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

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Abstract
Summary: 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.