Institute for Experimental Endocrinology, Max Rubner Center for Cardiovascular Metabolic Renal Research, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Department of Endocrinology, Odense University Hospital, Kløvervænget, Odense C, and University of Southern Denmark, Odense, Denmark; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej, Odense C, Denmark.
Am J Clin Nutr. 2023 Dec;118(6):1224-1234. doi: 10.1016/j.ajcnut.2023.09.025. Epub 2023 Oct 7.
Diet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive.
The aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring.
This study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations.
Se and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006).
Low serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.
饮食是妊娠糖尿病（GDM）及其相关并发症的一个重要可改变的危险因素；然而，在硒（Se）等必需微量营养素方面的作用尚不确定，尤其是在硒摄入水平低的人群中。
本研究旨在探讨 3 种已确立的硒状态生物标志物与 GDM、妊娠期间血糖代谢和大于胎龄儿（LGA）后代之间的关系。
本研究纳入了来自丹麦奥登塞儿童队列前瞻性人群研究的 1346 名孕妇，共检测了 2294 份血清样本。在孕早期和孕晚期检测血清 Se、硒蛋白 P（SELENOP）浓度和谷胱甘肽过氧化物酶 3（GPX3）活性，在孕晚期检测空腹血糖和胰岛素水平。计算稳态模型评估的胰岛素抵抗指数（HOMA-IR），GDM 的定义根据世界卫生组织（WHO）2013 年空腹静脉血浆葡萄糖≥5.1mmol/L 的标准。亚组进行口服葡萄糖耐量试验。回归模型调整了各种混杂因素，量化了剂量依赖性关联。
Se 和 SELENOP 在妊娠期间下降。孕早期 GPX3 与孕晚期 GDM（WHO 2013 年标准）、空腹血糖、胰岛素、HOMA-IR 和 2 小时血糖呈剂量依赖性负相关。GPX3 活性每增加 1 个对数标度，GDM 的比值比（OR）为 0.33（95%CI：0.16，0.65）。孕晚期 GPX3 和 SELENOP 与 GDM 和 HOMA-IR 呈负相关；GPX3 和 SELENOP 每增加 1 个对数标度，GDM 的 OR 分别为 0.21（95%CI：0.12，0.38）和 0.52（95%CI：0.35，0.77）。妊娠期间 Se 生物标志物的下降与 GDM 和更高的 HOMA-IR 风险增加相关。孕晚期 GPX3 活性降低与 LGA 后代风险增加相关，部分（约 20%）通过空腹血糖浓度介导（P=0.006）。
妊娠期间血清 Se 水平较低，特别是 GPX3 活性，与 GDM 风险和大于胎龄儿有关。在妊娠期间进行 Se 状态评估可以识别出患有 GDM 风险较高的女性，她们可能受益于 Se 替代治疗。
