Sleep Apnea and Metabolic and Cardiovascular Complications

Abstract

Obesity is reaching epidemic proportions in adults and its prevalence is rising dramatically in children. Obesity, especially central obesity, leads to insulin resistance and type 2 diabetes mellitus, affecting more than 100 million people worldwide. Central obesity is also a major risk factor for sleep apnea, which affects 2–4% of adults in the United States, and has prevalence in excess of 50% in obese, otherwise healthy, males. Thus, both metabolic dysfunction and sleep apnea (SA) are adverse outcomes of obesity and act as important intermediates in the path to cardiovascular morbidity and mortality. The fact that SA and diabetes frequently co-exist in obese individuals has received growing attention. The overwhelming majority of large community and clinic-based studies report a positive association between SA and one or more parameters of metabolic dysfunction, independent of obesity. Treatment of SA with nasal continuous positive airway pressure can lead to improvements in insulin sensitivity, in the absence of any change in body weight, and animal models of SA exhibit reduced insulin sensitivity suggesting that a cause and effect relationship exists between sleep apnea and insulin resistance. Sleep apnea is characterized by recurrent collapse of the upper airway during sleep leading to periods of intermittent hypoxia and sleep fragmentation. The stimulus of intermittent hypoxia is known to activate multiple physiologic systems including sympathetic nerve activity (SNA), the hypothalamic-pituitary-adrenal axis, insulin counter-regulatory hormones, a stress/pro-inflammatory state, and generation of reactive oxygen species. All of these activated pathways can contribute to the development of insulin resistance and putatively act as intermediates in the pathway leading from sleep apnea to cardiovascular morbidity and mortality.