title: Continuous positive airway pressure increases pulsatile growth hormone secretion and circulating insulin-like growth factor-1 in a time-dependent manner in men with obstructive sleep apnea: a randomized sham-controlled study.
abstract: OBJECTIVE
  To assess the time-dependent effect of continuous positive airway pressure (CPAP), on insulin-like growth factor-1 (IGF-1), IGF binding proteins (IGFBPs) and pulsatile growth hormone (GH) secretion.
  
  
  METHODS
  A randomized, double-blind, sham-controlled, parallel group study.
  
  
  METHODS
  Sixty-five middle-aged men with moderate to severe obstructive sleep apnea.
  
  
  METHODS
  Active (n = 34) or sham (n = 31) CPAP for 12 weeks, followed by 12 weeks of active CPAP (n = 65).
  
  
  RESULTS
  Fasting morning IGF-1, IGFBP-3, and IGFBP-1 blood levels at 0, 6, 12, and 24 weeks. Overnight GH secretion was calculated by mathematical deconvolution of serial GH measurements from serum samples collected every 10 min (22:00-06:00) during simultaneous polysomnography in a subset of 18 men (active n = 11, sham n = 7) at week 12. Active, compared with sham, CPAP increased IGF-1 at 12 weeks (P = 0.006), but not at 6 weeks (P = 0.44). Changes in IGFBP-3 and IGFBP-1 were not different between groups at 6 or 12 weeks (all P ≥ 0.15). At week 24, there was a further increase in IGF-1 and a decrease in IGFBP-1 in the pooled group (P = 0.0001 and 0.046, respectively). In the subset, total (P = 0.001) and pulsatile (P = 0.002) GH secretion, mean GH concentration (P = 0.002), mass of GH secreted per pulse (P = 0.01) and pulse frequency (P = 0.04) were all higher after 12 weeks of CPAP compared with sham. Basal secretion, interpulse regularity, and GH regularity were not different between groups (all P > 0.11).
  
  
  CONCLUSIONS
  Twelve weeks, but not 6 weeks, of CPAP increases IGF-1, with a further increase after 24 weeks. Total and pulsatile GH secretion, secretory burst mass and pulse frequency are also increased by 12 weeks. CPAP improves specific elements of the GH/IGF-1 axis in a time-dependent manner.
  
  
  BACKGROUND
  Australia New Zealand Clinical Trials Network, www.anzctr.org.au, number ACTRN12608000301369.
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Glebe, NSW, Australia.
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Hoyos
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Glebe, NSW, Australia.
authors.forename: Roo
authors.initials: R
authors.lastname: Killick
authors.affiliation: Department of Statistics, University of Virginia, Charlottesville, VA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Keenan
authors.affiliation: Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
authors.affiliation: Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, MN.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.affiliation: NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Glebe, NSW, Australia ; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Los Angeles, CA.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Liu
mesh_terms: D000368:Aged; D001315:Australia; D045422:Continuous Positive Airway Pressure; D004311:Double-Blind Method; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020181:Sleep Apnea, Obstructive / Q000097:blood* / Q000378:metabolism*; D013002:Somatomedins; D013997:Time Factors
chemical_list: C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Continuous positive airway pressure; IGF binding protein; growth hormone; insulin-like growth factor 1; obstructive sleep apnea; pulsatility