Secreted frizzled-related protein 3 is associated with metabolic disturbances in gestational diabetes

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.

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.

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.

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.