+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      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

      , MD a , , MD a , , PhD b , , MD c , , MD a


      metabolic syndrome, sleep apnea, CPAP, leptin

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          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.


          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.


          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.

          Related collections

          Most cited references 52

          • Record: found
          • Abstract: found
          • Article: not found

          Banting lecture 1988. Role of insulin resistance in human disease.

           G M Reaven (1988)
          Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)
            • Record: found
            • Abstract: found
            • Article: not found

            Prevalence of impaired glucose tolerance among children and adolescents with marked obesity.

            Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents. All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose. Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance. Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.
              • Record: found
              • Abstract: found
              • Article: not found

              Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems.

              Objective: To develop and validate questionnaire scales that can be used in research to investigate the presence of childhood SRBDs and prominent symptom complexes, including snoring, daytime sleepiness, and related behavioral disturbances.Background: Obstructive sleep-related breathing disorders (SRBDs) are common but usually undiagnosed among children. Methods to help identify SRBDs without the expense of polysomnography could greatly facilitate clinical and epidemiological research.Methods: Subjects were children aged 2-18 years who had polysomnographically-confirmed SRBDs (n=54) or appointments at either of two general pediatrics clinics (n=108). Parents completed a Pediatric Sleep Questionnaire which contained items under consideration for inclusion in desired scales.Results: Item reduction, based on data from a randomly selected 50% of the subjects (group A), produced a 22-item SRBD score that was strongly associated with diagnosis of an SRBD (P<0.0001) in a logistic regression model that accounted for age and gender. Diagnosis was also strongly associated with subscores for snoring (four items, P<0.0001), sleepiness (four items, P=0.0003), and behavior (six items, P<0.0001) among group A subjects. The scales performed similarly well among group B subjects, and among subjects of different ages and gender. In group A and B subjects, respectively, a selected criterion SRBD score produced a sensitivity of 0.85 and 0.81; a specificity of 0.87 and 0.87; and a correct classification for 86 and 85% of subjects. The scales showed good internal consistency and, in a separate sample (n=21), good test-retest stability.Conclusions: These scales for childhood SRBDs, snoring, sleepiness, and behavior are valid and reliable instruments that can be used to identify SRBDs or associated symptom-constructs in clinical research when polysomnography is not feasible.

                Author and article information

                13 November 2016
                September 2008
                21 November 2016
                : 122
                : 3
                : e634-e642
                [a ]Section of Respiratory Medicine, Yale University School of Medicine, New Haven, Connecticut
                [b ]Yale Center for Clinical Investigation, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut
                [c ]Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut
                Author notes
                Address correspondence to Alia Bazzy-Asaad, MD, Yale University School of Medicine, Department of Pediatrics, Section of Respiratory Medicine, 333 Cedar St, Fitkin 510, New Haven, CT 06520. alia.bazzy-asaad@ 123456yale.edu

                Permissions & Licensing: Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: /site/misc/Permissions.xhtml


                metabolic syndrome, sleep apnea, cpap, leptin


                Comment on this article