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On-line Access: 2021-03-12

Received: 2020-08-18

Revision Accepted: 2021-01-03

Crosschecked: 2021-02-22

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 ORCID:

Dajing XIA

https://orcid.org/0000-0003-1645-9046

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.3 P.223-232

http://doi.org/10.1631/jzus.B2000483


Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus


Author(s):  Bo ZHU, Zhixin MA, Yuning ZHU, Lei FANG, Hong ZHANG, Hongwei KONG, Dajing XIA

Affiliation(s):  Department of Laboratorial Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; more

Corresponding email(s):   dxia@zju.edu.cn

Key Words:  Gestational diabetes mellitus (GDM), Bile acid, Insulin resistance, &beta, -Cell compensation


Bo ZHU, Zhixin MA, Yuning ZHU, Lei FANG, Hong ZHANG, Hongwei KONG, Dajing XIA. Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus[J]. Journal of Zhejiang University Science B, 2021, 22(3): 223-232.

@article{title="Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus",
author="Bo ZHU, Zhixin MA, Yuning ZHU, Lei FANG, Hong ZHANG, Hongwei KONG, Dajing XIA",
journal="Journal of Zhejiang University Science B",
volume="22",
number="3",
pages="223-232",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000483"
}

%0 Journal Article
%T Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus
%A Bo ZHU
%A Zhixin MA
%A Yuning ZHU
%A Lei FANG
%A Hong ZHANG
%A Hongwei KONG
%A Dajing XIA
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 3
%P 223-232
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000483

TY - JOUR
T1 - Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus
A1 - Bo ZHU
A1 - Zhixin MA
A1 - Yuning ZHU
A1 - Lei FANG
A1 - Hong ZHANG
A1 - Hongwei KONG
A1 - Dajing XIA
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 3
SP - 223
EP - 232
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000483


Abstract: 
gestational diabetes mellitus (GDM) is characterized by glycemia and insulin disorders. bile acids (BAs) have emerged as vital signaling molecules in glucose metabolic regulation. BA change in GDM is still unclear, which exerts great significance to illustrate the change of BAs in GDM. GDM patients and normal pregnant women were enrolled during the oral glucose tolerance test (OGTT) screening period. Fasting serums were sampled for the measurement of BAs. BA metabolism profiles were analyzed in both pregnant women with GDM and those with normal glucose tolerance (NGT). Delivery characteristics, delivery gestational age, and infant birthweight were extracted from medical records. GDM patients presented distinctive features compared with NGT patients, including higher body mass index (BMI), elevated serum glucose concentration, raised insulin (both fasting and OGTT), and increased hemoglobin A1c (HbA1c) levels. Higher homeostasis model assessment of insulin resistance (HOMA-IR) and decreased &beta;-Cell compensation (i.e., oral disposition index (DIo)) were also prevalent in this group. Total BAs (TBAs) remained stable, but glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) levels declined significantly in GDM. GDCA was inversely correlated with HOMA-IR and positively correlated with DIo. No obvious differences in clinical outcome between the GDM and NGT groups were observed. However, GDM patients with high HOMA-IR and low DIo tended to have a higher cesarean delivery rate and younger delivery gestational age. In conclusion, GDCA provides a valuable biomarker to evaluate HOMA-IR and DIo, and decreased GDCA levels predict poorer clinical outcomes for GDM.

妊娠期糖尿病患者血清中甘氨酸结合型脱氧胆酸降低与不良妊娠结局的相关性

目的:探讨胆汁酸代谢异常与妊娠期糖尿病不良妊娠结局的相关性。
创新点:首次利用高效液相色谱串联质谱(LC-MS)方法检测到妊娠期糖尿病(GDM)患者在口服糖耐量(OGTT)筛查期间血清胆汁酸谱的异常改变,通过结合差异性胆汁酸谱和GDM患者的分娩方式和分娩孕周及胎儿出生体重,以期为预测GDM所致的不良妊娠结局提供科学依据。
方法:本研究对浙江大学医学院附属妇产科医院2019年5月至2019年10月筛查到的GDM患者进行了回顾性分析,根据国际糖尿病与妊娠研究组公布的GDM诊断标准纳入OGTT筛查期间GDM患者67名,正常妊娠对照组48名。收集研究对象空腹状态及服糖后1、2小时的血清,检测血糖及胰岛素水平,计算GDM患者和对照组胰岛素抵抗指数(HOMA-IR)、胰岛细胞功能指数(HOMA-β)、胰岛素分泌指数、胰岛素敏感性指数,用胰岛素分泌指数(Stumvoll ?rst-phase estimate)×胰岛素敏感性指数计算β细胞补偿功能(DIo),同时利用LC-MS检测研究对象的空腹胆汁酸代谢谱,研究胆汁酸代谢的改变与上述指标之间的相关性。收集两组人群的临床资料包括基本资料及分娩方式、分娩孕周和胎儿出生体重,分析差异性胆汁酸与不良妊娠结局的相关性。
结论:甘氨酸结合型脱氧胆酸(GDCA)可作为评估HOMA-IR和DIo的有效指标,同时GDCA降低可提示GDM患者不良妊娠结局。

关键词:妊娠期糖尿病;胆汁酸;胰岛素抵抗;β细胞补偿功能

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BellafanteE, McilvrideS, NikolovaV, et al., 2020. Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis. Sci Rep, 10:11523.

[2]CariouB, van HarmelenK, Duran-SandovalD, et al., 2006. The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice. J Biol Chem, 281(16):11039-11049.

[3]di CianniG, MiccoliR, VolpeL, et al., 2003. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev, 19(4):259-270.

[4]Duran-SandovalD, CariouB, PercevaultF, et al., 2005. The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition. J Biol Chem, 280(33):29971-29979.

[5]ElbeinSC, WegnerK, KahnSE, 2000. Reduced beta-cell compensation to the insulin resistance associated with obesity in members of caucasian familial type 2 diabetic kindreds. Diabetes Care, 23(2):221-227.

[6]HaeuslerRA, Pratt-HyattM, WelchCL, et al., 2012. Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metab, 15(1):65-74.

[7]HaeuslerRA, AstiarragaB, CamastraS, et al., 2013. Human insulin resistance is associated with increased plasma levels of 12α-hydroxylated bile acids. Diabetes, 62(12):4184-4191.

[8]The HAPO Study Cooperative Research Group, 2009. Hyperglycemia and adverse pregnancy outcome (HAPO) study: associations with neonatal anthropometrics. Diabetes, 58(2):453-459.

[9]HaslamDE, LiJ, LiangLM, et al., 2020. Changes in metabolites during an oral glucose tolerance test in early and mid-pregnancy: findings from the pearls randomized, controlled lifestyle trial. Metabolites, 10(7):284.

[10]HouWL, MengXY, ZhaoWJ, et al., 2016. Elevated first-trimester total bile acid is associated with the risk of subsequent gestational diabetes. Sci Rep, 6:34070.

[11]HouWL, MengXY, ZhaoAH, et al., 2018. Development of multimarker diagnostic models from metabolomics analysis for gestational diabetes mellitus (GDM). Mol Cell Proteomics, 17(3):431-441.

[12]Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group, 2010. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol, 202(3):255.e1-255.e7.

[13]JiaET, LiuZY, PanM, et al., 2019. Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(10):781-792.

[14]JinLH, FangZP, FanMJ, et al., 2019. Bile-ology: from bench to bedside. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(5):414-427.

[15]JohnsEC, DenisonFC, NormanJE, et al., 2018. Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab, 29(11):743-754.

[16]KatsumaS, HirasawaA, TsujimotoG, 2005. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun, 329(1):386-390.

[17]KimH, FangS, 2018. Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis. Lab Anim Res, 34(4):140-146.

[18]KongM, LuZ, ZhongC, et al., 2020. A higher level of total bile acid in early mid-pregnancy is associated with an increased risk of gestational diabetes mellitus: a prospective cohort study in Wuhan, China. J Endocrinol Invest, 43(8):1097-1103.

[19]LiJ, HuoXX, CaoYF, et al., 2018. Bile acid metabolites in early pregnancy and risk of gestational diabetes in Chinese women: a nested case-control study. EBioMedicine, 35:317-324.

[20]MartineauMG, RakerC, DixonPH, et al., 2015. The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. Diabetes Care, 38(2):243-248.

[21]MatsudaM, DeFronzoRA, 1999. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care, 22(9):1462-1470.

[22]MoghettiP, TosiF, 2021. Insulin resistance and PCOS: chicken or egg? J Endocrinol Invest, 44(2):233-244.

[23]MollU, Landin-OlssonM, NilssonC, et al., 2020. Pregnancy outcome in women with gestational diabetes—a longitudinal study of changes in demography and treatment modalities. Acta Obstet Gynecol Scand, 99(3):333-340.

[24]MortierI, BlancJ, ToselloB, et al., 2017. Is gestational diabetes an independent risk factor of neonatal severe respiratory distress syndrome after 34 weeks of gestation? A prospective study. Arch Gynecol Obstet, 296(6):1071-1077.

[25]O'SullivanEP, AvalosG, O'ReillyMW, et al., 2011. Atlantic diabetes in pregnancy (DIP): the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. Diabetologia, 54(7):1670-1675.

[26]PotthoffMJ, Boney-MontoyaJ, ChoiM, et al., 2011. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathway. Cell Metab, 13(6):729-738.

[27]QiXY, YunCY, SunLL, et al., 2019. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med, 25(8):1225-1233.

[28]ShapiroH, KolodziejczykAA, HalstuchD, et al., 2018. Bile acids in glucose metabolism in health and disease. J Exp Med, 215(2):383-396.

[29]StumvollM, MitrakouA, PimentaW, et al., 2000. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care, 23(3):295-301.

[30]StumvollM, van HaeftenT, FritscheA, et al., 2001. Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care, 24(4):796-797.

[31]TrabelsiMS, DaoudiM, PrawittJ, et al., 2015. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun, 6:7629.

[32]van NieropFS, MeessenECE, NelissenKGM, et al., 2019. Differential effects of a 40-hour fast and bile acid supplementation on human GLP-1 and FGF19 responses. Am J Physiol Endocrinol Metab, 317(3):E494-E502.

[33]WangJ, LiZ, LinL, 2019. Maternal lipid profiles in women with and without gestational diabetes mellitus. Medicine, 98(16):e15320.

[34]WatanabeM, HoutenSM, WangL, et al., 2004. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest, 113(10):1408-1418.

[35]WeiYM, YangHX, ZhuWW, et al., 2017. Adverse pregnancy outcome among women with pre-gestational diabetes mellitus: a population-based multi-centric study in Beijing. J Matern Fetal Neonatal Med, 30(20):2395-2397.

[36]WeinertLS, 2010. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy: comment to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel. Diabetes Care, 33(7):e97.

[37]ZhangQ, BaoZK, DengMX, et al., 2020. Fetal growth, fetal development, and placental features in women with polycystic ovary syndrome: analysis based on fetal and placental magnetic resonance imaging. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(12):977-989.

[38]ZhangYQ, GeXM, HeemstraLA, et al., 2012. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice. Mol Endocrinol, 26(2):272-280.

[39]ZhouX, LiJQ, WeiLJ, et al., 2020. Silencing of DsbA-L gene impairs the PPARγ agonist function of improving insulin resistance in a high-glucose cell model. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(12):990-998.

[40]ZhuB, YinPY, MaZX, et al., 2019. Characteristics of bile acids metabolism profile in the second and third trimesters of normal pregnancy. Metabolism, 95:77-83.

[41]ZhuW, WangSY, DaiHJ, et al., 2020. Serum total bile acids associate with risk of incident type 2 diabetes and longitudinal changes in glucose-related metabolic traits. J Diabetes, 12(8):616-625.

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