Varthaliti Antonia, Lygizos Vasilios, Fanaki Maria, Pergialiotis Vasilios, Papapanagiotou Angeliki, Pappa Kalliopi, Theodora Marianna, Daskalaki Maria Anastasia, Antsaklis Panos, Daskalakis George
1st Department of Obstetrics and Gynecology, "Alexandra" General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece.
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece.
Biomedicines. 2025 Jul 2;13(7):1627. doi: 10.3390/biomedicines13071627.
Gestational diabetes mellitus (GDM) occurs in approximately 9-25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications.
妊娠期糖尿病（GDM）约发生于9%-25%的妊娠中，若未被诊断或控制不当，无论短期还是长期，都可能对母亲和胎儿产生不良后果。GDM的特征是孕期出现或首次被识别的葡萄糖不耐受，是一种多因素疾病，其病理生理学仍未完全明确。它与慢性低度炎症状态密切相关，这种炎症状态会导致胰岛素抵抗，而胰岛素抵抗是GDM发病机制的一个标志。在这一过程中涉及的基本促炎细胞因子中，TNF-α和IL-6起核心作用。TNF-α是一种主要由活化巨噬细胞分泌的细胞因子，在肥胖情况下脂肪细胞也会分泌。许多研究表明，与血糖正常的孕妇相比，GDM孕妇体内其水平升高。IL-6是另一种由免疫细胞、脂肪组织和胎盘分泌的促炎细胞因子。在并发GDM的妊娠期间，母体循环中其浓度更高。TNF-α和IL-6协同作用，使子宫内促炎环境持续存在。它们的联合作用会加剧胰岛素抵抗，并可能损害孕期胰腺β细胞的代偿功能，从而促使遗传或代谢易感个体发生GDM。最近的研究发现了各种母体血清生物标志物，如TNF-α和IL-6，它们可能有望用于GDM的早期检测。我们研究的目的是评估TNF-α和IL-6是否可作为GDM早期诊断的诊断工具，以便及时干预并降低相关母婴并发症的风险。
