Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Quebec, Canada.
Diabetes Care. 2019 May;42(5):964-971. doi: 10.2337/dc18-2041. Epub 2019 Mar 4.
Fetal excessive exposure to glucocorticoids may program cardiometabolic risk. Placental 11 β-hydroxysteroid dehydrogenase 2 (11β-HSD2) serves as a barrier to prevent fetal overexposure to maternal glucocorticoids. It has not been explored whether placental 11β-HSD2 levels are associated with cardiometabolic health in postnatal life.
In a prospective birth cohort study of 246 mother-infant pairs, we measured placental 11β-HSD2 expression and maternal (32-35 weeks of gestation) and cord plasma cortisol concentrations. The primary outcomes were HOMA of insulin resistance (IR) and blood pressure (BP) in infants at age 1 year. Other outcomes included fasting insulin, HOMA β-cell function, carotid intima-media thickness, weight score, and skinfold thickness (triceps and subscapular) at age 1 year.
Placental 11β-HSD2 expression was negatively correlated with HOMA-IR ( = -0.17, = 0.021) and fasting insulin ( = -0.18, = 0.017) and marginally negatively correlated with systolic BP ( = -0.16, = 0.057) but was not correlated with HOMA of β-cell function, diastolic BP, carotid intima-media thickness, and skinfold thickness (all > 0.1) in infants at age 1 year. Cord plasma cortisol was negatively correlated to skinfold thickness ( = -0.20, = 0007) but was not correlated with other outcomes at age 1 year. Maternal plasma cortisol was positively correlated with maximal carotid intima-media thickness ( = 0.20, = 0.03) but was not correlated with other outcomes. Adjusting for maternal and infant characteristics, the associations were similar.
The study is the first to show that higher placental 11β-HSD2 expression is associated with lower IR in infancy. Independent cohort studies are required to confirm this novel finding.
胎儿过度暴露于糖皮质激素可能会增加心脏代谢风险。胎盘 11β-羟类固醇脱氢酶 2（11β-HSD2）作为一种屏障，可防止胎儿过度暴露于母体糖皮质激素。目前尚未探讨胎盘 11β-HSD2 水平是否与出生后生命的心脏代谢健康有关。
在一项对 246 对母婴进行的前瞻性出生队列研究中，我们测量了胎盘 11β-HSD2 的表达以及孕妇（妊娠 32-35 周）和脐带血浆皮质醇浓度。主要结局是婴儿 1 岁时的胰岛素抵抗（HOMA-IR）和血压（BP）。其他结局包括婴儿 1 岁时的空腹胰岛素、HOMA β 细胞功能、颈动脉内膜中层厚度、体重评分和皮褶厚度（三头肌和肩胛下）。
胎盘 11β-HSD2 的表达与 HOMA-IR（ = -0.17， = 0.021）和空腹胰岛素（ = -0.18， = 0.017）呈负相关，与收缩压（ = -0.16， = 0.057）呈负相关，但与 HOMA β 细胞功能、舒张压、颈动脉内膜中层厚度和皮褶厚度（均 > 0.1）无关。脐带血浆皮质醇与皮褶厚度呈负相关（ = -0.20， = 0.0007），但与婴儿 1 岁时的其他结果无关。母体血浆皮质醇与最大颈动脉内膜中层厚度呈正相关（ = 0.20， = 0.03），但与其他结果无关。调整了母亲和婴儿的特征后，结果相似。
这项研究首次表明，较高的胎盘 11β-HSD2 表达与婴儿期胰岛素抵抗降低有关。需要独立的队列研究来证实这一新发现。
