IGFs and IGF-Binding Proteins in Pregnancy and Gestational Diabetes Mellitus

Abstract

The insulin-like growth factor (IGF) axis is involved in the regulation of growth and metabolism; however, little is known about its role in the development of gestational diabetes mellitus (GDM). The aim of our study was to determine serum IGF-1, IGF-2 and selected IGF binding protein (IGFBP) levels and their mRNA expression in subcutaneous (SAT) and visceral adipose tissue (VAT) and placenta in the context of pregnancy and GDM. Thirty-seven pregnant females - 21 with GDM (GDM group) and 16 without GDM (P group) - and 15 age-matched non-pregnant control females (NP group) were included into the study. Blood samples were taken in 28th-32th and 36th-38th gestational week and 6-12 months after delivery (GDM and P group) or before diagnostic laparoscopy (NP group). SAT, VAT and placental samples were obtained during delivery or surgery, respectively. Compared with NP group serum IGF-1, IGFBP-1 and 3 were increased in both GDM and P subjects reaching maximum levels in 38th-39th gestational week. IGF-2 was elevated only in GDM group culminating 6 months after delivery (745.1±24.7 vs. 909.2±62.8 vs. 998.7±92.7 ng/ml, p=0.017 for GDM and 726.9±28.4 vs. 791.2±44.2 vs. 748.9±58.4 ng/ml, p=0.341 for P group, respectively). IGFBP-3 was higher and IGFBP-4 was decreased in GDM vs. P group during the whole study (IGFBP3: 631.0±22.9 vs. 536.9±15.4 ng/ml, p=0.003 for GDM vs. P group; IGFBP4: 14.79±2.71 vs. 22.78±2.94 ng/ml, p<0.001 for GDM vs. P group). mRNA expression of IGF-1, IGFBP-3, 4 and 5 was increased in SAT, while IGF-2 and IGFBP-4 mRNA was elevated in VAT in GDM and P relative to NP group. Placental mRNA expression of IGF-2, IGF-2 receptor, IGFBP-3 and 4 was higher in GDM compared with P group. In conclusion, females with GDM had increased serum IGF-2, IGFBP-3 and reduced IGFBP-4 levels and elevated placental mRNA expression of several components of IGF axis compared with pregnant women without GDM. These changes might play a role in the development of GDM. Disclosure K. Anderlová: None. P. Simjak: None. A. Cinkajzlova: None. J. Klouckova: None. H. Kratochvilova: None. Z. Lacinová: None. P. Kaválková: None. H. Krejci: None. M. Mraz: None. M. Haluzik: None. M. Krsek: None.