Department of Reproductive and Perinatal Health Research, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico.
Obstetric and Gynecology Department, Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico.
Int J Mol Sci. 2024 Oct 30;25(21):11641. doi: 10.3390/ijms252111641.
Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD's cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD's impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD's complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.
妊娠期糖尿病（GD）是一种代谢紊乱，表现为妊娠期间葡萄糖耐量受损，对母婴健康有重大影响。其全球患病率约为 14%，危险因素包括肥胖、糖尿病家族史、高龄和种族，这些因素与葡萄糖调节和胰岛素抵抗的细胞和分子紊乱有关。GD 与母亲和新生儿的短期和长期并发症有关。对于母亲，GD 会增加其患 2 型糖尿病、心血管疾病和代谢综合征的风险。对于后代，宫内 GD 暴露使他们在以后的生活中易患肥胖、葡萄糖耐量受损和代谢紊乱。本综述旨在阐明 GD 背后复杂的细胞和分子机制，为开发有效的治疗策略提供信息。使用与 GD 的细胞和分子病理生理学相关的医学主题词（MeSH）术语进行了系统综述。纳入标准包括关注 GD 对母婴健康影响的原始研究、系统综述和荟萃分析，符合 PRISMA 指南。数据提取包括研究特征、母婴结局、主要发现和结论。GD 破坏胰岛素信号通路，导致葡萄糖摄取受损和胰岛素抵抗。线粒体功能障碍会降低 ATP 产生并增加活性氧，从而加剧氧化应激。激素影响、慢性炎症和哺乳动物雷帕霉素靶蛋白（mTOR）通路的失调进一步损害胰岛素信号。肠道微生物群的改变、基因表达和表观遗传修饰在 GD 中起着重要作用。铁死亡和胎盘功能障碍主要导致宫内生长受限。相反，胎儿巨大症是由母体高血糖和随后的胎儿高胰岛素血症引起的，导致胎儿过度生长。与 GD 相关的慢性炎症状态和氧化应激加剧了这些并发症，形成了一个恶劣的宫内环境。GD 的复杂病理生理学涉及胰岛素信号、线粒体功能、炎症和氧化应激的多个中断。有效的管理需要早期发现、预防策略和国际合作，以标准化护理并改善母婴的结局。
