Endocrine Abstracts

Background: Gestational diabetes mellitus (GDM) is associated with increased rates of large-for-gestational-age (LGA) or small-for-gestational-age (SGA) infants. Currently, it is not possible to predict which women with GDM are at risk of delivering LGA or SGA infants. Fetuin-A, (α 2-Heremans Schmid glycoprotein; AHSG), a glycoprotein associated with insulin resistance is altered in GDM maternal serum. It is unclear if levels are related to altered fetal growth. This study aimed to establish whether maternal serum fetuin-A has the potential to predict pathological fetal growth in pregnancies complicated by GDM.

Methods: Serum was collected from women with and without GDM between 26-32 weeks’ gestation. Women were tracked to delivery, and fetal sex and birthweight centiles recorded. Serum extracellular vesicles (EVs) were isolated by size exclusion chromatography (SEC) and characterised by electron microscopy (shape), nanoparticle tracking analysis (NTA; size/concentration) and Western blotting (EV-enriched proteins). Levels of fetuin A in total serum, EV-enriched and EV-depleted fractions were assessed by Western blotting and ELISA.

Results: EVs were detected in early SEC fractions but absent from later fractions. Fetuin-A was not detected in EVs but was present in total serum and in EV-depleted fractions. Women with GDM (n = 23) had significantly lower levels of fetuin-A compared to non-GDM pregnancies (n = 25; P = 0 .0089). Fetuin-A was not changed in women with GDM that delivered LGA babies (n = 7) but was significantly increased in women that delivered SGA compared to appropriate-for-gestational-age (AGA) infants, in both GDM (n = 4; P < 0.0232) and non-GDM patients (n = 6; P = 0 .0097).

Conclusions: Fetuin-A is present in maternal serum but is not contained in EVs. Levels of serum fetuin-A are reduced in pregnancies complicated by GDM compared to uncomplicated pregnancies. Increased fetuin-A in SGA pregnancies, suggests that maternal fetuin-A levels may be important for predicting which pregnancies are at risk of delivering SGA infants, irrespective of GDM status.