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Wnt/β Catenin Signaling in Development and Cancer · Journal article
Frontiers in Endocrinology · August 14, 2026
Encouraging direction, but not yet definitive.
This longitudinal cohort study measured plasma Wnt modulators (DKK1 and sFRP3) in 284 pregnant women and found that lower sFRP3 early in pregnancy correlates with markers of obesity, inflammation, insulin resistance, and dyslipidaemia in GDM, while persistently low DKK1 associated with increased aortic stiffness at 5-year follow-up. The findings are observational and establish associations rather than causation or clinical utility; replication and mechanistic validation are needed.
Longitudinal cohort study. 284 women enrolled during pregnancy and followed to 5 years postpartum; no specific setting, eligibility criteria, or stratification by GDM status stated in the abstract.. Compared with: Women with GDM compared to those without GDM (implied by study aims and results sections).. n = 284.
Plasma DKK1 was lower throughout pregnancy in women with GDM sFRP3 was lower early in pregnancy in women with GDM and correlated with obesity indices, adipose tissue inflammation, insulin resistance, poor β-cell function, and unfavorable lipid ratios Low DKK1 during pregnancy was associated with higher aortic stiffness at 5-year follow-up
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These findings suggest sFRP3 and DKK1 may serve as biomarkers for metabolic dysregulation and future cardiovascular risk in GDM, but the observational design does not establish clinical utility or inform treatment decisions. Further mechanistic studies and validation in independent cohorts are required before clinical application.
A longitudinal cohort study with repeated biomarker measurements linking circulating Wnt modulators to metabolic dysregulation in GDM, but based on observational associations rather than intervention or definitive clinical outcomes.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest sFRP3 and DKK1 may serve as biomarkers for metabolic dysregulation and future cardiovascular risk in GDM, but the observational design does not establish clinical utility or inform treatment decisions. Further mechanistic studies and validation in independent cohorts are required before clinical application.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Aims Secreted modulators of the Wingless (WNT) pathways are associated with cardiometabolic dysregulation. Among these, Dickkopf-1 (DKK1) and secreted frizzled-related protein-3 (sFRP3) are abundantly expressed in placental tissue and secreted into the maternal circulation. We hypothesized their plasma levels would be dysregulated in women with gestational diabetes mellitus (GDM) and correlate with indices of metabolic health. Methods A total of 284 women during pregnancy and at 5 years postpartum participated in this longitudinal cohort study. Secreted Wnt modulators were analyzed by enzyme immunoassay 4 times during pregnancy and postpartum. Lipids and indices of glucose tolerance were assessed twice in pregnancy and at follow-up. Body composition and pulse wave velocity analysis was assessed at follow-up. Results Our main findings: i) plasma DKK1 was lower throughout pregnancy in women with GDM. ii) sFRP3 was lower early in pregnancy in women with GDM and correlated with indices of obesity and adipose tissue related inflammation, insulin resistance, poor β-cell function and unfavorable lipid ratios. iii) low DKK1 during pregnancy was associated with higher aortic stiffness at follow-up. Conclusions Low plasma sFRP3 during early pregnancy is associated with metabolic and inflammatory dysregulation while persistently low DKK1 may be associated with future cardiovascular disease risk in GDM pregnancies.
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