Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone

Abstract

OBJECTIVES:We investigated the effect of obesity on the serum levels of total and free IGF-1 and their relationship to the circulating levels of insulin and IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study included 43 obese subjects (ideal body weight; IBW b 120%) and 45 controls (IBW`100%). All of the subjects were male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, and insulin were measured in obese subjects and normal control subjects. RESULTS: No signi®cant differences in the circulating levels of total and IGFBP-3 were observed between the obese and control groups. In contrast to total IGF-1, free IGF-1 in obese subjects was signi®cantly increased compared to normal controls (P`0.05). Serum total and free IGF-1 were inversely correlated with age (r À0.42, P 0.001, and À0.44, P 0.001). Fasting serum insulin concentrations were elevated in all the obese subjects (P`0.05) and positively correlated with IBW (r 0.57, P 0.001). The levels of serum GH and IGFBP-1 were suppressed in all the obese subjects (P`0.05). IGFBP-1 was inversely correlated with IBW (r À0.51, P 0.001) and serum insulin concentrations (r À0.48, P 0.001). The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r À0.48, P 0.001). Using multiple linear regression analysis, total IGF-1 and insulin concentrations were positively correlated (r 0.58, P 0.001) and free IGF-1 and IGFBP-1 concentrations were negatively correlated (r À0.57, P 0.001). CONCLUSION: We con®rmed that total IGF-1 and IGFBP-3 concentrations were not signi®cantly different between the obese and control groups, despite GH hyposecretion in obesity. We also found that free IGF-1 concentrations were higher in obese subjects than in normal controls. It seems likely that overnutrition and chronic hyperinsulinaemia in obesity may alter this regulated growth response by insulin stimulation of IGF-1 production and suppression of hepatic IGFBP-1 and IGFBP-2 production, which may inhibit IGF-1 bioactivity.

Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial

“…The increases in IGFBP-1 and -2 most likely caused a reduction in circulating free IGF-IFa small fraction of circulating IGF-I that is not bound by any IGF-binding protein, and that probably reflects the fraction most rapidly available to tissues for binding to cellular receptors. Other studies (Frystyk et al, 1995;Nam et al, 1997;Nyomba et al, 1997) have shown inverse correlations of plasma IGFBP-1 and -2 with plasma free IGF-I levels. Unfortunately, we had technical problems with an assay kit for measurement of free IGF-I, and thus All P-values are adjusted for treatment/intervention status, age class, insulin level, testosterone level.…”

Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database

“…For example, serum insulin and IGF-I levels are elevated in obesity. 15,16 Insulin and IGF-I activate the mTOR-AKT pathway, resulting in increased proliferation and decreased apoptosis. 17 In animals, dietary-induced increased serum IGF-I and insulin levels are associated with increased PC growth.…”

Body mass index, waist circumference and waist–hip ratio and serum levels of IGF-I and IGFBP-3 in European women

“…In chronically hyperinsulinemic states, such as obesity, insulin inhibits the synthesis of IGFBP-1 and -2 and increases the free IGF-I fraction. 51,52 Insulin also increases free circulating IGF-I by downregulating the synthesis of IGF-binding proteins-1 and -2 which, together with IGFBP-3, play an important role in regulating the free fraction of IGF-I. In turn, increased free IGF-I exerts a negative feedback on pituitary GH secretion, the primary stimulus for hepatic IGF-I synthesis and causes a decrease in total IGF-I levels.…”