Dey Bishal Kumar, Banerjee Sudipta, Adhikary Pieu, Chowdhury Subhankar, Roy Sanchita, Roy Subesha Basu, Bhattacharjee Rana
Department of Endocrinology & Metabolism, IPGME&R and SSKM Hospital, 244, A.J.C. Bose Road, Kolkata, West Bengal, 700020, India.
Department of Anatomy, Diamond Harbour Govt. Medical College & Hospital, Diamond Harbour, West Bengal, 743331, India.
Acta Diabetol. 2025 Sep 10. doi: 10.1007/s00592-025-02581-5.
Gestational diabetes mellitus (GDM) is defined as glucose intolerance first identified during pregnancy that does not meet the criteria for overt diabetes. Its pathophysiology shares key features with type 2 diabetes mellitus (T2D), including insulin resistance and inflammation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are implicated in T2D. This study investigates the gene expression of lncRNAs in GDM and explores their association with insulin resistance and proinflammatory cytokines.
This cross-sectional study included 25 GDM and 36 non-GDM (NGDM) participants from a tertiary care antenatal clinic. GDM was diagnosed using a 75 g oral glucose tolerance test (OGTT) based on the International Association of Diabetes and Pregnancy Study Groups criteria. MALAT1, MEG3, and XIST were selected for analysis due to their reported involvement in T2D. Their gene expression levels were quantified using real-time PCR, while serum concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and glycemic markers (C-peptide, fasting insulin) were measured using ELISA.
MALAT1, MEG3, and XIST were significantly downregulated in the GDM group compared to the NGDM group (p < 0.01). In the GDM group, all three lncRNAs showed a significant negative correlation with Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) (MALAT1: r = -0.44, p = 0.03; MEG3: r = -0.46, p = 0.04; XIST: r = -0.45, p = 0.04). Additionally, MALAT1 gene expression negatively correlated with IL-6 (r = -0.49, p = 0.03) and TNF-α (r = -0.48, p = 0.04). MEG3 and XIST gene expression negatively correlated with IL-1β (r = -0.51 and - 0.50, p = 0.03 for both) and TNF-α (r = -0.47 and - 0.52, p = 0.04 and 0.03, respectively).
MALAT1, MEG3, and XIST are downregulated in GDM, and their gene expression levels are negatively correlated with insulin resistance and select proinflammatory cytokines. These findings suggest a potential role for lncRNA downregulation in GDM pathogenesis, warranting further investigation.
妊娠期糖尿病（GDM）被定义为首次在孕期发现的葡萄糖不耐受，且不符合显性糖尿病的标准。其病理生理学与2型糖尿病（T2D）具有关键特征，包括胰岛素抵抗和炎症。新出现的证据表明，长链非编码RNA（lncRNA）与T2D有关。本研究调查了GDM中lncRNA的基因表达，并探讨它们与胰岛素抵抗和促炎细胞因子的关联。
这项横断面研究纳入了来自一家三级医疗产前诊所的25名GDM患者和36名非GDM（NGDM）参与者。根据国际糖尿病与妊娠研究组的标准，采用75克口服葡萄糖耐量试验（OGTT）诊断GDM。由于已报道MALAT1、MEG3和XIST与T2D有关，因此选择它们进行分析。使用实时PCR对它们的基因表达水平进行定量，同时使用酶联免疫吸附测定法（ELISA）测量促炎细胞因子（TNF-α、IL-6、IL-1β）和血糖标志物（C肽、空腹胰岛素）的血清浓度。
与NGDM组相比，GDM组中MALAT1、MEG3和XIST显著下调（p < 0.01）。在GDM组中，所有三种lncRNA均与胰岛素抵抗稳态模型评估（HOMA-IR）呈显著负相关（MALAT1：r = -0.44，p = 0.03；MEG3：r = -0.46，p = 0.04；XIST：r = -0.45，p = 0.04）。此外，MALAT1基因表达与IL-6（r = -0.49，p = 0.03）和TNF-α（r = -0.48，p = 0.04）呈负相关。MEG3和XIST基因表达与IL-1β（r分别为 -0.51和 -0.50，p均为0.03）以及TNF-α（r分别为 -0.47和 -0.52，p分别为0.04和0.03）呈负相关。
GDM中MALAT1、MEG3和XIST下调，且它们的基因表达水平与胰岛素抵抗和某些促炎细胞因子呈负相关。这些发现表明lncRNA下调在GDM发病机制中可能起作用，值得进一步研究。
