First trimester secreted Frizzled-Related Protein 4 and other adipokine serum concentrations in women developing gestational diabetes mellitus

Abstract

Background 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). Methods 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). Results 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). Conclusion 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.

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

“…Of the 9 cord blood proteins associated with birth weight and body anthropometrics in this study, 3 are associated with metabolism or metabolic disorders. High serum whole blood afamin and SFRP4 concentrations in the first trimester have been associated with the onset of gestational diabetes . Both afamin overexpression in transgenic mice and gestational diabetes in humans have been associated with a higher birth weight and/or increased risk of large for gestational age, which is in line with the findings of this study.…”

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

“…PCSK9 [79], APCDD1 [80], SFRP4 [81], MFAP5 [82] and PKP2 [83] are associated to the risk of obesity. Studies show that PCSK9 [84] and SFRP4 [85] are involved in the process of gestational diabetes mellitus. The PCSK9 [86], SEMA3A [87], SFRP4 [81] and BMP6 [88] were found as potential biomarkers for diabetes mellitus.…”

Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes—A Scoping Review

“…Secreted frizzled-related protein 4 (sFRP4) has been shown to play a role in glucose metabolism, reflecting islet inflammation and impaired insulin secretion [ 325 ]. Schuitemaker et al [ 326 ] found significantly higher first-trimester levels of sFRP4 in women, who subsequently developed GDM (n = 50, diagnostic criteria fasting glucose ≥ 7.0 mmol/L, 2 h glucose ≥ 7.8 mmol/L) compared to controls and a predictive capacity expressed as AUC of 0.60 (95% CI 0.50–0.70). The correlation between sFRP4 and GDM is supported by other studies [ 327 , 328 ]…”