Frankevich Natalia A, Tokareva Alisa O, Yuriev Sergey Yu, Chagovets Vitaly V, Kutsenko Anastasia A, Novoselova Anastasia V, Karapetian Tamara E, Lagutin Vadim V, Frankevich Vladimir E, Sukhikh Gennady T
National Medical Research Center for Obstetrics Gynecology and Perinatology Named After Academician V.I. Kulakov, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia.
Department of Obstetrics and Gynecology, Siberian State Medical University, 634050 Tomsk, Russia.
Int J Mol Sci. 2025 Aug 28;26(17):8351. doi: 10.3390/ijms26178351.
Gestational diabetes mellitus (GDM) is a growing global health concern, driving the need for novel diagnostic and prognostic approaches. The aim of this study was to analyze the amino acid profile in the mother-fetus system (maternal venous blood, umbilical cord blood, and amniotic fluid) and to identify specific biological markers of GDM and macrosomia. Using HPLC-MS/MS, we analyzed serum from maternal venous and umbilical cord blood, along with amniotic fluid, across 94 mother-fetus pairs (53 GDM, 41 controls). Machine learning and metabolic pathway analysis revealed significant alterations in 19 amino acids. In GDM, maternal serum showed elevated 5-OH-lysine and homocitrulline, while cord blood had higher isoleucine, serine, and threonine. Amniotic fluid exhibited increased leucine, isoleucine, threonine, serine, arginine, and ornithine. Conversely, histidine, glutamine, alanine, asparagine, β-/γ-aminobutyric acids, phenylalanine, ornithine, and citrulline were reduced. Histidine, glutamine, and asparagine inversely correlated with blood glucose (r = -0.26, r = -0.33, r = -0.30) and were lower in GDM. These findings highlight three key metabolic loci in GDM pathogenesis, with glutamine, histidine, and asparagine emerging as potential maternal blood biomarkers for early macrosomia prediction. However, given confounding factors in metabolomic studies, further large-scale validation is essential.
妊娠期糖尿病（GDM）是一个日益受到全球关注的健康问题，这促使人们需要新的诊断和预后方法。本研究的目的是分析母胎系统（母体静脉血、脐带血和羊水）中的氨基酸谱，并确定GDM和巨大儿的特定生物标志物。我们使用高效液相色谱-串联质谱法（HPLC-MS/MS）分析了94对母婴（53例GDM患者，41例对照）的母体静脉血、脐带血血清以及羊水。机器学习和代谢途径分析显示19种氨基酸有显著变化。在GDM患者中，母体血清中5-羟基赖氨酸和高瓜氨酸升高，而脐带血中异亮氨酸、丝氨酸和苏氨酸含量更高。羊水中亮氨酸、异亮氨酸、苏氨酸、丝氨酸、精氨酸和鸟氨酸增加。相反，组氨酸、谷氨酰胺、丙氨酸、天冬酰胺、β-/γ-氨基丁酸、苯丙氨酸、鸟氨酸和瓜氨酸减少。组氨酸、谷氨酰胺和天冬酰胺与血糖呈负相关（r = -0.26，r = -0.33，r = -0.30），且在GDM患者中含量较低。这些发现突出了GDM发病机制中的三个关键代谢位点，谷氨酰胺、组氨酸和天冬酰胺有望成为预测早期巨大儿的母体血液生物标志物。然而，鉴于代谢组学研究中的混杂因素，进一步的大规模验证至关重要。
