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 Roberts, Jan Frystyk, William Rooney, James R. Pollaro, Bethany Klopfenstein, Jonathan 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

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

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ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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