Published online September 1, 2008
PEDIATRICS Vol. 122 No. 3 September 2008, pp. e634-e642 (doi:10.1542/peds.2008-0154)

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ARTICLE

Sleep-Disordered Breathing in Children With Metabolic Syndrome: The Role of Leptin and Sympathetic Nervous System Activity and the Effect of Continuous Positive Airway Pressure

Neal Nakra, MD^a, Sumit Bhargava, MD^a, James Dzuira, PhD^b, Sonia Caprio, MD^c and Alia Bazzy-Asaad, MD^a

Sections of ^a Respiratory Medicine
^c Endocrinology
^b Yale Center for Clinical Investigation, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut

OBJECTIVE. The purpose of this work was to determine whether, in children with metabolic syndrome and sleep-disordered breathing, metabolic markers separate them from children with metabolic syndrome without sleep-disordered breathing and whether treatment of sleep-disordered breathing with continuous positive airway pressure is associated with an improvement in metabolic derangement.

PATIENTS AND METHODS. Subjects aged 7 to 19 years old with metabolic syndrome and a positive validated sleep questionnaire were recruited. Subjects underwent overnight polysomnography, during which sympathetic nervous system activity was assessed via 8-hourly measurements of norepinephrine and epinephrine, together with leptin. The next morning, a fasting 3-hour oral glucose-tolerance test was performed to calculate whole-body insulin sensitivity. A fasting lipid panel interleukin 6, adiponectin, and C-reactive protein levels were also measured. Children with sleep-disordered breathing were placed on continuous positive airway pressure for 3 months and studied again. Sleep-disordered breathing and no sleep-disordered breathing groups were compared by using Fisher's exact test and t test for independent samples with analysis of covariance to adjust for age and BMI.

RESULTS. Of 34 children studied, 25 had sleep-disordered breathing (apnea-hypopnea index: >1.5). Mean hourly norepinephrine and leptin levels were higher in the group with sleep-disordered breathing compared with the group without sleep-disordered breathing (P < .005), with no difference in whole-body insulin sensitivity. Eleven subjects with sleep-disordered breathing completed 3 months of nightly continuous positive airway pressure treatment. In the follow-up study, mean hourly leptin levels were significantly lower than in the initial study, with no change in BMI z score or other measurements.

CONCLUSION. Our findings support the hypothesis that sleep-disordered breathing in children with metabolic syndrome is associated with increased sympathetic nervous system activity and leptin levels but not worsening of insulin resistance. Treatment of sleep-disordered breathing with continuous positive airway pressure led to a significant decrease in leptin levels.

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Key Words: metabolic syndrome • sleep apnea • CPAP • leptin

Abbreviations: SDB—sleep-disordered breathing • SNSA—sympathetic nervous system activity • OSA—obstructive sleep apnea • HDL—high-density lipoprotein • OGTT—oral glucose-tolerance test • IL—interleukin • CRP—C-reactive protein • AHI—apnea-hypopnea index • CPAP—continuous positive airway pressure • SPO₂: pulse oxygen saturation

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Accepted May 20, 2008.

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