Context: IGF binding protein (IGFBP)-I is the only acute regulator of IGF-I bioavailability. Its production is suppressed by insulin, and low levels are associated with hyperinsulinemiaand cardiovascular disease risk in adults. Data on IGFBP-1 levels in short, small for gestational age (SGA) subjects are scarce, and associations with IGFBP1 promoter single nucleotide polymorphisms have not been established. Objective: The aim of the study was to determine IGFBP-1 levels in short SGA subjects compared with those in controls, to assess genotype frequency of the -575 G/A single nucleotide polymorphism, and to determine its impact on IGFBP-1 levels. Subjects: A total of 272 short subjects born SGA and 330 subjects with normal stature (245 children, 85 young adults) participated in the study. Outcome Measures: We measured fasting levels of IGFBP-1, IGF-I, insulin and lipid parameters, and body composition. Results: IGFBP-1 sd score (SDS) was comparable to controls in lean, short, SGA children but significantly lower in short SGA adults with normal fat mass (P <0.001). IGFBP-1 SDS correlated significantly with insulin levels, systolic blood pressure SDS, and various lipid parameters. Baseline IGFBP-1 SDS was lowest in SGA children with-575 GG genotype and significantly higher in SGA children with one or two copies of the A allele. In response to a given insulin level, children with the AA genotype had a significantly higher IGFBP-1 SDS compared to children with the GG genotype. Conclusion: Normal IGFBP-1 levels in lean, short, SGA children may reflect a normal metabolic state, despite reported hyperinsulinemia. IGFBP-1 is modulated by polymorphic variability and seems to be an additional player in the complex interaction between the IGF-IGFBP axis, glucose homeostasis, and lipid metabolism. Copyright

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van Kaay, D.D, Deal, C.L, de Kort, S.W.K, Willemsen, R.H, Leunissen, R.W.J, Ester, W.A, … Hokken-Koelega, A.C.S. (2009). Insulin-like growth factor-binding protein-1: Serum levels, promoter polymorphism, and associations with components of the metabolic syndrome in short subjects born small for gestational age. Journal of Clinical Endocrinology and Metabolism, 94(4), 1386–1392. doi:10.1210/jc.2008-1430