Sarıkaya Sevcan, Almaghrebi Eissa, Akat Fatma, Hepbildi Eda Nur, Kosucu Esra, Körez Muslu Kazım, Vatansev Husamettin
Department of Obstetrics and Gynecology, Health Sciences University, Konya City Hospital, Konya, Türkiye.
Department of Medical Biochemistry, Selcuk University Faculty of Medicine, Konya, Türkiye.
Int J Gynaecol Obstet. 2025 Aug;170(2):774-782. doi: 10.1002/ijgo.70091. Epub 2025 Mar 27.
Our aim in this study was to evaluate the levels of Activating Transcription Factor-6 (ATF-6), Inositol-Requiring Enzyme 1 (IRE-1), and C/EBP-Homologous Protein (CHOP), which are critical markers of endoplasmic reticulum (ER) stress, in patients with gestational diabetes mellitus (GDM), a condition increasingly recognized for its complex biochemical and molecular underpinnings.
A total of 89 patients aged 18-45 years who applied to our hospital between January 2024 and December 2024 were included in our study. Of these, 45 patients were diagnosed with GDM during their routine pregnancy follow-up, while 44 were healthy pregnant women without any additional metabolic or obstetric complications. Serum samples were analyzed for ATF6, IRE-1, and CHOP levels, which are biochemical markers associated with ER stress. The data obtained were compared between the two groups.
The patients with GDM were older than those in the control group (31.98 ± 5.29 vs. 27.55 ± 5.92 years, P < 0.001). The mean number of gravidas (3.96 ± 2.01 vs. 2.48 ± 1.62, P < 0.001) and parity (2.18 ± 1.45 vs. 1.14 ± 1.07, P < 0.001) were significantly higher in the GDM group than in the control group. All GDM patients showed elevated levels of hemoglobin A1c (HbA1C) (6.69 ± 1.43% or 49.24 ± 15.25 mmol/mol, n = 45), indicating chronic hyperglycemia. GDM patients had elevated levels of red blood cells (RBC), hematocrit (HCT), mean platelet volume (MPV), platelet distribution width (PDW), red cell distribution width-coefficient of variation (RDW-CV) and potassium. They also had decreased glucose levels. Analysis revealed that there was no significant change in CHOP and IRE-1 levels in the GDM women compared with patients in the control group. However, the level of ATF-6 was significantly reduced in the GDM group compared with the control group (5.30, interquartile range [IQR] 4.59-6.28 vs. 5.92, IQR 5.17-8.43; P = 0.040). Despite no significant changes in CHOP and IRE-1 levels, the reduced ATF-6 levels in GDM patients highlight its potential as a specific biomarker for ER stress in the context of GDM.
This study identifies ATF-6 as a potential biomarker for GDM, with reduced levels significantly associated with GDM and key clinical parameters. Our findings support the integration of ER stress and hematological markers into future research and clinical practice for GDM.
本研究旨在评估活化转录因子6（ATF - 6）、肌醇需求酶1（IRE - 1）和C/EBP同源蛋白（CHOP）的水平，这些是内质网（ER）应激的关键标志物，在妊娠期糖尿病（GDM）患者中进行评估，GDM这种病症因其复杂的生化和分子基础而日益受到认可。
2024年1月至2024年12月期间到我院就诊的89例年龄在18 - 45岁的患者纳入本研究。其中，45例患者在常规孕期随访中被诊断为GDM，而44例为无任何额外代谢或产科并发症的健康孕妇。分析血清样本中与ER应激相关的生化标志物ATF6、IRE - 1和CHOP的水平。将两组获得的数据进行比较。
GDM患者比对照组患者年龄更大（31.98±5.29岁 vs. 27.55±5.92岁，P < 0.001）。GDM组的平均妊娠次数（3.96±2.01 vs. 2.48±1.62，P < 0.001）和产次（2.18±1.45 vs. 1.14±1.07，P < 0.001）显著高于对照组。所有GDM患者糖化血红蛋白（HbA1C）水平升高（6.69±1.43%或49.24±15.25 mmol/mol，n = 45），表明存在慢性高血糖。GDM患者的红细胞（RBC）、血细胞比容（HCT）、平均血小板体积（MPV）、血小板分布宽度（PDW）、红细胞分布宽度变异系数（RDW - CV）和钾水平升高。他们的血糖水平降低。分析显示，与对照组患者相比，GDM女性的CHOP和IRE - 1水平无显著变化。然而，与对照组相比，GDM组的ATF - 6水平显著降低（5.30，四分位数间距[IQR] 4.59 - 6.28 vs. 5.92，IQR 5.17 - 8.43；P = 0.040）。尽管CHOP和IRE - 1水平无显著变化，但GDM患者中ATF - 6水平降低凸显了其作为GDM背景下ER应激特异性生物标志物的潜力。
本研究确定ATF - 6为GDM的潜在生物标志物，其水平降低与GDM及关键临床参数显著相关。我们的研究结果支持将ER应激和血液学标志物纳入未来GDM的研究和临床实践中。
