Abstract
Lower level of insulin-like growth factor-binding protein (IGFBP-1) has been observed in insulin resistance, while higher level of matrix metalloproteinase-8 (MMP-8) has been linked to obesity. The aim here was to study in overweight and obese women, typically manifesting with insulin resistance, whether IGFBP-1 and MMP-8 are related to and reflect systemic low-grade inflammation, metabolism and diet. Fasting serum from overweight and obese pregnant women (n = 100) in early pregnancy were analysed for IGFBP-1, phosphorylated IGFBP-1 (phIGFBP-1) and MMP-8. High-sensitivity CRP and GlycA were used as markers for low grade inflammation. GlycA and lipids were quantified using NMR. IGFBP-1 associated negatively with GlycA, evidenced by higher concentrations in the lowest quartile (median 1.53 (IQR 1.45–1.72)) compared to the highest (1.46 (1.39–1.55)) (P = 0.03). Several lipid metabolites, particularly HDL-cholesterol, correlated inversely with phIGFBP-1 (FDR<0.1). Nutritional status and diet contributed to the levels of IGFBP-1, demonstrated as an inverse correlation with maternal weight (Spearman r = -0.205, P = 0.04) and dietary intake of vitamin A (r = -0.253, P = 0.014) and a direct correlation with dietary intake of polyunsaturated fatty acids (Spearman r = 0.222, P = 0.03). MMP-8 correlated inversely with pyridoxine (r = -0.321, P = 0.002) and potassium (r = -0.220, P = 0.033). Maternal serum IGFBP-1 may contribute to maternal lipid metabolism in overweight and obese women during early pregnancy. These findings may be of importance in identification of metabolic disturbances preceding the adverse metabolic outcomes in pregnancy.
Highlights
Insulin-like growth factor binding protein 1 (IGFBP-1) regulates the half-life and activity of IGF-I and II, with multiple actions on host metabolism and cell growth [1]
IGFBP-1 produced by the liver binds only to a small fraction of circulating IGF-1, it is of importance as it’s hepatic production is suppressed by food intake, and subsequently increased glucose and insulin concentrations
No correlations were observed between prepregnancy BMI (P > 0.063, for all) or body fat percentage (P > 0.085 for all) and IGFBP-1, phIGFBP-1 or matrix metalloproteinase-8 (MMP-8) levels
Summary
Insulin-like growth factor binding protein 1 (IGFBP-1) regulates the half-life and activity of IGF-I and II, with multiple actions on host metabolism and cell growth [1]. IGFBP-1 produced by the liver binds only to a small fraction of circulating IGF-1, it is of importance as it’s hepatic production is suppressed by food intake, and subsequently increased glucose and insulin concentrations. At a fasting condition, the production of IGFBP-1 is increased [2]. In addition to systemic effects, both IGF-1 and IGFBP-1 exert profound local roles during pregnancy due to their involvement in implantation and fetal growth. Elevated IGFBP-1 concentrations have been detected in preeclampsia, with both decidua and liver likely contributing to its production [3].
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