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

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.