Camilla M Hoyos1, Roo Killick1, Daniel M Keenan2, Robert C Baxter3, Johannes D Veldhuis4, Peter Y Liu5. 1. NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Glebe, NSW, Australia. 2. Department of Statistics, University of Virginia, Charlottesville, VA. 3. Kolling Institute of Medical Research, University of Sydney, St Leonards, Australia. 4. Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science Center, Mayo Clinic, Rochester, MN. 5. 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.
Abstract
STUDY OBJECTIVES: 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. DESIGN: A randomized, double-blind, sham-controlled, parallel group study. PARTICIPANTS: Sixty-five middle-aged men with moderate to severe obstructive sleep apnea. INTERVENTION: Active (n = 34) or sham (n = 31) CPAP for 12 weeks, followed by 12 weeks of active CPAP (n = 65). MEASUREMENTS AND 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. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Network, www.anzctr.org.au, number ACTRN12608000301369.
RCT Entities:
STUDY OBJECTIVES: 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. DESIGN: A randomized, double-blind, sham-controlled, parallel group study. PARTICIPANTS: Sixty-five middle-aged men with moderate to severe obstructive sleep apnea. INTERVENTION: Active (n = 34) or sham (n = 31) CPAP for 12 weeks, followed by 12 weeks of active CPAP (n = 65). MEASUREMENTS AND 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. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Network, www.anzctr.org.au, number ACTRN12608000301369.
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