Association between hepatocyte growth factor/c-MET signaling and gestational diabetes (GDM) and GDM complications

Abstract

Background Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (c-MET) signaling is involved in glucose homeostasis in pancreatic β cells; however, studies on its relationship with gestational diabetes mellitus (GDM) are lacking. This study aimed to investigate HGF and its receptor, c-MET, in pregnant women with GDM and to analyze the correlation between HGF/c-MET signaling and GDM complications. Methods In total, 44 pregnant women with normal glucose tolerance (NGT) and 32 with GDM were studied. Serum levels of HGF and c-MET were measured using an enzyme-linked immunosorbent assay. The relative mRNA expression of HGF and c-MET was measured using real-time polymerase chain reaction. The protein expression of HGF and c-MET in placental and visceral fat tissues was measured using western blot analysis. Logistic regression and Pearson’s correlation analyses examined the associations of these variables with clinical information. Results Serum sc-MET levels were significantly higher (1472.58 vs. 1651.23 ng/mL, p < 0.001) and cord blood HGF levels were significantly lower (370.76 vs. 254.54 ng/mL, p = 0.042) in the GDM group than in the NGT group. The area under the receiver operating characteristic curve for sc-MET was 0.744 (95% confidence interval: 0.632–0.857, p < 0.001). The cut-off serum sc-MET level for predicting GDM was 1455.26 ng/mL. HGF protein expression in the maternal visceral fat tissue was significantly higher in the GDM group than in the NGT group (2-fold higher, p < 0.05). Serum HGF significantly correlated with cord arterial blood gas analysis (ABGA) base excess (r =-0.390, p = 0.007) and cord ABGA lactic acid (r = 0.469, p = 0.001). Cord blood HGF levels were significantly correlated with cord blood glucose levels (r = 0.439, p = 0.002). Conclusions We found an increase in serum sc-MET, a decrease in cord HGF, and an increase in HGF protein expression in the visceral fat tissue of the GDM group, indicating that HGF/c-MET signaling is related to GDM expression. In addition, maternal serum HGF levels correlated with base excess and lactic acid levels in cord ABGA, and cord blood HGF levels correlated with cord blood glucose levels. These outcomes suggest that HGF/c-MET signaling may have potential application in predicting GDM complications.