Serum Insulin-Like Growth Factor-1 Binding Proteins 1 and 2 and Mortality in Older Adults: The Health, Aging, and Body Composition Study

OBJECTIVE To evaluate the relationship between serum insulin-like growth factor 1 (IGF-1), IGF-1 binding protein 1 (IGFBP-1), and IGF-1 binding protein 2 (IGFBP-2) and fasting insulin, fasting glucose, adiposity, and mortality in older adults. DESIGN A prospective cohort study with mean follow-up of 6.2 years. SETTING Participants were recruited and followed at two centers affiliated with academic medical institutions. PARTICIPANTS Six hundred twenty-five men and women aged 70 and older and in good health at the time of enrollment. MEASUREMENTS Serum IGF-1, IGFBP-1, and IGFBP-2; fasting serum insulin; fasting serum glucose; visceral fat; and total percent fat. RESULTS Higher IGFBP-1 and higher IGFBP-2 were significantly associated with lower fasting insulin, lower fasting glucose, and lower adiposity, but higher IGFBP-1 and IGFBP-2 were associated with greater mortality. In multivariate adjusted models, the hazard ratio for all-cause mortality was 1.48 (95% confidence interval (CI)=1.14-1.92) per standard deviation (SD) increase in IGFBP-2 and 1.34 (95% CI=1.01-1.76) per SD increase in IGFBP-1. No association was found between IGF-1 and all-cause mortality. CONCLUSIONS Higher IGFBP-1 and IGFBP-2 are associated with lower adiposity and decreased glucose tolearance but also with greater all-cause mortality. Higher levels of serum IGF-1 binding protein (IGFBP) may indicate greater IGF-1 activity and thus represent an association between higher IGF-1 activity and mortality in humans.