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

OBJECTIVES: We investigated the effect of obesity on the serum levels of total and free IGF-1 and their relationship to the circulating leve ls of insulin and IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study included 43 obese subjects (ideal body we ight; IBW > 120%) and 45 controls (IBW < 100%). All of the subjects we re male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP-1, IGFBP-2, IGFBP -3, and insulin were measured in obese subjects and normal control sub jects. RESULTS: No significant differences in the circulating levels o f 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 signifi cantly increased compared to normal controls (P < 0.05). Serum total a nd free IGF-1 were inversely correlated with age (r= -0.42, P= 0.001, and -0.44, P= 0.001). Easting serum insulin concentrations were elevat ed in all the obese subjects (P < 0.051 and positively correlated with IBW (r= 0.57, P= 0.001). The levels of serum GH and IGFBP-1 were supp ressed in all the obese subjects (P<0.05). IGEBP-1 was inversely corre lated with IBW (r=-0.51, P=0.001) and serum insulin concentrations (r= -0.48, P=0.001), The IGFBP-2 concentrations were also suppressed in o bese subjects and inversely related to free IGF-1 (r= -0.48, P= 0.001) . Using multiple linear regression analysis, total IGF-1 and insulin c oncentrations were positively correlated (r=0.58, P=0.001) and free IG F-1 and IGEBP-1 concentrations were negatively correlated (r= -0.57, P = 0.001). CONCLUSION: We confirmed that total IGF-1 and IGEBP-3 concen trations were not significantly different between the obese and contro l groups, despite GH hyposecretion in obesity. We also found that free IGF-1 concentrations were higher in obese subjects than in normal con trols. It seems likely that overnutrition and chronic hyperinsulinaemi a in obesity may alter this regulated growth response by insulin stimu lation of IGF-1 production and suppression of hepatic IGFBP-1 and IGFB P-2 production, which may inhibit IGF-1 bioactivity.