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

J Clin Endocrinol Metab. 2009 Apr;94(4):1386-92. doi: 10.1210/jc.2008-1430. Epub 2009 Jan 21.


Context: IGF binding protein (IGFBP)-1 is the only acute regulator of IGF-I bioavailability. Its production is suppressed by insulin, and low levels are associated with hyperinsulinemia and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Birth Weight
  • Body Height / genetics
  • Child
  • DNA Primers
  • Female
  • Glucose Tolerance Test
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Insulin-Like Growth Factor I / genetics
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Puberty
  • Reference Values
  • Triglycerides / blood
  • Young Adult


  • DNA Primers
  • Insulin-Like Growth Factor Binding Protein 1
  • Triglycerides
  • Insulin-Like Growth Factor I

Associated data

  • ISRCTN/ISRCTN18062389
  • ISRCTN/ISRCTN65230311
  • ISRCTN/ISRCTN96883876