Growth promoting peptides in diabetic and non-diabetic pregnancy: interactions with trophoblastic receptors and serum carrier proteins.
Infantile macrosomia in diabetic pregnancy (DP) is commonly attributed to fetal hyperinsulinism. However, insulin-like growth factors in the mother and the fetus, their binding proteins and their placental receptors may also play roles in the process of fetal overgrowth. We measured levels of maternal and cord serum IGF-I, IGF-II, C-peptide, IGFBP-1, IGFBP-2 and IGFBP-3 in 8 White Class B insulin dependent DP and 8 non-diabetic pregnancies (NP). These results were correlated with the concentration and affinity of placental trophoblastic membrane receptors (TR) for insulin (IN), IGF-I and IGF-II as well as with infant and placenta weights and maternal body mass indices. Significant respective differences between the diabetic and non-diabetic groups were found in mean infant weight, 4248 +/- 114 vs 3555 +/- 119 g (p < 0.001), placental weight 765 +/- 51 vs 575 +/- 24 g (p < 0.01), maternal body mass index 32.8 +/- 3.8 vs 21.3 +/- 1.2 (p < 0.02), cord serum IGF-I 136.8 +/- 6.6 vs 85.9 +/- 5.7 ng/ml (p < 0.01), cord serum C-peptide 18.7 +/- 3.5 vs 9.0 +/- 1.7 ng/ml (p < 0.025), cord serum IGFBP-1 21.9 +/- 4.7 vs 133.2 +/- 43.2 ng/ml (p < 0.025), cord serum IGFBP-2 672.0 +/- 76 vs 1206 +/- 220 ng/ml (p < 0.05) and cord serum IGFBP-3 11.5 +/- 1.0 vs 5.6 +/- 0.6 ng/ml (p < 0.001). No significant differences were found between DP and NP with respect to cord serum IGF-II, maternal serum IGF-I, IGF-II, C-peptide, IGFBP-1, IGFBP-2 and IGFBP-3, and the concentration and affinity of TR for IN, IGF-I and IGF-II. Analysis of variance revealed an interaction between infant weight and the weight of the placenta (p < 0.01), cord IGF-I (p < 0.02), cord C-peptide (p < 0.01) and cord IGFBP-3 (p < 0.01). Regression analysis revealed significant correlations of cord IGF-I with cord values of IGFBP-2 (r = -0.52, p = 0.04) and IGFBP-3 (r = 0.66, p < 0.005). Maternal serum IGF-I significantly correlated only with maternal IGFBP-3 (r = 0.65, p < 0.01). These results suggest that increased fetal production of insulin and IGF-I may contribute to the development of infantile macrosomia in DP. Concomitant changes in fetal production of IGFBPs, particularly IGFBP-2 and IGFBP-3, may modulate the action of insulin and IGFs. The lack of change in number or binding affinity of placental trophoblastic receptors for insulin, IGF-I and IGF-II tends to exclude a significant regulatory role of these receptors in the production of fetal macrosomia.
Culler
F L
FL
Department of Pediatrics University of California, Irvine 92717, USA.
Tung
R F
RF
Jansons
R A
RA
Mosier
H D
HD
D000328:Adult; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*
D002096:C-Peptide; D002352:Carrier Proteins; D006133:Growth Substances; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D017978:Receptors, Growth Factor; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II