No decrease in free IGF-I with increasing insulin in obesity-related insulin resistance

Objective: Different facts suggest that the insulin growth factor (IGF)/ insulin growth factor-binding protein (IGFBP) system may be regulated by factors other than growth hormone. It has been proposed that, in healthy subjects, free IGF-I plays a role in glucose metabolism. The role of free IGF-I in glucose homeostasis in insulin resistance is poorly understood. This study was undertaken to evaluate the effects of acute changes in plasma glucose and insulin levels on free IGF-I and IGFBP-1 in obese and non-obese subjects. Research Methods and Procedures: Nineteen lean and 24 obese subjects were investigated. A frequently sampled intravenous glucose tolerance test was performed. Free IGF-I and IGFBP-1 were determined at 0, 19, 22, 50, 100, and 180 minutes. Results: Basal free IGF-I levels tended to be higher and IGFBP-1 lower in obese than in lean subjects. IGFBP-1 levels inversely correlated with basal insulin concentration. To determine the effects of insulin on the availability of free IGF-I and IGFBP-1, changes in their plasma concentrations were measured during a frequently sampled intravenous glucose tolerance test. After insulin administration, a significant suppression of free IGF-I at 22% was observed in lean subjects. In contrast, plasma-free IGF-I levels remained essentially unchanged in the obese group. The differences between both groups were statistically significant at 100 minutes (p < 0.01) and 180 minutes (p < 0.05). Serum IGFBP-1 was suppressed to a similar extent in both groups. Discussion: These data suggest that the concentrations of free IGF-I and IGFBP-1 are differentially regulated by obesity. Obesity-related insulin resistance leads to unsuppressed free IGF-I levels.