Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency

Kevin C.J. Yuen, Charles T. Roberts, Jan Frystyk, William D. Rooney, James R. Pollaro, Bethany J. Klopfenstein, Jonathan Q. Purnell

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopicfat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting insulin-like effects through the abundant muscle IGF-1 receptors, but this hypothesis requires confirmation with further studies.

Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study.

Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.

Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.

Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood sampleswere collected at baseline, and months 1 and 3, where as hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3.

Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11 β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated.

Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P<.01) and IGF-1 to IGFBP-3 molar ratio (P <.05), but fasting glucose, insulin, C-peptide, free fatty acid, adiponectin, IGF-1 bioactivity, IGF-2, IGFBP-2, 24-hour CPRs, adipocyte size, adipocyte 11β-hydroxysteroid dehydrogenase activity, intrahepatic lipid, extramyocellular, or intramyocellular were unchanged. In the placebo group, all within-group parameters from months 1 and 3 compared with baseline were unchanged.

Original languageEnglish (US)
Pages (from-to)E1862-E1869
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number10
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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