妊娠期糖尿病孕妇足月分娩新生儿的代谢特征

Metabolomics study on the newborns of pregnant women with gestational diabetes

目的探讨妊娠期糖尿病(gestational diabetes mellitus, GDM)孕妇与糖耐量正常孕妇新生儿脐带血的差异代谢物,分析GDM对新生儿代谢的影响。方法于2014—2016年在江苏省太仓地区招募孕早期孕妇参加队列研究,在孕24~28周通过口服糖耐量试验诊断GDM,以GDM孕妇为病例组,正常孕妇为对照组,随访孕妇至分娩,采集足月分娩新生儿的脐带血5 mL,利用超高效液相色谱-串联质谱法检测血清样本中非靶向代谢物。用T检验、主成分分析和正交偏最小二乘判别法分析两组脐带血的代谢物差异,根据P<0.05和变量重要度值(variable importance projection, VIP)>1.0筛选差异代谢物,基于KEGG数据库分析标志物涉及的代谢通路。结果根据GDM诊断结果纳入42名GDM孕妇和39名对照孕妇,脐带血样本中共检测出868种小分子代谢物,其中41种代谢物浓度存在组间差异(P<0.05且VIP>1.0),包括18种氨基酸类代谢物、9种脂类代谢物、5种外源性化合物、4种核苷酸类代谢物、3种多肽、1种维生素(泛酸)和1种辅酶(古洛糖酸)。γ-谷氨酰丙氨酸为GDM组低于对照组(P<0.01),其他化合物均为GDM组高于对照组(P<0.05)。结合通路分析,上述代谢物主要涉及赖氨酸降解途径和氨酰基tRNA生物合成途径。结论与血糖正常孕妇的新生儿相比,妊娠期糖尿病孕妇足月分娩新生儿的血液代谢物主要表现为部分氨基酸和脂类代谢物升高。

OBJECTIVE To investigate the metabolic changes of umbilical cord blood in pregnant women with gestational diabetes mellitus(GDM) compared with pregnant women with normal glucose tolerance, and to analyze the effect of GDM on neonatal metabolism. METHODS Pregnant women in the first trimester were recruited in the cohort study in Taicang District, Jiangsu Province from 2014 to 2016. Oral glucose tolerance test was used to diagnose GDM, at 24-28 weeks of gestation. Pregnant women with GDM were taken as the case group and normal pregnant women as the control group. Five mL of umbilical cord blood was collected from full-term newborns, and non-target metabolites in serum samples were detected by ultra high performance liquid chromatography-tandem mass spectrometry. The t test, principal component analysis and orthogonal partial least square analysis were used to analyze the difference of metabolites in umbilical cord blood between the two groups. The metabolic pathways involved in the markers were analyzed according to P<0.05 and variable importance projection(VIP)>1.0. The metabolic pathways involved in the markers were analyzed based on the KEGG database. RESULTS According to the result of GDM diagnosis, 42 pregnant women with GDM and 39 control pregnant women were included. A total of 868 small molecular metabolites were detected in umbilical cord blood samples. The concentrations of 41 metabolites were different between groups(P<0.05 and VIP>1.0), including 18 kinds of amino acid metabolites, 9 kinds of lipid metabolites, 5 kinds of exogenous compounds, 4 kinds of nucleotide metabolites, 3 kinds of peptides, 1 kind of vitamin(pantothenic acid) and 1 kind of coenzyme(gulonic acid). γ-glutamylalanine in the GDM group was lower than that in the control group(P<0.01), and other compounds in the GDM group were higher than those in the control group(P<0.05). Combined with pathway analysis, the above metabolites are mainly involved in lysine degradation pathway and aminoacyl tRNA biosynthesis pathway. CONCLUSION Compared with the newborns of pregnant women with normal blood glucose, the metabolites in cord serum from full-term newborns of pregnant women with GDM are mainly characterized by the increase of some amino acids and lipid metabolites.