Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, Cork T12XF62, Ireland.
Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork T12DC4A, Ireland.
J Clin Endocrinol Metab. 2024 Apr 19;109(5):1275-1284. doi: 10.1210/clinem/dgad699.
Gestational diabetes mellitus (GDM) is a complex obstetric condition affecting localized glucose metabolism, resulting in systemic metabolic dysfunction.
This cross-sectional study aimed to explore visceral adipose tissue (VAT) as an integral contributor to GDM, focusing on elucidating the specific contribution of obesity and GDM pathology to maternal outcomes.
Fifty-six nulliparous pregnant women were recruited, including normal glucose tolerant (NGT) (n = 30) and GDM (n = 26) participants. Participants were subgrouped as nonobese (BMI <30 kg/m2) or obese (BMI ≥30 kg/m2). Metabolic markers in circulation, VAT, and placenta were determined. Morphological analysis of VAT and immunoblotting of the insulin signaling cascade were performed.
GDM participants demonstrated hyperinsulinemia and elevated homeostatic model assessment for insulin resistance (HOMA-IR) scores relative to NGT participants. The GDM-obese subgroup had significant VAT adipocyte hypoplasia relative to NGT-nonobese tissue. GDM-obese VAT had significantly lower insulin receptor substrate (IRS)-2 expression, with elevated ser312 phosphorylation of IRS-1, relative to NGT-nonobese. GDM-obese participants had significantly elevated circulating leptin levels and placental adipsin secretion, while GDM-nonobese participants had elevated circulating adipsin levels with reduced placental adiponectin secretion.
These findings suggest that GDM-obese pregnancy is specifically characterized by inadequate VAT remodeling and dysfunctional molecular signaling, which contribute to insulin resistance and hinder metabolic health.
妊娠糖尿病（GDM）是一种影响局部葡萄糖代谢的复杂产科疾病，导致全身代谢功能障碍。
本横断面研究旨在探讨内脏脂肪组织（VAT）作为 GDM 的一个组成部分，重点阐明肥胖和 GDM 病理对产妇结局的具体贡献。
招募了 56 名初产妇，包括正常糖耐量（NGT）（n=30）和 GDM（n=26）参与者。参与者分为非肥胖（BMI<30kg/m2）或肥胖（BMI≥30kg/m2）亚组。测定循环代谢标志物、VAT 和胎盘。进行 VAT 的形态学分析和胰岛素信号级联的免疫印迹。
与 NGT 参与者相比，GDM 参与者表现出高胰岛素血症和升高的稳态模型评估胰岛素抵抗（HOMA-IR）评分。与 NGT-非肥胖组织相比，GDM-肥胖亚组的 VAT 脂肪细胞明显萎缩。GDM-肥胖的 VAT 胰岛素受体底物（IRS）-2表达显著降低，IRS-1 的丝氨酸 312 磷酸化升高，而 NGT-非肥胖的则升高。GDM-肥胖参与者的循环瘦素水平和胎盘脂联素分泌显著升高，而 GDM-非肥胖参与者的循环脂联素水平升高，胎盘脂联素分泌减少。
这些发现表明，GDM 肥胖妊娠的特征是 VAT 重塑不足和功能障碍的分子信号，导致胰岛素抵抗并阻碍代谢健康。
