Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, Cork, Ireland.
Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland.
Clin Exp Immunol. 2024 May 16;216(3):280-292. doi: 10.1093/cei/uxae010.
Gestational diabetes mellitus (GDM) is a frequent and serious complication of pregnancy, often associated with obesity. Metabolic dysfunction and metainflammation are evident in both obesity and GDM. In this cross-sectional study, we aimed at defining the direct contribution of the immune system in GDM, across the main metabolic tissues, specifically focussing on elucidating the roles of obesity and GDM to the clinical outcome. Using immunoassays and multicolour flow cytometry, cytokine profiles and immune cell frequencies were measured in maternal circulation and central metabolic tissues [placenta and visceral adipose tissue (VAT)] in GDM-diagnosed (n = 28) and normal glucose tolerant (n = 32) women undergoing caesarean section. Participants were sub-grouped as non-obese [body mass index (BMI) < 30 kg/m2] or obese (BMI ≥ 30 kg/m2). Unsupervised data analysis was performed on the flow cytometry data set to identify functional alterations. GDM obese participants had significantly elevated circulating IL-6 and IL-17A levels. GDM non-obese participants had elevated circulating IL-12p70, elevated placental IL-17A, and VAT IFN-γ production. Unsupervised clustering of immune populations across the three biological sites simultaneously, identified different NK- and T-cell phenotypes that were altered in NGT obese and GDM non-obese participants, while a classical tissue monocyte cluster was increased in GDM obese participants. In this study, there was significant evidence of subclinical inflammation, and significant alterations in clusters of NK cells, T cells, and tissue monocyte populations in GDM. While increased adiposity assimilates with increased inflammation in the non-pregnant state, this overt relationship may not be as evident during pregnancy and warrants further examination in future longitudinal studies.
妊娠期糖尿病（GDM）是一种常见且严重的妊娠并发症，常与肥胖有关。代谢功能障碍和代谢性炎症在肥胖和 GDM 中都很明显。在这项横断面研究中，我们旨在确定免疫系统在 GDM 中的直接作用，跨越主要代谢组织，特别关注阐明肥胖和 GDM 对临床结果的作用。使用免疫测定和多色流式细胞术，在 GDM 诊断（n=28）和正常葡萄糖耐量（n=32）的妇女剖宫产时测量母血循环和中央代谢组织（胎盘和内脏脂肪组织[VAT]）中的细胞因子谱和免疫细胞频率。参与者被分为非肥胖组（BMI<30kg/m2）或肥胖组（BMI≥30kg/m2）。对流式细胞术数据集进行无监督数据分析，以确定功能改变。GDM 肥胖组参与者的循环 IL-6 和 IL-17A 水平显著升高。GDM 非肥胖组参与者的循环 IL-12p70 升高，胎盘 IL-17A 升高，VAT IFN-γ 产生增加。对三个生物部位的免疫群体进行无监督聚类，同时鉴定了在 NGT 肥胖和 GDM 非肥胖组中改变的不同 NK 和 T 细胞表型，而在 GDM 肥胖组中增加了经典组织单核细胞群。在这项研究中，有明显的证据表明存在亚临床炎症，以及 NK 细胞、T 细胞和组织单核细胞群的聚类有明显改变。虽然在非妊娠状态下，增加的肥胖与增加的炎症有关，但这种明显的关系在妊娠期间可能不那么明显，需要在未来的纵向研究中进一步研究。
