Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Department of Pediatrics, University of South Dakota, Sioux Falls, SD, United States.
Front Endocrinol (Lausanne). 2022 Feb 7;13:836541. doi: 10.3389/fendo.2022.836541. eCollection 2022.
Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.
妊娠期糖尿病与母体胰岛素、瘦素和白细胞介素-6（IL-6）水平升高有关。在胎盘内，IL-6 可进一步刺激瘦素产生。尽管瘦素和 IL-6 在结构上具有相似性且在炎症中具有共同作用，但它们对神经发育的影响却截然相反，而且母体糖尿病或绒毛膜羊膜炎对胎儿激素暴露的相对重要性尚未确定。我们假设，在伴有母体糖尿病和绒毛膜羊膜炎的妊娠中，IL-6 和瘦素之间会存在正相关关系，且随着疾病严重程度的增加，激素水平也会逐渐升高。为了验证这一假设，我们从 104 例足月分娩的婴儿中获取脐血样本，其中 47 例婴儿的母亲患有糖尿病。采用多重分析方法测定瘦素、胰岛素和白细胞介素-6 的水平。采用单变量和多变量线性回归分析确定与激素水平独立相关的因素。与 IL-6 不同，瘦素和胰岛素水平随母体糖尿病而显著升高。母体 BMI 和出生体重是瘦素和胰岛素的独立预测因子，且出生体重是预测瘦素的最强因素。临床诊断的绒毛膜羊膜炎和新生儿败血症与 IL-6 增加有关，但与瘦素无关。在没有败血症的适于胎龄儿中，IL-6 和瘦素呈强相关（R=0.6，P<0.001）。总之，母体糖尿病和出生体重与瘦素有关，而绒毛膜羊膜炎与白细胞介素-6 有关。在存在增加的脐血白细胞介素-6 水平的情况下，瘦素和白细胞介素-6 之间呈正相关关系仅限于没有败血症的婴儿，这表明足月婴儿和胎盘可能具有有限的能力增加脐血中神经保护激素瘦素的水平。
