Abstract and Introduction
Abstract
Objective: Obstructive sleep apnoea (OSA) is reported to have effects on a number of hormone systems including the hypothalamo-pituitary axis. We aimed to determine the impact of OSA severity on insulin-like growth factor-I (IGF-I) levels.
Design and Methods: This is a prospective cohort study performed between November 2014 and May 2017. IGF-I was measured on serum samples, and data were collected on demographics, BMI and parameters of OSA.
Results: 611 participants were recruited (202 female, 53.5 ± 12.5 years; mean BMI 36.2 ± 8.0 kg/m2). 26.2% had mild OSA; 27.3%, moderate OSA; and 44.5%, severe OSA. 15.2% of IGF-I values were below the age-related reference range. Increasing BMI correlated with greater AHI (r = .28, p < .001), ODI (r = .30, p < .001), severity of OSA (r = .17, p < .001), duration with oxygen saturation (SaO2) <90% (r = .29, p = .001) and reduced median SaO2 levels (r = .19, p < .001). IGF-I levels correlated negatively with age (r = −.13, p = .001), BMI (r = −.16, p < .001), diabetes (r = −.108, p = .009), AHI (r = -0.10, p = .043) and severity of OSA (r = −.10, p = .013). No association of IGF-I was observed with ODI, median SaO2 levels or duration of SaO2 < 90%. Regression analyses were used to examine determinants of IGF-I, all of which contained the independent variables of age, gender and BMI. All models showed IGF-I to be predicted by age and BMI (p < .05); however, none of the parameters of OSA were significant within these models.
Conclusion: Insulin-like growth factor-I levels in OSA are dependent on age and BMI; however, no additional effect of any OSA parameter was observed, supporting the hypothesis that OSA effects on IGF-I are indirect through concomitant body composition and metabolic parameters.
Introduction
Obstructive sleep apnoea (OSA) syndrome is characterized by cyclic intermittent reduction (hypopnoea) or absence of airflow (apnoea) which occurs as a result of collapse or partial collapse of the upper airway during sleep.[1] The physiological consequences are marked changes in intrathoracic pressure, sleep fragmentation, intermittent hypoxaemia and nocturnal arousal,[1,2] in turn leading to reduced duration of slow-wave sleep (SWS) and rapid eye movement (REM) sleep, with increased light sleep. In the USA, 26% of individuals aged 30–70 years experience at least mild OSA, with moderate-to-severe OSA present in 10% of the population during the time period 2007–2010.[3] The prevalence of OSA is greater in males[3,4] and increases dramatically with increasing body mass and age.[3,4]
On a social level, OSA is a significant contributor to excessive daytime sleepiness, impaired quality of life, under performance at work, higher rates of disability pensions and road traffic collisions.[5,6] Importantly, OSA is also associated with significant adverse health outcomes, in particular an increased morbidity and mortality[7–9] related in part to increases in coronary heart disease and heart failure.[8–10] Known contributors to premature vascular disease include systemic hypertension, insulin resistance, hyperlipidaemia and metabolic syndrome which occur at a greater prevalence in patients with OSA than in gender and BMI-matched subjects.[2,11,12]
Additionally, OSA is purported to have effects on a number of hormone systems including catecholamines and the hypothalamo-pituitary axes.[13–15] Episodes of sleep fragmentation with arousal are hypothesized to increase activation of the sympathetic nervous system and thereby nocturnal catecholamine release.[11] Growth hormone (GH) secretion is closely related to the stages of sleep. GH is released in discreet pulses with two thirds of GH release occurring within the first few hours of sleep, initiation of pulses being related to phases of SWS.[16] Disturbance and reduction of time in SWS in patients with OSA would therefore be expected to disrupt nocturnal GH secretion. GH acts directly on many tissues; however, many of the actions of GH occur through increases in the level of the second messenger, insulin-like growth factor-I (IGF-I). The majority of circulating IGF-I is derived from the liver and more than 99% is bound to IGF-1 binding proteins, resulting in longer half-life and stable serum levels.[17] The synergistic actions of GH with IGF-1 are vital for skeletal growth in children and maintaining structure and normal metabolism in adults.
A number of studies have documented GH secretion and IGF-I levels to be abrogated in OSA.[18–20] Circulating IGF-I levels are influenced by a number of factors including age, nutritional status, and thyroid, renal and hepatic function. Studies of IGF-I levels in patients with OSA have often been small and confounded by the significant effects of age and obesity on the GH-IGF-I axis.[18,19] We have therefore examined IGF-I levels in a large cohort of patients with OSA allowing us to stratify the cohort for detailed analysis of the effects of OSA on IGF-I levels.
Clin Endocrinol. 2021;94(3):434-442. © 2021 Blackwell Publishing
