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Bioactive IGF-I in Obesity |
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AbstractContext: In obesity, total IGF-I is not reduced to the degree predicted by low GH levels, and free IGF-I levels are normal to high. Total and free IGF-I may not reflect IGF-I biologic activity, as immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor.Objective: To investigate the biologic activity of IGF-I in obesityDesign: Cross-sectionalSetting: General Clinical Research CenterStudy Participants: 34 healthy women: 11 lean, 12 overweight, and 11 obese women of comparable mean age (overall mean 30.7 +/- 1.3 y).Intervention: NoneMain Outcome Measures: Bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1 and GH, using 6h pools of serum collected every 10 min for 24h, and fasting IGF-I and IGFBP-3.Results: Mean 24h GH (R= -0.76, p<0.0001), total IGF-I (R = -0.36, p=0.04) and IGFBP-1 (R= -0.41, p=0.017) levels were inversely associated with BMI, whereas bioactive IGF-I and IGFBP-3 levels were not. Mean bioactive IGF-I was similar in the groups [0.96+/-0.09 (lean), 1.08+/-0.09 (overweight), 0.84+/-0.11 (obese) |f9g/l, overall p=0.22]. Percent bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese than both lean and overweight subjects (p=0.039).Conclusions: Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24h mean bioactive IGF-I levels are not reduced in obese women and do not correlate with BMI or IGFBP-1 levels. This argues against elevated bioactive IGF-I as the etiology of reduced GH secretion through a feedback mechanism in obesity. 10.1210/jc.2009-0614
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