TY - JOUR
T1 - Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity
AU - Polotsky, Vsevolod Y.
AU - Patil, Susheel P.
AU - Savransky, Vladimir
AU - Laffan, Alison
AU - Fonti, Shannon
AU - Frame, Leigh A.
AU - Steele, Kimberly E.
AU - Schweizter, Michael A.
AU - Clark, Jeanne M.
AU - Torbenson, Michael S.
AU - Schwartz, Alan R.
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Rationale: 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. Objectives: 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. Measurements and Main 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.
AB - Rationale: 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. Objectives: 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. Measurements and Main 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.
KW - Fatty liver disease
KW - Hypoxemia
KW - Liver injury
KW - Metabolic syndrome
KW - Sleep- Disordered breathing
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U2 - 10.1164/rccm.200804-608OC
DO - 10.1164/rccm.200804-608OC
M3 - Article
C2 - 18990675
AN - SCOPUS:61449212091
SN - 1073-449X
VL - 179
SP - 228
EP - 234
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 3
ER -