Inverse changes in fetal insulin-like growth factor (IGF)-1 and IGF binding protein-1 in association with higher birth weight in maternal diabetes

Objective The insulin like growth factor (IGF) system plays a key role in regulating fetal growth, is metabolically regulated, and may influence development of increased birth weight in offspring of mothers with diabetes. We examined IGF-1 and IGF binding protein-1 (IGFBP-1) concentrations in cord blood samples from offspring of mothers with gestational and type 2 diabetes. Design and patients Case-control study of Maori and Pacific Island mothers recruited prospectively at Middlemore Hospital, South Auckland, New Zealand. Measurements Cord blood (for insulin, IGF-1 and IGFBP-1) was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation from138 mothers with gestational diabetes (GDM), 39 mothers with type 2 diabetes (T2DM) and 95 control mothers. Results Babies born to mothers with both GDM and T2DM had significantly increased birth weight (Z-score birth weight mean +/- SD: GDM 0.94 +/- 1.31, T2DM 0.53 +/- 1.1) compared to controls (Z-score birth weight -0.08 +/- 1.10). IGFBP-1 was significantly reduced in both diabetic groups (median interquartile range: GDM 67(31-137) ng/ml, T2DM 59(29-105) ng/ml, control 114(56-249) ng/ml). Cord IGF-1 was significantly increased in cord blood of infants of mothers with GDM (42.2 +/- 16.3 ng/ml vs. control 34.7 +/- 18.5 ng/ml) but not T2DM (38.7 +/- 17.4 ng/ml). In all offspring, IGF-1 and IGFBP-1 were positively and negatively correlated with birth weight, respectively. Conclusions Maternal diabetes results in inverse changes of circulating fetal IGF-1 and IGFBP-1 at birth. A decrease in circulating IGFBP-1 and to a lesser extent an increase in circulating IGF-1 may present an important mechanism that contributes to increased birth weight in diabetic pregnancies.