Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

Abstract

Objective: Human fetuin/a 2 -HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. Design: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. Methods: Serum AHSG was determined by radial immunodiffusion. Results: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-a (TNF-a), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-a, leptin levels and head circumference, body length and body weight of newborns. Conclusion: AHSG, TNF-a and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

Preeclampsia is associated with decreased serum α2-HS glycoprotein (fetuin-A) concentration

“…We have found earlier that AHSG along with tumor necrosis factor-a and leptin may negatively regulate neonatal skeletal development. 35 In a recent study, no significant differences were observed in maternal, fetal and neonatal AHSG concentrations between pregnancies with normal and asymmetrically restricted fetal growth, 34 which is consistent with our findings. Beyond its concentration, the post-translational modifications of the protein (phosphorylation and glycosylation) can also influence the biological activity of AHSG.…”

“…33,34 Our research group has previously reported that serum AHSG concentration increases with advancing gestation in normal pregnancy. 35 According to our findings, the maternal systemic inflammatory response, which involves an acute-phase reaction, accounts-at least partly-for the decreased serum AHSG levels in preeclampsia, as suggested by the significant inverse correlation with serum CRP concentrations. In fact, circulating AHSG levels decrease in several conditions characterized by tissue damage, infection, inflammation or malignancy.…”

“…2 According to our previous findings, AHSG may contribute to insulin resistance during normal pregnancy and gestational diabetes. 35 In spite of its strength due to the large number of preeclamptic patients and healthy pregnant women involved, our study is limited by its case-control design. A prospective study should be undertaken to determine whether a decrease in the serum AHSG concentration precedes the development of preeclampsia, and thus can help predict this serious complication in pregnancy.…”

Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

“…This is an important indicator that AHSG is involved in the insulin signaling pathway. Furthermore, it appears to boost the likelihood of developing gestational diabetes during pregnancy (Srinivas et al, 1993;Kalabay et al, 2002;Swallow et al, 2004;Stefan et al, 2006;Briana et al, 2008). In fact, our results show that serum AHSG levels were increased in the PE group as determined by both the SRM assay ( Figure 3) and ELISA assay (Figure 4).…”

AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia

“…AHSG inhibits insulin-stimulated insulin receptor autophosphorylation, insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS1), and the association of IRS1 with the p85 subunit of phosphatidylinositol-3 kinase in vitro (1-3). Elevated plasma AHSG was associated with insulin resistance in humans (4), and AHSG levels were higher in subjects with impaired glucose tolerance (5) and women with gestational diabetes (6). Ahsg knockout mice demonstrate increased basal and insulin-stimulated insulin receptor phosphorylation, increased glucose clearance, and insulin sensitivity (7).…”