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


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.
Lam
Carolyn S P
CS
National Heart, Lung, and Blood Institute's Framingham Heart Study, 73 Mount Wayte Avenue, Framingham, MA 01702, USA.
Chen
Ming-Huei
MH
Lacey
Sean M
SM
Yang
Qiong
Q
Sullivan
Lisa M
LM
Xanthakis
Vanessa
V
Safa
Radwan
R
Smith
Holly M
HM
Peng
Xuyang
X
Sawyer
Douglas B
DB
Vasan
Ramachandran S
RS
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003430:Cross-Sectional Studies; D005260:Female; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I