Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community

Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1479-84. doi: 10.1161/ATVBAHA.110.203943. Epub 2010 Apr 8.

Abstract

Objective: The metabolic and genetic correlates of circulating insulin-like growth factor-1 (IGF-1) and its main circulating carrier, IGF-1-binding-protein-3 (IGFBP-3), are unclear.

Methods and results: We measured serum IGF-1 and IGFBP-3 concentrations in a sample of the Framingham Heart Study (N=3977, aged 40+/-9 years, 46% male) and evaluated their relations to cardiovascular risk factors using multivariable regression. Serum IGF-1 was inversely correlated with age, body mass index, total cholesterol, the presence of diabetes, alcohol consumption, and glomerular filtration rate (all P<0.01), whereas the ratio of IGF-1:IGFBP-3 was lower in women and inversely related to age, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, and alcohol consumption (all P<0.0001). Circulating IGF-1 correlated negatively with insulin resistance (homeostatic model assessment) (r=-0.1; P<0.0001) and was lower in participants with more components of the metabolic syndrome (Adult Treatment Panel III criteria) (P<0.0001). Additive genetic factors (heritability) accounted for 43% and 39% of the variation of IGF-1 and IGFBP-3, respectively (both P<10(-27)).

Conclusions: Our cross-sectional observations in a large community-based sample link lower circulating IGF-1 to greater metabolic risk burden and underscore substantial genetic influences on IGF-1 concentrations. Prospective studies are warranted to elucidate whether lower IGF-1 concentrations predict greater metabolic risk longitudinally.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cross-Sectional Studies
  • Female
  • Genetic Testing
  • Genome-Wide Association Study
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / blood*
  • Insulin-Like Growth Factor I / analysis*
  • Linear Models
  • Male
  • Middle Aged
  • Pedigree
  • Quantitative Trait, Heritable
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology

Substances

  • Biomarkers
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I