Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures.

Abstract

Reduced secretion of GH and production of insulin-like growth factor I (IGF-I) contribute to altered body composition in human aging. IGF-binding proteins (IGFBPs) are important modulators of IGF action, yet little is known regarding their role and regulation in aging. Accordingly, we measured levels of IGFBP-1, an important short term modulator of IGF bioavailability that is suppressed by insulin, and levels of IGFBP-3, the major circulating IGF carrier protein, and examined their relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures in old (63-89 yr) and young (23-39 yr) men. Serum levels of IGFBP-1 were increased 3-fold in old vs. young men despite high insulin levels in elders. Nevertheless, IGFBP-1 and insulin levels correlated in old and young men (r = - 0.49; P < 0.002 and r = -0.42; P < 0.025), suggesting that insulin continues to play an important role in the regulation of IGFBP-1 in aging. Glucose levels also were significantly inversely related to IGFBP-1 in old and young men (r = 0.37; P = 0.02 and r = -0.49; P < 0.01), and this relationship was not accounted for by the effect of insulin. IGF-I levels were reduced by 33% in elders (P < 0.001) and correlated with IGFBP-1 levels among old (r = -0.40; P < 0.01), but not young, men, indicating that low GH secretion and/or IGF-I production may contribute to the elevation of IGFBP-1 levels in aging. IGFBP-3 levels were reduced among elders, but not to the same extent as IGF-I, resulting in a relative excess of IGFBP-3 in elders (IGFBP-3/IGF-I ratio, 20.1 +/- 0.9 vs. 15.4 +/- 1.0; P < 0.001). The IGFBP-3/IGF-I ratio correlated with IGF-I levels in young and old men (r = -0.79; P < 0.001 and r = -0.82; P < 0.001), indicating that diminished GH secretion also may contribute to a relative excess of IGFBP-3 among elders. Dehydroepiandrosterone sulfate levels were low in elders, but did not correlate with IGF, IGFBP, insulin, or glucose levels in either age group. Serum levels of IGFBP-1 (but not IGF-I or -II or IGFBP-3) correlated with body mass index and upper arm fat and muscle areas in elders. These relationships were accounted for by the effects of insulin, suggesting that regulation of IGFBP-1 by insulin may play a role in determining body composition in aging. We conclude that insulin remains an important determinant of IGFBP-1 levels in elders, that the fasting glucose level is also a significant determinant of IGFBP-1 in both old and young subjects, and that reduced secretion of GH may contribute to impaired anabolism in aging through multiple mechanisms, including reduced production of IGF-I and alterations in circulating levels of both IGFBP-1 and -3. These findings are consistent with the concept that alterations in IGFBP levels may contribute to changes in IGF bioavailability and body composition in aging.