The Role of Obstructive Sleep Apnea in Children With Fatty Liver Disease

The Role of Obstructive Sleep Apnea in the Pathogenesis of Hepatic Steatosis in Obese Children and Adolescents

The purpose of this study is to examine whether CPAP therapy can reduce or eliminate hepatic fat accumulation in obese children and adolescents.

NAFLD is emerging as one of the most common complications of childhood obesity. It is associated with and predicts the metabolic syndrome, independent of overall obesity. Recently, studies in obese adolescents have demonstrated that increased ALT levels are associated with deterioration in insulin sensitivity and glucose tolerance, as well as with increasing FFA and triglyceride levels. Further studies showed that the prevalence of metabolic syndrome and prediabetes increases with the increases in hepatic fat content in a cohort of obese adolescents. Moreover, the investigators found that the fatty liver is associated with a pronounced dyslipidemic profile characterized by large VLDL, small dense LDL, and decreased large HDL concentrations. Fatty liver, independent of visceral and intramyocellular lipid content plays a central role in the impairment of liver, muscle and adipose insulin sensitivity in obese adolescents. Thus, fatty liver disease may be the hepatic component of the metabolic syndrome. The synthesis of triglycerides in the liver is nutritionally regulated, and its formation from simple carbohydrates requires multiple metabolic pathways, including glycolysis and pyruvate oxidation to generate acetyl-CoA for fatty acid synthesis, NADPH generation to supply the reductive power, packaging of fatty acids into a glycerophosphate backbone, and finally, lipoprotein packaging to export triglycerides. Recent studies have shown an association between fatty liver and obstructive sleep apnea (OSA), a condition that has been estimated to affect up to 27% of obese children. In particular, OSA has been associated with the ALT levels and with the degree of steatohepatitis. Despite those evidences and the importance of NAFLD in the development of metabolic diseases, the information concerning the association between fatty liver and OSA in obese children and adolescents is quite sparse and in particular is unclear whether OSA itself can cause NAFLD or the two conditions just coexist as obesity complications. In this study the investigators will test the hypothesis that OSA is one of the determinants of hepatic fat accumulation. To prove the investigators hypothesis the investigators will select a group of individuals with NAFLD and OSA, who will undergo a weight maintenance diet and Continuous Positive Airway Pressure (CPAP) for 12 weeks. CPAP is FDA approved and represents the leading therapy for obstructive sleep apnea in children over age 7 and 40 lbs. To evaluate the effect of the CPAP on the intra hepatic fat accumulation the investigators will evaluate hepatic fat content with MRI at baseline and after the intervention.

Continuous positive airway pressure is a commonly prescribed therapy for obstructive sleep apnea which is recommended for the treatment of obstructive sleep apnea in children and adults.

Continuous positive airway pressure is a commonly prescribed therapy for obstructive sleep apnea which is recommended for the treatment of obstructive sleep apnea in children and adults.

2 hour glucose measured by an oral glucose tolerance test done at baseline and 12 weeks. Data are presented as mg/dl.

Inclusion Criteria: Sleep Apnea as diagnosed by clinical sleep study (Apnea Hypopnea index greater than 1) Evidence of NAFLD as diagnosed by screening MRI (hepatic fat fraction ≥5.5%) Obese child/adolescent between 9-21 years old Compliance with using C-pap as instructed Exclusion Criteria: Medications or know disease known to alter glucose or insulin metabolism such as oral steroids, or certain psychiatric medications, such as Xeleca, Lithium and Paxil. Type 2 Diabetes Mellitus Medications for chronic anti-inflammatory effects Consumption of alcohol