Endocrine Abstracts

Background: Placental signalling has been postulated to drive inflammation, endothelial dysfunction and insulin resistance in gestational diabetes mellitus (GDM).

Objectives: To determine if placental signalling contributes to systemic insulin resistance in GDM.

Methods: Adiponectin, leptin, adipsin and resistin in placental and omental explant culture supernatants (n=10 GDM and n=10 control) and maternal plasma (n=20 GDM and n=20 control) were quantified using LEGENDplex ELISA. Insulin levels were quantified in maternal plasma (n=20 GDM and n=20 control) using ELISA (R&D/Bio-Techne). Insulin signalling pathway proteins were quantified in GDM (n=8) and control (n=8) omental tissue lysates by western blotting. Histological staining was used to characterise adipocyte structure and omental tissue fibrosis (picro-sirius red) in GDM (n=15) and control (n=15) participants.

Results: Circulating plasma levels of adiponectin are significantly lower in GDM participants vs control (37.85µg/ml ± 20.22µg/ml vs. 49.7µg/ml ± 10.85µg/ml, P = 0.033). No significant differences were observed in adipokine release from omentum explant cultures. GDM placental explants had lower leptin release (0.29ng/ml ± 0.21ng/ml vs. 0.81ng/ml ± 0.65ng/ml, P = 0.046) and higher adipsin release (37.76ng/ml ± 9.25ng/ml vs. 29.43ng/ml ± 5.31ng/ml, P = 0.028) relative to control. Insulin levels were significantly higher in GDM participants (135.3pmol/l ± 151.5pmol/l vs. 39.24pmol/l ± 14.36pmol/l, P = 0.006). There was significantly higher expression of phosphorylated IRS1 (Ser307)/IRS1 (P = 0.039) in GDM omentum relative to healthy controls. GDM omentum samples had a significantly lower ratio of IRS2/IRS1 relative to healthy control samples (P = 0.039). Histological analysis showed that GDM omental tissue has a significantly lower adipocyte count relative to healthy pregnancies (147.8 ± 41.6 vs. 173.1 ± 45.2, P = 0.038), independent of participant BMI, with no change in adipocyte size or fibrosis.

Conclusions: In GDM pregnancies, visceral adipose tissue lacks the protective adipocyte hyperplasia, which helps to maintain glycaemic homeostasis. Reduced circulating adiponectin and altered placental adipokine release may drive adipocyte dysfunction and insulin resistance in GDM.