Dudzik Danuta, Zorawski Marcin, Skotnicki Mariusz, Zarzycki Wieslaw, García Antonia, Angulo Santiago, Lorenzo M Paz, Barbas Coral, Ramos M Pilar
Center for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668, Madrid, Spain.
Department of Clinical Medicine, Faculty of Health Science, Medical University of Bialystok, 37 Szpitalna Street, 15-254, Bialystok, Poland.
J Pharm Biomed Anal. 2017 Sep 10;144:90-98. doi: 10.1016/j.jpba.2017.02.056. Epub 2017 Mar 1.
Gestational Diabetes Mellitus (GDM) causes severe short- and long-term complications for the mother, fetus and neonate, including type 2-diabetes (T2DM) later in life. In this pilot study, GC-Q/MS analysis was applied for plasma metabolomics fingerprinting of 24 healthy and 24 women with GDM at different stages of gestation (second and third trimester) and postpartum (one and three months). Multivariate (unsupervised and supervised) statistical analysis was performed to investigate variance in the data, identify outliers and for unbiased assessment of data quality. Plasma fingerprints allowed for the discrimination of GDM pregnant women from controls both in the 2nd and 3rd trimesters of gestation. However, metabolic profiles tended to be similar after delivery. Follow up of these women revealed that 4 of them developed T2DM within 2 years postpartum. Multivariate PLS-DA models limited to women with GDM showed clear separation 3 months postpartum. In the 2nd trimester of gestation there was also a clear separation between GDM women that were normoglycemic after pregnancy and those with recognized postpartum T2DM. Metabolites that had the strongest discriminative power between these groups in the 2nd trimester of gestation were 2-hydroxybutyrate, 3-hydroxybutyrate, and stearic acid. We have described, that early GDM comprises metabotypes that are associated with the risk of future complications, including postpartum T2DM. In this pilot study, we provide evidence that 2-hydroxybutyrate and 3-hydroxybutyrate may be considered as future prognostic biomarkers to predict the onset of diabetic complications in women with gestational diabetes after delivery.
妊娠期糖尿病（GDM）会给母亲、胎儿和新生儿带来严重的短期和长期并发症，包括日后患2型糖尿病（T2DM）。在这项初步研究中，气相色谱-质谱联用（GC-Q/MS）分析被用于对24名健康女性以及24名患有GDM的女性在妊娠不同阶段（孕中期和孕晚期）及产后（产后1个月和3个月）的血浆代谢组学进行指纹图谱分析。进行了多变量（无监督和有监督）统计分析，以研究数据中的差异、识别异常值并对数据质量进行无偏评估。血浆指纹图谱能够区分孕中期和孕晚期患有GDM的孕妇与对照组。然而，产后的代谢谱趋于相似。对这些女性的随访显示，其中4人在产后2年内患上了T2DM。限于患有GDM的女性的多变量偏最小二乘判别分析（PLS-DA）模型在产后3个月显示出明显的区分。在孕中期，妊娠后血糖正常的GDM女性与产后被诊断为T2DM的女性之间也有明显区分。在孕中期，这些组之间具有最强判别能力的代谢物是2-羟基丁酸、3-羟基丁酸和硬脂酸。我们已经描述过，早期GDM包含与未来并发症风险相关的代谢型，包括产后T2DM。在这项初步研究中，我们提供了证据表明，2-羟基丁酸和3-羟基丁酸可能被视为未来的预后生物标志物，以预测妊娠期糖尿病女性产后糖尿病并发症的发生。
