Maternal and Fetal Placental Growth Hormone and IGF Axis in Type 1 Diabetic Pregnancy (original) (raw)
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Correction: Maternal and Fetal Placental Growth Hormone and IGF Axis in Type 1 Diabetic Pregnancy
PLoS ONE, 2012
Aim: Placental growth hormone (PGH) is a major growth hormone in pregnancy and acts with Insulin Like Growth Factor I (IGF-I) and Insulin Like Growth Hormone Binding Protein 3 (IGFBP3). The aim of this study was to investigate PGH, IGF-I and IGFBP3 in non-diabetic (ND) compared to Type 1 Diabetic (T1DM) pregnancies. Methods: This is a prospective study. Maternal samples were obtained from 25 ND and 25 T1DM mothers at 36 weeks gestation. Cord blood was obtained after delivery. PGH, IGF-I and IGFBP3 were measured using ELISA. Results: There was no difference in delivery type, gender of infants or birth weight between groups. In T1DM, maternal PGH significantly correlated with ultrasound estimated fetal weight (r = 0.4, p = 0.02), birth weight (r = 0.51, p,0.05) and birth weight centile (r = 0.41, p = 0.03) PGH did not correlate with HbA1c. Maternal IGF-I was lower in T1DM (p = 0.03). Maternal and fetal serum IGFBP3 was higher in T1DM. Maternal third trimester T1DM serum had a significant band at 16 kD on western blot, which was not present in ND. Conclusion: Maternal T1DM PGH correlated with both antenatal fetal weight and birth weight, suggesting a significant role for PGH in growth in diabetic pregnancy. IGFBP3 is significantly increased in maternal and fetal serum in T1DM pregnancies compared to ND controls, which was explained by increased proteolysis in maternal but not fetal serum. These results suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in T1DM pregnancies, which are at higher risk of macrosomia.
Introduction: Macrosomia in diabetic pregnancy is an ubiquitous finding and implies both maternal and fetal issues. Its incidence surpasses other critical obstetrical morbidity in diabetic pregnancy with increased placental size and polyhydramnios as comorbidity. The studies on the underlying factors contributing to macrosomia have focused on growth stimuli like IGF, glycemia, and insulin and their effects on regional organ function. IGF-I and –II in maternal serum are associated with birth weight and the bioavailabiliy is modulated by IGF-binding-proteins (IGFBP) and phosporylated isoforms of IGFBP and the presence of proteases and IGF split products. Human placental growth hormone regulates the effect of IGF-I in pregnancy. Methods: The literature on the IGF system′s possible effect on fetal growth in diabetic pregnancy is reviewed before our current studies and updated with respect to later findings. Regulation on bioavailability by proteolysis and phosporylation is described. The review discusses briefly the studies on pregnant women with type 1 diabetes with respect to vasculopathy. Results: The data show good correlation of IGF-1/2 levels with birth weight. No such correlation with IGFBP-1 and-3 is found. Fetal growth deviation in diabetic pregnancy is not uniform. In first trimester, growth delay is documented in fetal growth curves compared to non-diabetic controls. Accordingly, a shift in IGF-IGFBP regulation in second trimester is found with less proteolysis of IGFBPs and relative increase in total binding capacity. In third trimester, free IGF further increases as IGFBP binding decreases by proteolysis and modulation. The first trimester values may be used as predictor of fetal weight at term. Diabetic women show a two-to threefold increase in the in vitro IGFBP-3 proteolytic activity during pregnancy as compared to post-partum values. Conclusions: Prominent proteolysis of binding proteins and the modulation by insulin account for the mechanism leading to macrosomia. The two factors combined guarantee the stimulation by more bioavailable IGF and the glycemic levels reveal whether insulin dose are optimal. Structural factors of diabetes i.e. microangiopathy further modulate the sum of effects on fetal growth. In contrast to macrosomia, fetal growth restriction is associated with prominent maternal vascular endothelial complications, such as overt nephropathy, proliferative retinopathy, preeclampsia, and hypertension. In parallel to the growth inhibition, stimulatory effects are exerted by the GH axis including the placental growth hormones and occur probably as compensatory mechanism, similar to the increased IGFBP-3 proteolysis in late pregnancy found in growth retardation. This influence may in part explain the disproportionate growth in different tissue components occurring in the various stages of diabetic pregnancy.
World Journal of Advanced Research and Reviews
Introduction: During gestation, IGF1 secretion and availability in the maternal blood and at the maternal-fetal interface is mainly regulated by IGF-binding proteins (IGFBP) such as IGFBP-1 synthesized by the decidua. Data about the interaction between maternal, placental, and fetal IGF1/IGFBP in relation to fetal growth and newborn size during diabetic pregnancy (gestational Diabetes (GDM) and Type 1 DM (T1DM) is not clear. Aim of the study and Methods: We reviewed the research papers published in Pubmed, Google scholar, Research gate, and Scopus in the past 20 years on the relationship between maternal, placental, and fetal/infantile/ IGF1/IGFBP-1 in relation to birth size in pregnancies associated with maternal diabetes. Results: Twenty-eight research papers were selected and reviewed (patients’ number = 1902). In GDM pregnancies, higher maternal IGF1 levels and/or its availability due to lower IGFBP1 levels can increase the size (weight) and functions of the placenta. These incl...
The Journal of Clinical Endocrinology & Metabolism, 2003
In pregnancy, pituitary growth hormone (GH) is gradually replaced by placental growth hormone (hPGH). GH deficient pregnant women may take advantage of GH substitution during pregnancy, but this issue still remains unresolved. Also, in pregnancy diabetes may cause macrosomia. The combination of GH deficiency, GH substitution therapy and type 1 diabetes mellitus may influence pregnancy in unforeseen ways. We present a case of pregnancy in a GH deficient woman with type 1 diabetes who continued on GH replacement until week 21. In gestational week 37 a thin and mildly small-for gestational-age (length 55 cm, +3 SD, 99th centile and weight 2445 g., )1.4 SD, 10th centile) but otherwise healthy boy was born. The patient had levels of serum hPGH at the lower end of the range of values found in a matching group of diabetic women. Serum IGF-I levels were at the upper end of the range of values in the control group. A positive correlation between serum hPGH and IGF-I values was seen in the control group when using the area-under-the-curve (r ¼ 0:84; p < 0:001). The patientÕs child had lower birth weight and ponderal index, but was otherwise healthy. Serum IGF-I, but not hPGH, correlated to the absolute birth weight (r ¼ 0:63; p ¼ 0:015) and the birth weight z-score (r ¼ 0:55; p ¼ 0:039) in the control group. Serum hPGH and IGF-I declined rapidly after delivery. In conclusion, hPGH correlated to IGF-I in type 1 diabetes mellitus (DM), and IGF-I values correlated to the birth weight. Both type 1 diabetes mellitus and GH deficiency (with GH substitution therapy) may influence fetal growth, and in combination, the net influence may be difficult to predict.
The Journal of Clinical Endocrinology & Metabolism, 2000
We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28 -30 weeks gestation (K28) and 36 -38 weeks gestation (K36). The mean concentration (ϮSEM) of total PGH increased significantly from K28 to K36 (30.0 Ϯ 2.2 to 50.7 Ϯ 6.2
Journal of Clinical Endocrinology & Metabolism, 2000
We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28 -30 weeks gestation (K28) and 36 -38 weeks gestation (K36). The mean concentration (ϮSEM) of total PGH increased significantly from K28 to K36 (30.0 Ϯ 2.2 to 50.7 Ϯ 6.2
Pregnancy Hypertension, 2017
Objective: To investigate whether maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF) 1 and 2, and IGF binding proteins (IGFBP) 1 and 3 were altered in pregnancies complicated by later preeclampsia (PE). Study design: In a nested case-control study, PE cases (n=71) and matched controls (n=71) were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Maternal serum hormone concentrations at 20 weeks of gestation were determined by ELISA. Results: We found that maternal serum GH-V concentration at 20 weeks of gestation was unaltered in the PE group, compared to the control group (median, 1.78 ng/ml vs. 1.65 ng/ml, p = 0.884). Maternal IGF-1 and IGFBP-3 concentrations and the IGF-1/IGFBP-3 ratio in PE pregnancies were significantly higher than in controls (median, 253.1 ng/ml vs. 204.3 ng/ml, p < 0.0001; 8535 ng/ml vs. 7711 ng/ml, p = 0.0023; 0.032 vs. 0.026, p < 0.0001, respectively), whereas maternal IGFBP-1 concentration was significantly lower in PE pregnancies than in controls (median, 34.85 ng/ml vs. 48.92 ng/ml, p = 0.0006). Conclusion: Our findings suggest a potential role of IGFs and IGFBPs in the prediction of pregnancies complicated by PE. However, the maternal serum concentration of GH-V at 20 weeks' gestation is unlikely to be useful in the early prediction of PE.
Journal of Perinatal Medicine, 2010
Aims: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulinlike growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. Methods: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. Results: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery-32 completed weeks (Ps0.02). Conclusion: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery-32 completed weeks.
Early Human Development, 1997
A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained. IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 cases were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown.