抗指数（HOMA-IR）和稳态模型评估β细胞功能指数（HOMA-β），并分析不同孕期肠道微生物和代谢产物水平变化及与IR的关系。结果孕早、中、晚期肠道拟杆菌属、栖粪杆菌属丰度依次降低，厚壁菌属、放线菌属丰度依次升高（P<0.05）；孕早、中、晚期GDM患者肠道TMAO、TMA水平依次升高（P<0.05）；孕早、中、晚期患者HOMA-IR依次升高，HOMA-β依次下降（P<0.05）；拟杆菌属、栖粪杆菌属与HOMA-IR呈负相关，与HOMA-β呈正相关（P<0.05）；厚壁菌属、放线菌属、TMAO、TMA与HOMA-IR呈正相关，与HOMA-β呈负关（P<0.05）。结论随着孕期进展，GDM患者肠道微生物及代谢产物水平紊乱会增加IR的发生风险。

关键词: 糖尿病, 妊娠, 胃肠道微生物组, 胰岛素抵抗, 孕期

Abstract:

Objective To investigate changes of gut microbes and metabolites in patients with gestational diabetes mellitus (GDM) at different stages of pregnancy, and their relationship with insulin resistance (IR). Methods A total of 120 pregnant women with GDM who underwent prenatal examination in Anqing First People's Hospital affiliated to Anhui Medical University and plan to produce in this hospital were included in this study. Fecal samples in the first, second and third trimester of pregnancy were collected respectively. 16S rRNA method was used to determine the distribution of biological flora and to analyze the intestinal microbial situation. Liquid chromatography-tandem mass spectrometry was used to detect trimethylamine oxide (TMAO) and related metabolites in fecal samples. Insulin resistance index (HOMA-IR) was calculated sing steady-state model, and steady-state model β cell function index (HOMA-β) was evaluated. Changes of intestinal microorganism and metabolite levels in different pregnancy stages and their relationship with insulin resistance were analyzed. Results The abundance of Bacteroides and Faecalibacterium decreased in order, while the abundance of Firmicutes and Actinobacteria increased in order from the first trimester, the second trimester to the third trimester (P<0.05). TMAO, TMA and HOMA-IR increased in order, while HOMA-beta decreased in order from the first trimester, the second trimester to the third trimester (P<0.05). In the third trimester of pregnancy, Bacteroides and Faecalibacterium were negatively correlated with HOMA-IR and positively correlated with HOMA-β (P<0.05). Firmicutes, Actinomycetes, TMAO and TMA were positively correlated with HOMA-IR and negatively correlated with HOMA-β (P<0.05). Conclusion With the progress of pregnancy, the disturbance of intestinal microorganisms and metabolites in pregnant women with GDM increases the risk of developing IR.

Key words: diabetes, gestational, gastrointestinal microbiome, insulin resistance, pregnancy periods

中图分类号:

R714.147

图/表 3

参考文献 24

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孕期		拟杆菌属		普氏菌属		另枝菌属	栖粪杆菌属		考拉杆菌属
孕早期		35.25±3.64		6.11±0.63		2.43±0.22	11.69±1.42		8.47±0.85
孕中期		27.58±3.14^a		6.12±0.78		2.46±0.28	9.71±0.98^a		8.66±0.87
孕晚期		25.69±5.24^ab		6.19±0.81		2.47±0.39	6.75±0.71^ab		8.59±0.82
F		182.485^＊＊		0.412		0.094	639.242^＊＊		1.545
孕期	毛螺菌属		副杆菌属		布劳特氏菌属			厚壁菌属	放线菌属
孕早期	4.83±0.45		1.13±0.12		0.35±0.07			2.36±0.45	9.05±2.01
孕中期	4.87±0.52		1.12±0.17		0.34±0.07			3.16±0.38^a	10.36±1.58^a
孕晚期	4.92±0.71		1.15±0.18		0.33±0.07			4.17±0.48^ab	13.26±1.54^ab
F	0.749		1.110		2.449			513.03^＊＊	187.583^＊＊

孕期		拟杆菌属		普氏菌属		另枝菌属	栖粪杆菌属		考拉杆菌属
孕早期		35.25±3.64		6.11±0.63		2.43±0.22	11.69±1.42		8.47±0.85
孕中期		27.58±3.14^a		6.12±0.78		2.46±0.28	9.71±0.98^a		8.66±0.87
孕晚期		25.69±5.24^ab		6.19±0.81		2.47±0.39	6.75±0.71^ab		8.59±0.82
F		182.485^＊＊		0.412		0.094	639.242^＊＊		1.545
孕期	毛螺菌属		副杆菌属		布劳特氏菌属			厚壁菌属	放线菌属
孕早期	4.83±0.45		1.13±0.12		0.35±0.07			2.36±0.45	9.05±2.01
孕中期	4.87±0.52		1.12±0.17		0.34±0.07			3.16±0.38^a	10.36±1.58^a
孕晚期	4.92±0.71		1.15±0.18		0.33±0.07			4.17±0.48^ab	13.26±1.54^ab
F	0.749		1.110		2.449			513.03^＊＊	187.583^＊＊

孕期	TMAO	TMA	左旋肉碱	氯化胆碱	甜菜碱
孕早期	8.26±2.35	181.23±19.58	122.36±25.29	113.26±25.87	225.36±37.21
孕中期	10.58±2.71^a	234.16±30.15^a	120.54±27.21	120.37±25.69	226.47±38.45
孕晚期	12.36±2.54^ab	297.41±30.29^ab	127.36±26.57	119.64±29.33	231.36±35.47
F	78.768^＊＊	551.159^＊＊	2.152	2.515	0.890

孕期	TMAO	TMA	左旋肉碱	氯化胆碱	甜菜碱
孕早期	8.26±2.35	181.23±19.58	122.36±25.29	113.26±25.87	225.36±37.21
孕中期	10.58±2.71^a	234.16±30.15^a	120.54±27.21	120.37±25.69	226.47±38.45
孕晚期	12.36±2.54^ab	297.41±30.29^ab	127.36±26.57	119.64±29.33	231.36±35.47
F	78.768^＊＊	551.159^＊＊	2.152	2.515	0.890

孕期	HOMA-IR	HOMA-β
孕早期	1.25±0.23	67.25±7.19
孕中期	1.69±0.17^a	36.54±5.44^a
孕晚期	3.58±0.39^ab	21.36±3.58^ab
F	2 358.598^＊＊	2 090.892^＊＊

妊娠期糖尿病患者不同孕期肠道微生物和代谢产物水平变化与胰岛素抵抗的关系

Relationship between changes of gut microbes and metabolite levels and insulin resistance in patients with gestational diabetes mellitus at different stages of pregnancy

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