title: Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency.
abstract: BACKGROUND
  Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear.
  
  
  OBJECTIVE
  Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation.
  
  
  METHODS
  This was a double-blind, placebo-controlled, parallel, 3-month study.
  
  
  METHODS
  Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood samples were collected at baseline, and months 1 and 3, whereas 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.
  
  
  METHODS
  Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11β-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.
  
  
  CONCLUSIONS
  Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopic fat 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition (K.C.J.Y., C.T.R., B.J.K., J.Q.P.), Department of Medicine, and Advanced Imaging Research Center (W.D.R., J.R.P.), Oregon Health and Science University, Portland, Oregon 97239; Oregon National Primate Research Center (C.T.R.), Beaverton, Oregon 97006; and Institute of Clinical Medicine N (J.F.), Aarhus University, DK-8000 Aarhus, Denmark.
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: Charles T
authors.initials: CT
authors.lastname: Roberts
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: William D
authors.initials: WD
authors.lastname: Rooney
authors.forename: James R
authors.initials: JR
authors.lastname: Pollaro
authors.forename: Bethany J
authors.initials: BJ
authors.lastname: Klopfenstein
authors.forename: Jonathan Q
authors.initials: JQ
authors.lastname: Purnell
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D006854:Hydrocortisone