title: Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance.
abstract: Obstructive sleep apnoea (OSA) is a very prevalent disorder particularly amongst middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness'. In 1997, we first reported that the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor-alpha (TNF alpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNF alpha plasma levels and the body mass index (BMI). In subsequent studies, we showed that IL-6, TNF alpha, leptin and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnoea. The association of OSA with insulin resistance and diabetes type 2 has been confirmed since then in several epidemiological and clinical studies. Furthermore, our findings that women with polycystic ovary syndrome (PCOS, a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness support the pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnoea and sleepiness may be manifestations of a serious metabolic disorder, namely the Metabolic or Visceral Obesity Syndrome, include: obesity without sleep apnoea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity and age; and increased prevalence of sleep apnoea in postmenopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA. In conclusion, accumulating evidence provides support to our model of the bi-directional, feedforward, pernicious association between sleep apnoea, sleepiness, inflammation and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
authors.affiliation: Department of Psychiatry, Penn State College of Medicine, Hershey, PA 17033, USA. axv3@psu.edu
authors.forename: A N
authors.initials: AN
authors.lastname: Vgontzas
authors.forename: E O
authors.initials: EO
authors.lastname: Bixler
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016207:Cytokines / Q000502:physiology; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008593:Menopause / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism; D012891:Sleep Apnea Syndromes / Q000378:metabolism*; D014781:Viscera / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D016207:Cytokines