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Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine; ² Department of Surgery; ³ Division of General Internal Medicine, Department of Medicine; ⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; and ⁵ Department of Pathology, Johns Hopkins University, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Vsevolod Y. Polotsky, M.D., Ph.D., Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: vpolots1{at}jhmi.edu

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.

Key Words: hypoxemia • fatty liver disease • metabolic syndrome • sleep-disordered breathing • liver injury

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Sleep apnea predisposes to metabolic dysfunction and systemic inflammation and may lead to liver injury, but its effect in severe obesity is unknown. What This Study Adds to the Field Nocturnal oxygen desaturation is associated with insulin resistance and may predispose to nonalcoholic fatty liver disease in severe obesity, but does not affect serum C-reactive protein levels.

 

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