Diboun Ilhame, Ramanjaneya Manjunath, Majeed Yasser, Ahmed Lina, Bashir Mohammed, Butler Alexandra E, Abou-Samra Abdul Badi, Atkin Stephen L, Mazloum Nayef A, Elrayess Mohamed A
Hamad Bin Khalifa University (HBKU), Doha, Qatar.
Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar.
J Transl Med. 2020 Sep 24;18(1):366. doi: 10.1186/s12967-020-02531-5.
Pregnant women with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM) are at increased risks of pre-term labor, hypertension and preeclampsia. In this study, metabolic profiling of blood samples collected from GDM, T2DM and control pregnant women was undertaken to identify potential diagnostic biomarkers in GDM/T2DM and compared to pregnancy outcome.
Sixty-seven pregnant women (21 controls, 32 GDM, 14 T2DM) in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP Quant 500 Kit. Linear regression models were used to identify the metabolic signature of GDM and T2DM, followed by generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine best predictors of GDM, T2DM and pre-term labor.
The gestational age at delivery was 2 weeks earlier in T2DM compared to GDM and controls and correlated negatively with maternal HbA1C and systolic blood pressure and positively with serum albumin. Linear regression models revealed elevated glutamate and branched chain amino acids in GDM + T2DM group compared to controls. Regression models also revealed association of lower levels of triacylglycerols and diacylglycerols containing oleic and linoleic fatty acids with pre-term delivery. A generalized linear model ROC analyses revealed that that glutamate is the best predictors of GDM compared to controls (area under curve; AUC = 0.81). The model also revealed that phosphatidylcholine diacyl C40:2, arachidonic acid, glycochenodeoxycholic acid, and phosphatidylcholine acyl-alkyl C34:3 are the best predictors of GDM + T2DM compared to controls (AUC = 0.90). The model also revealed that the triacylglycerols C17:2/36:4 and C18:1/34:1 are the best predictors of pre-term delivery (≤ 37 weeks) (AUC = 0.84).
This study highlights the metabolite alterations in women in their second trimester with diabetes mellitus and identifies predictive indicators of pre-term delivery. Future studies to confirm these associations in other cohorts and investigate their functional relevance and potential utilization for targeted therapies are warranted.
患有妊娠期糖尿病（GDM）或2型糖尿病（T2DM）的孕妇发生早产、高血压和先兆子痫的风险增加。在本研究中，对从GDM、T2DM孕妇及对照孕妇采集的血样进行代谢谱分析，以识别GDM/T2DM潜在的诊断生物标志物，并与妊娠结局进行比较。
67名处于孕中期的孕妇（21名对照、32名GDM患者、14名T2DM患者）使用Biocrates MxP Quant 500试剂盒通过串联质谱对血浆样本进行靶向代谢组学分析。使用线性回归模型识别GDM和T2DM的代谢特征，随后进行广义线性模型（GLMNET）和受试者工作特征（ROC）分析，以确定GDM、T2DM和早产的最佳预测指标。
与GDM患者和对照相比，T2DM患者的分娩孕周提前2周，且与孕妇糖化血红蛋白（HbA1C）和收缩压呈负相关，与血清白蛋白呈正相关。线性回归模型显示，与对照相比，GDM+T2DM组的谷氨酸和支链氨基酸水平升高。回归模型还显示，含有油酸和亚油酸的甘油三酯和甘油二酯水平较低与早产有关。广义线性模型ROC分析显示，与对照相比，谷氨酸是GDM的最佳预测指标（曲线下面积；AUC=0.81）。该模型还显示，与对照相比，磷脂酰胆碱二酰基C40:2、花生四烯酸、甘氨鹅脱氧胆酸和磷脂酰胆碱酰基-烷基C34:3是GDM+T2DM的最佳预测指标（AUC=0.90）。该模型还显示，甘油三酯C17:2/36:4和C18:1/34:1是早产（≤37周）的最佳预测指标（AUC=0.84）。
本研究突出了孕中期糖尿病女性体内的代谢物变化，并确定了早产的预测指标。有必要开展进一步研究，在其他队列中证实这些关联，并研究其功能相关性以及在靶向治疗中的潜在应用价值。
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