Mette Bjerre

The effect of growth hormone on bioactive IGF in overweight/obese women

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  • Laura E Dichtel, Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States. Electronic address: ldichtel@partners.org.
  • ,
  • Mette Bjerre
  • Melanie Schorr, Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
  • ,
  • Miriam A Bredella, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.
  • ,
  • Anu V Gerweck, B Biller, Neuroendocrine Unit, Massachusetts General Hospital, Boston, 02114-2096, United States.
  • ,
  • Brian M Russell, B Biller, Neuroendocrine Unit, Massachusetts General Hospital, Boston, 02114-2096, United States.
  • ,
  • Jan Frystyk
  • Karen K Miller, Neuroendocrine Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States.

OBJECTIVE: Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration.

DESIGN: Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured.

RESULTS: Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p < 0.0001) and bioactive IGF (1.29 ± 0.39 to 2.60 ± 1.12 μg/L, p < 0.0001). The treatment-related increase in bioactive IGF, but not total IGF-I concentration, predicted an increase in lean mass (r = 0.31, p = 0.03) and decrease in total adipose tissue/BMI (r = -0.43, p = 0.003).

CONCLUSIONS: Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes.

CLINICAL TRIAL REGISTRATION NUMBER: NCT00131378.

OriginalsprogEngelsk
TidsskriftGrowth Hormone & I G F Research
Vol/bind40
Sider (fra-til)20-27
Antal sider8
ISSN1096-6374
DOI
StatusUdgivet - jun. 2018

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