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妊娠期糖尿病的代谢指纹图谱。

Metabolic fingerprint of Gestational Diabetes Mellitus.

作者信息

Dudzik Danuta, Zorawski Marcin, Skotnicki Mariusz, Zarzycki Wieslaw, Kozlowska Gabryela, Bibik-Malinowska Katarzyna, Vallejo María, García Antonia, Barbas Coral, Ramos M Pilar

机构信息

CEMBIO (Center for Metabolomics and Bioanalysis), Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain; Department of Pharmacology, Medical University of Bialystok, Bialystok, Poland.

Department of Pharmacology, Medical University of Bialystok, Bialystok, Poland.

出版信息

J Proteomics. 2014 May 30;103:57-71. doi: 10.1016/j.jprot.2014.03.025. Epub 2014 Mar 31.

Abstract

UNLABELLED

Gestational Diabetes (GDM) is causing severe short- and long-term complications for mother, fetus or neonate. As yet, the metabolic alterations that are specific for the development of GDM have not been fully determined, which also precludes the early diagnosis and prognosis of this pathology. In this pilot study, we determine the metabolic fingerprint, using a multiplatform LC-QTOF/MS, GC-Q/MS and CE-TOF/MS system, of plasma and urine samples of 20 women with GDM and 20 with normal glucose tolerance in the second trimester of pregnancy. Plasma fingerprints allowed for the discrimination of GDM pregnant women from controls. In particular, lysoglycerophospholipids showed a close association with the glycemic state of the women. In addition, we identified some metabolites with a strong discriminative power, such as LPE(20:1), (20:2), (22:4); LPC(18:2), (20:4), (20:5); LPI(18:2), (20:4); LPS(20:0) and LPA(18:2), as well as taurine-bile acids and long-chain polyunsaturated fatty acid derivatives. Finally, we provide evidence for the implication of these compounds in metabolic routes, indicative of low-grade inflammation and altered redox-balance, that may be related with the specific pathophysiological context of the genesis of GDM. This highlights their potential use as prognostic markers for the identification of women at risk to develop severe glucose intolerance during pregnancy.

BIOLOGICAL SIGNIFICANCE

Gestational Diabetes Mellitus (GDM) is increasing worldwide and, although diabetes usually remits after pregnancy, women with GDM have a high risk of developing postpartum type 2-diabetes, particularly when accompanied by obesity. Therefore, understanding the pathophysiology of GDM, as well as the identification of potentially modifiable risk factors and early diagnostic markers for GDM are relevant issues. In the present study, we devised a multiplatform metabolic fingerprinting approach to obtain a comprehensive picture of the early metabolic alternations that occur in GDM, and may reflect on the specific pathophysiological context of the disease. Future studies at later stages of gestation will allow us to validate the discriminant power of the identified metabolites.

摘要

未标注

妊娠期糖尿病(GDM)正在给母亲、胎儿或新生儿带来严重的短期和长期并发症。迄今为止,GDM发生发展所特有的代谢改变尚未完全明确,这也妨碍了对该病症的早期诊断和预后评估。在这项初步研究中,我们使用多平台液相色谱-四极杆飞行时间质谱(LC-QTOF/MS)、气相色谱-质谱联用(GC-Q/MS)和毛细管电泳-飞行时间质谱(CE-TOF/MS)系统,测定了20例妊娠期糖尿病女性和20例孕中期糖耐量正常女性的血浆和尿液样本的代谢指纹图谱。血浆指纹图谱能够区分妊娠期糖尿病孕妇和对照组。特别是,溶血甘油磷脂与女性的血糖状态密切相关。此外,我们还鉴定出一些具有强大鉴别能力的代谢物,如溶血磷脂酰乙醇胺(LPE)(20:1)、(20:2)、(22:4);溶血磷脂酰胆碱(LPC)(18:2)、(20:4)、(20:5);溶血磷脂酰肌醇(LPI)(18:2)、(20:4);溶血磷脂酰丝氨酸(LPS)(20:0)和溶血磷脂酸(LPA)(18:2),以及牛磺酸结合胆汁酸和长链多不饱和脂肪酸衍生物。最后,我们提供证据表明这些化合物参与了代谢途径,提示存在低度炎症和氧化还原平衡改变,这可能与GDM发生的特定病理生理背景有关。这突出了它们作为预后标志物的潜在用途,可用于识别孕期有发生严重糖耐量异常风险的女性。

生物学意义

妊娠期糖尿病(GDM)在全球范围内呈上升趋势,尽管糖尿病通常在产后缓解,但患有GDM的女性患产后2型糖尿病的风险很高,尤其是伴有肥胖时。因此,了解GDM的病理生理学,以及识别潜在可改变的风险因素和GDM的早期诊断标志物是相关的重要问题。在本研究中,我们设计了一种多平台代谢指纹图谱方法,以全面了解GDM中发生的早期代谢变化,并可能反映该疾病的特定病理生理背景。未来在妊娠后期进行的研究将使我们能够验证所鉴定代谢物的鉴别能力。

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