Farkas Anna, Suranyi Andrea, Kolcsar Balint, Gyurkovits Zita, Kozinszky Zoltan, Vari Sandor G, Guttman Andras
Horváth Csaba Memorial Laboratory of Bioseparation Sciences, Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Department of Obstetrics and Gynecology, University of Szeged, H-6725 Szeged, Hungary.
J Clin Med. 2025 Feb 27;14(5):1626. doi: 10.3390/jcm14051626.
Obesity is a rapidly growing common health problem worldwide that can lead to the development of gestational diabetes mellitus (GDM). However, GDM not only affects women with obesity but can also develop at any time, even after the OGTT test; therefore, an increasing number of complications related to GDM can be seen in both mothers and their children. It is necessary to discover biomarkers capable of indicating the development of GDM or complications during/after pregnancy. Since the N-glycosylation motif of human IgG has been described to change under many physiological and pathological conditions, it is a promising target for biomarker research. In our study, the effects of obesity and GDM were investigated on human serum IgG N-linked glycosylation patterns during human pregnancy. The study participants were categorized into four groups according to their body mass index (BMI) and GDM status: normal weight as control, obese (BMI > 30 kg/m), normal weight with GDM, and obese with GDM. The released N-glycan components of IgG were separated with capillary electrophoresis and detected using a laser-induced fluorescence detector. The result revealed several differences between the N-glycosylation patterns of the four study groups. Of this, 17 of the 20 identified structures differed significantly between the groups. The ratios of sialylated to non-sialylated structures were not changed significantly, but the core fucosylation level showed a significant decrease in the GDM and obese GDM groups compared to the control subjects. The lowest degree of core fucosylation was observed in the GDM group. The findings indicate that obesity in isolation does not have a significant impact on the IgG N-glycosylation pattern in pregnancy. Conversely, alterations in the N-glycan profile of antibodies may serve as biomarkers for the diagnosis of GDM in mothers with a normal BMI, although more evidence is needed. By incorporating glycan-based biomarkers into clinical practice, healthcare providers can improve early detection, personalize management strategies, and potentially mitigate adverse pregnancy outcomes associated with obesity and GDM.
肥胖是全球范围内迅速增长的常见健康问题,可导致妊娠期糖尿病(GDM)的发生。然而,GDM不仅影响肥胖女性,也可能在任何时候发生,甚至在口服葡萄糖耐量试验(OGTT)后;因此,在母亲及其子女中都能看到越来越多与GDM相关的并发症。有必要发现能够指示妊娠期GDM发生或其并发症的生物标志物。由于人类IgG的N-糖基化基序已被描述在许多生理和病理条件下会发生变化,因此它是生物标志物研究的一个有前景的靶点。在我们的研究中,调查了肥胖和GDM对人类孕期血清IgG N-连接糖基化模式的影响。研究参与者根据其体重指数(BMI)和GDM状态分为四组:正常体重作为对照组、肥胖(BMI>30 kg/m²)、患有GDM的正常体重者以及患有GDM的肥胖者。用毛细管电泳分离IgG释放的N-聚糖成分,并用激光诱导荧光检测器进行检测。结果显示四个研究组的N-糖基化模式存在若干差异。其中,20种已鉴定结构中的17种在各组之间有显著差异。唾液酸化与非唾液酸化结构之比没有显著变化,但与对照组相比,GDM组和肥胖GDM组的核心岩藻糖基化水平显著降低。在GDM组中观察到最低程度的核心岩藻糖基化。研究结果表明,单独的肥胖对孕期IgG N-糖基化模式没有显著影响。相反,抗体N-聚糖谱的改变可能作为诊断BMI正常母亲GDM的生物标志物,尽管还需要更多证据。通过将基于聚糖的生物标志物纳入临床实践,医疗保健提供者可以改善早期检测、个性化管理策略,并有可能减轻与肥胖和GDM相关的不良妊娠结局。