Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity

Vsevolod Polotsky, Susheel Patil, Vladimir Savransky, Alison Laffan, Shannon Fonti, Leigh A. Frame, Kimberley Steele, Michael A. Schweizter, Jeanne Clark, Michael S. Torbenson, Alan R Schwartz

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)228-234
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume179
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Morbid Obesity
Obstructive Sleep Apnea
Fatty Liver
Insulin Resistance
Liver
Sleep Apnea Syndromes
Bariatric Surgery
Apnea
C-Reactive Protein
Blood Glucose
Fasting
Oxygen
Inflammation
Enzymes
Serum
Liver Cirrhosis
Liver Diseases
Hepatocytes
Diabetes Mellitus
Sleep

Keywords

  • Fatty liver disease
  • Hypoxemia
  • Liver injury
  • Metabolic syndrome
  • Sleep- Disordered breathing

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. / Polotsky, Vsevolod; Patil, Susheel; Savransky, Vladimir; Laffan, Alison; Fonti, Shannon; Frame, Leigh A.; Steele, Kimberley; Schweizter, Michael A.; Clark, Jeanne; Torbenson, Michael S.; Schwartz, Alan R.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 3, 01.02.2009, p. 228-234.

Research output: Contribution to journalArticle

Polotsky, Vsevolod ; Patil, Susheel ; Savransky, Vladimir ; Laffan, Alison ; Fonti, Shannon ; Frame, Leigh A. ; Steele, Kimberley ; Schweizter, Michael A. ; Clark, Jeanne ; Torbenson, Michael S. ; Schwartz, Alan R. / Obstructive sleep apnea, insulin resistance, and steatohepatitis in severe obesity. In: American Journal of Respiratory and Critical Care Medicine. 2009 ; Vol. 179, No. 3. pp. 228-234.
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AU - Polotsky, Vsevolod

AU - Patil, Susheel

AU - Savransky, Vladimir

AU - Laffan, Alison

AU - Fonti, Shannon

AU - Frame, Leigh A.

AU - Steele, Kimberley

AU - Schweizter, Michael A.

AU - Clark, Jeanne

AU - Torbenson, Michael S.

AU - Schwartz, Alan R

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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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