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Bioactive insulin-like growth factor-I in obesity
J Frystyk1, D J Brick, A V Gerweck
1Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, MA 02114, USA.
Context:
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 biological activity because immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor.
Objective:
The aim of the study was to investigate the biological activity of IGF-I in obesity.
Design And Setting:
We conducted a cross-sectional study at a General Clinical Research Center.
Study Participants:
Thirty-four healthy women (11 lean, 12 overweight, and 11 obese) of comparable age (overall mean, 30.7 +/- 1.3 yr) participated in the study.
Intervention:
There were no interventions.
Main Outcome Measures:
We measured bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1, and GH using 6-h pools of serum collected every 10 min for 24 h, and fasting IGF-I and IGFBP-3.
Results:
Mean 24-h GH (R = -0.76; P < 0.0001), total IGF-I (R = -0.36; P = 0.040), 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 [2.72 +/- 0.22 (lean), 3.10 +/- 0.32 (overweight), and 2.43 +/- 0.23 [corrected] (obese) microg/liter; overall P = 0.22]. Percentage bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese subjects than both lean and overweight subjects (P = 0.039).
Conclusions:
Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24-h 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.
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