Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Research & Development, IQ Products BV, Groningen, The Netherlands.
PLoS One. 2020 Nov 18;15(11):e0242423. doi: 10.1371/journal.pone.0242423. eCollection 2020.
The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM).
In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC).
First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793).
In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.
本研究旨在评估妊娠早期可溶性卷曲相关蛋白 4（sFRP4）浓度是否单独或与瘦素、Chemerin 和/或脂联素联合与妊娠期糖尿病（GDM）的发生有关。
在巢式病例对照研究中，50 名自然受孕并分娩活产婴儿的 GDM 患者与总共 100 名无并发症的单胎对照妊娠根据体重指数（±2kg/m2）、采样时的孕龄（确切日期）和母亲年龄（±2 岁）进行匹配。在妊娠 70-90 天期间获得血清样本，通过 ELISA 测定 sFRP4、Chemerin、瘦素和脂联素的浓度。在对数转换浓度后，使用单变量和多变量逻辑回归分析进行统计比较。通过曲线下面积（AUC）评估模型的区分能力。
GDM 病例的妊娠早期 sFRP4 浓度显著升高（2.04 与 1.93ng/ml；p<0.05），Chemerin（3.19 与 3.15ng/ml；p<0.05）和瘦素（1.44 与 1.32ng/ml；p<0.01）也是如此。GDM 病例的脂联素浓度显著降低（2.83 与 2.94ng/ml；p<0.01）。进一步分析仅显示 sFRP4 与 Chemerin（R2=0.124；p<0.001）和瘦素（R2=0.145；p<0.001）以及 Chemerin 与瘦素（R2=0.282；p<0.001）之间存在微弱但显著的相关性仅在对照组中。在这四个标志物的多元逻辑回归模型中，只有脂联素与 GDM 显著相关（比值比 0.12，95%CI 0.02-0.68）。该模型的 AUC 为 0.699（95%CI 0.605-0.793）。
在妊娠早期，sFRP4、瘦素、Chemerin 和脂联素的多标志物模型与 GDM 的发生有关。因此，该标志物组合似乎是一个很有前途的候选标志物，可以在进一步的前瞻性研究中评估其对 GDM 的预测价值。
