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Bioactive Insulin-Like Growth Factor-I in Obesity

Medical Research Laboratories and Medical Department M (J.F.), Aarhus University Hospital, DK-8000 Aarhus, Denmark; Neuroendocrine Unit (D.J.B., A.V.G., K.K.M.), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; and Department of Endocrinology (A.L.U.), Vanderbilt University, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Karen K. Miller, Neuroendocrine Unit, Bulfinch 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: KKMiller{at}Partners.org.

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 [0.96 ± 0.09 (lean), 1.08 ± 0.09 (overweight), and 0.84 ± 0.11 (obese) µg/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.