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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Loukovaara
M
M
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland. mikko.loukovaara@hus.fi
Leinonen
P
P
Teramo
K
K
Nurminen
E
E
Andersson
S
S
Rutanen
E-M
EM
D000328:Adult; D001724:Birth Weight; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D010766:Phosphorylation; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood*; D011254:Pregnancy in Diabetics / Q000097:blood*; D020033:Protein Isoforms / Q000097:blood
C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D011257:Pregnancy Proteins; D020033:Protein Isoforms