Culler F L, Tung R F, Jansons R A, Mosier H D
Department of Pediatrics University of California, Irvine 92717, USA.
J Pediatr Endocrinol Metab. 1996 Jan-Feb;9(1):21-9. doi: 10.1515/jpem.1996.9.1.21.
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.
糖尿病妊娠（DP）中的婴儿巨大儿通常归因于胎儿高胰岛素血症。然而，母亲和胎儿体内的胰岛素样生长因子、它们的结合蛋白以及胎盘受体在胎儿过度生长过程中也可能发挥作用。我们测量了8例白人B级胰岛素依赖型糖尿病妊娠和8例非糖尿病妊娠（NP）的母血和脐血中胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子-II（IGF-II）、C肽、胰岛素样生长因子结合蛋白-1（IGFBP-1）、胰岛素样生长因子结合蛋白-2（IGFBP-2）和胰岛素样生长因子结合蛋白-3（IGFBP-3）的水平。这些结果与胎盘滋养层细胞膜受体（TR）对胰岛素（IN）、IGF-I和IGF-II的浓度及亲和力，以及婴儿和胎盘重量及母亲体重指数相关。糖尿病组和非糖尿病组在平均婴儿体重（4248±114 vs 3555±119 g，p<0.001）、胎盘重量（765±51 vs 575±24 g，p<0.01）、母亲体重指数（32.8±3.8 vs 21.3±1.2，p<0.02）、脐血IGF-I（136.8±6.6 vs 85.9±5.7 ng/ml，p<0.01）、脐血C肽（18.7±3.5 vs 9.0±1.7 ng/ml，p<0.025）、脐血IGFBP-1（21.9±4.7 vs 133.2±43.2 ng/ml，p<‘0.025）、脐血IGFBP-2（672.0±76 vs 1206±220 ng/ml，p<0.05）和脐血IGFBP-3（11.5±1.0 vs 5.6±0.6 ng/ml，p<0.001）方面存在显著差异。在脐血IGF-II、母血IGF-I、IGF-II、C肽、IGFBP-1、IGFBP-2和IGFBP-3，以及TR对IN、IGF-I和IGF-II的浓度及亲和力方面，糖尿病妊娠和非糖尿病妊娠之间未发现显著差异。方差分析显示婴儿体重与胎盘重量（p<0.01）、脐血IGF-I（p<0.02）、脐血C肽（p<0.01）和脐血IGFBP-3（p<0.01）之间存在交互作用。回归分析显示脐血IGF-I与脐血IGFBP-2值（r=-0.52，p=0.04）和IGFBP-3值（r=0.66，p<0.005）显著相关。母血IGF-I仅与母血IGFBP-3显著相关（r=0.65，p<0.01）。这些结果表明，胎儿胰岛素和IGF-I生成增加可能有助于糖尿病妊娠中婴儿巨大儿的发生。胎儿IGFBPs，特别是IGFBP-2和IGFBP-3生成的伴随变化可能调节胰岛素和IGFs的作用。胎盘滋养层受体对胰岛素、IGF-I和IGF-II的数量或结合亲和力缺乏变化，倾向于排除这些受体在胎儿巨大儿产生中的重要调节作用。
