AGING IS ASSOCIATED WITH DECREASED SUPPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 BY INSULIN

We determined whether aging influences circulating insulin-like growth factor-binding protein-1 (IGFBP-1) concentrations and, if so, whether this effect is explained by altered regulation of IGFBP-1 by insulin. Fasting levels of glucose, insulin, and IGFBP-1 were measured in 94 healthy volunteers, ages 24-93 yr. To determine the effect of aging on insulin-induced suppression of IGFBP-1, an oral glucose tolerance test (OGTT) was performed in 10 older (72-92 yr) and 10 younger (24-58 yr) nonobese subjects, matched for sex and body mass index. For all ages combined, the mean glucose level (+/-SE) averaged 4.9 +/- 0.1 mmol/L, and there was no significant change with aping. Fasting insulin and IGFBP-1 concentrations increased with advancing age (r = 0.37, P < 0.001 for age vs. insulin and r = 0.47, P < 0.001 for age vs. IGFBP-1). However, there was no correlation between insulin and IGFBP-1 concentrations. In multiple linear regression analysis, the age-related increase in IGFBP-1 was independent of body mass index. During the OGTT, the mean insulin concentration was significantly higher in the older group compared with the younger group (P < 0.001). Serum IGFBP-1 concentrations were higher in the fasting state as well as during the OGTT, and the mean percent decrease of IGFBP-1 below baseline was significantly smaller in the older compared to the younger subjects at 3 h (35 +/- 5% vs. 55 +/- 2%, P < 0.01). We conclude that aging is associated with decreased suppression of serum IGFBP-1 by insulin, as demonstrated by 1) lack of the inverse correlation between fasting insulin and IGFBP-1 seen in young adults; 2) concurrent elevation of fasting insulin and IGFBP-1 concentrations; and 3) a blunted decrease in serum IGFBP-1 during an OGTT.