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

Lam CS, Chen MH, Lacey SM, Yang Q, Sullivan LM, Xanthakis V, Safa R, Smith HM, Peng X, Sawyer DB, Vasan RS
Arterioscler Thromb Vasc Biol. 2010 30 (7): 1479-84

PMID: 20378848 · PMCID: PMC2891230 · DOI:10.1161/ATVBAHA.110.203943

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.

MeSH Terms (19)

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

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