title: Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity.
abstract: BACKGROUND
  Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity.
  
  
  OBJECTIVE
  To examine whether sleep apnea and nocturnal hypoxemia predict the severity of insulin resistance, systemic inflammation, and steatohepatitis in severely obese individuals presenting for bariatric surgery.
  
  
  METHODS
  We performed sleep studies and measured fasting blood glucose, serum insulin, C-reactive protein, and liver enzymes in 90 consecutive severely obese individuals, 75 women and 15 men, without concomitant diabetes mellitus or preexistent diagnosis of sleep apnea or liver disease. Liver biopsies (n = 20) were obtained during bariatric surgery.
  
  
  RESULTS
  Obstructive sleep apnea with a respiratory disturbance index greater than 5 events/hour was diagnosed in 81.1% of patients. The median respiratory disturbance index was 15 +/- 29 events/hour and the median oxygen desaturation during apneic events was 4.6 +/- 1.8%. All patients exhibited high serum levels of C-reactive protein, regardless of the severity of apnea, whereas liver enzymes were normal. Oxygen desaturation greater than 4.6% was associated with a 1.5-fold increase in insulin resistance, according to the homeostasis model assessment index. Histopathology data suggested that significant nocturnal desaturation might predispose to hepatic inflammation, hepatocyte ballooning, and liver fibrosis. Fasting blood glucose levels and steatosis scores were not affected by nocturnal hypoxia. There was no relationship between the respiratory disturbance index and insulin resistance or liver histopathology.
  
  
  CONCLUSIONS
  Hypoxic stress of sleep apnea may be implicated in the development of insulin resistance and steatohepatitis in severe obesity.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. vpolots1@jhmi.edu
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
authors.forename: Susheel P
authors.initials: SP
authors.lastname: Patil
authors.forename: Vladimir
authors.initials: V
authors.lastname: Savransky
authors.forename: Alison
authors.initials: A
authors.lastname: Laffan
authors.forename: Shannon
authors.initials: S
authors.lastname: Fonti
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Frame
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Steele
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schweizter
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Clark
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D004797:Enzyme-Linked Immunosorbent Assay; D005234:Fatty Liver / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008297:Male; D008396:Maryland / Q000453:epidemiology; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications* / Q000473:pathology; D011379:Prognosis; D012720:Severity of Illness Index; D012890:Sleep / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin