Effect of maternal diabetes on phosphorylation of insulin‐like growth factor binding protein‐1 in cord serum

Abstract

The insulin-like growth factor (IGF) system is considered important in the regulation of fetal growth. Binding of IGFs to specific binding proteins (IGFBPs) modifies their actions. In fetal blood, IGFBP-1 is the primary IGF binding protein whose phosphorylation generates proteins with different affinities for IGF-I. We studied cord serum IGFBP-1 phosphoisoform profiles in normal pregnancies and in diabetic pregnancies, which are frequently complicated by macrosomia. Cord serum IGFBP-1 phosphoisoform concentrations were measured at birth by two immunoenzymometric assays in 67 pregnancies complicated by Type 1 diabetes, in 28 pregnancies complicated by insulin-treated gestational diabetes, and in 62 normal pregnancies. Cord serum highly phosphorylated IGFBP-1 (hpIGFBP-1) concentrations were lower in pregnancies complicated by Type 1 diabetes (204 +/- 36 microg/l, P = 0.032) and in pregnancies complicated by gestational diabetes (170 +/- 28 microg/l, P = 0.031) than in controls (316 +/- 34 microg/l). Cord serum lesser phosphorylated IGFBP-1 (lpIGFBP-1) concentrations were similar in diabetic and normal pregnancies (P = 0.692 between groups by analysis of variance). Relative birth weight correlated negatively with cord serum hpIGFBP-1 and lpIGFBP-1 in diabetic pregnancies, and with cord serum lpIGFBP-1 in normal pregnancies. Maternal diabetes is associated with suppressed hpIGFBP-1 but unaltered lpIGFBP-1 concentrations in cord serum, suggesting that IGFBP-1 phosphoisoforms are differentially regulated in the fetus. Because hpIGFBP-1 has a higher affinity for IGF-I than does lpIGFBP-1, diabetes-related changes in fetal IGFBP-1 phosphorylation may increase IGF-I bioavailability and, consequently, stimulate fetal growth. This may partly explain the increased occurrence of macrosomia in diabetic pregnancies.