Sleep apnea and daytime sleepiness and fatigue: Relation to visceral obesity, insulin resistance, and hypercytokinemia

Sleep apnea and associated daytime sleepiness and fatigue are common manife stations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea rem ains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previous ly reported changes of plasma cytokine (tumor necrosis factor-alpha and int erleukin-6) and leptin levels independently of obesity? 2) Among obese pati ents, is it generalized or visceral obesity that predisposes to sleep apnea ? 3) Is apnea a factor independent from obesity in the development of insul in resistance? Obese middle-aged men with sleep apnea were first compared w ith nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecu tive nights. We obtained simultaneous indexes of sleep, sleep stages, and s leep apnea, including apnea/hypopnea index and percent minimum oxygen satur ation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lea n men, who had the lowest values. Because these findings suggested that sle ep apneics might have a higher degree of insulin resistance than the BMT-ma tched controls, we studied groups of sleep-apneic obese and age- and BMI-ma tched nonapneic controls in whom we obtained computed tomographic scan meas ures of total, sc, and visceral abdominal fat, and additional biochemical i ndexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fa t compared to obese controls (<0.05) and indexes of sleep disordered breath ing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic co ntrols. We conclude that there is a strong independent association among sl eep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition.