Secreted Frizzled-Related Proteins 4 and 5: What They Are and Can They Be Used as a Biomarker in Gestational Diabetes Mellitus

During pregnancy the maternal metabolic profile changes from an anabolic to a catabolic state, however some women are unable to sufficiently adapt their metabolic profile and develop a de novo hyperglycemic state, called gestational diabetes mellitus (GDM). Since the risk of adverse pregnancy outcomes related to GDM are already present during the diagnosis of GDM, there is a search for a method to earlier predict its development in order to start a (therapeutic) intervention. Secreted frizzled-related protein 4 (sFRP4) and secreted frizzled-related protein 5 (sFRP5) are two antagonistic proteins for the Wingless and Int-1 (Wnt) signaling pathway and both are possibly involved in the development of diabetes. In addition, they are associated with the development of the placenta and differential expression of both proteins is observed in various pregnancy-related disorders. Therefore, this chapter describes the glucose homeostasis during pregnancy, the definition of GDM, and evaluate the role of sFRP4 and sFRP5 in the development of diabetes and their (potential) association with the development of GDM.