The relationship between sleep-disordered breathing, blood pressure, and urinary cortisol and catecholamines in children.

STUDY OBJECTIVES: Hypertension is a complication of obstructive sleep apnea (OSA) syndrome in adults. A correlation between OSA syndrome and elevated blood pressure (BP) is suggested in children, but its pathogenesis remains unclear. Our aim was to study the effects of sleep and sleep apnea on BP and sympathetic nervous system activation as measured by serum cortisol and urinary catecholamines. We hypothesized that children with OSA syndrome would have higher BP, urinary catecholamines, and cortisol compared with controls. METHODS: We measured BP during polysomnography in 78 children with suspected sleep-disordered breathing and 18 nonsnoring controls. BP was measured during wakefulness and every 30-60 minutes throughout the night. All participants had 24-hour urinary catecholamine and free cortisol collections 48 hours before polysomnography. RESULTS: BP varied with sleep stage; it was highest during wakefulness and N1 and lowest during non-rapid eye movement stage 3. Children classified as high apnea-hypopnea index (AHI) snorers (AHI >5 events/h) had a greater prevalence of systolic hypertension (57%) than low-AHI snorers (22%) and nonsnoring controls (22%; P = .04). The high-AHI snorers also had higher diastolic BP (P < .02) as well as blunted nocturnal diastolic BP changes during sleep (P = .02) compared with low-AHI snorers (AHI <5 events/h). Twenty-hour urinary free cortisol and 24-hour urinary catecholamines were not associated with BP. CONCLUSIONS: BP in children varies with sleep stage. OSA is associated with systolic hypertension, higher BP during rapid eye movement sleep, as well as elevation of diastolic BP and blunted BP changes with sleep.

Insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to cardiovascular disease biomarkers in obese adolescents.

CONTEXT: Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 have been linked to cardiovascular disease (CVD) risk and pathophysiology in adults, but there are limited data in youth. OBJECTIVE: The aim of the study was to examine the relationship between IGF and IGFBP-1 with traditional and non-traditional CVD risk factors including inflammatory markers and body composition in an obese pediatric cohort. DESIGN: A cross-sectional study. SETTING: The study was carried out at a university children's hospital. SUBJECTS: Sixty-one obese non-diabetic adolescents. OUTCOMES: Fasting IGF-I, IGFBP-1, lipoprotein profiles, high-sensitivity C-reactive protein (hsCRP), and total adiponectin as well as insulin sensitivity measures, blood pressure (BP), and anthropometrics. RESULTS: IGFBP-1 was negatively associated with insulin sensitivity measures, body mass index (BMI), and diastolic BP in males. IGF-I was negatively associated with hsCRP (r = -0.479, p < 0.0005), and IGFBP-1 was positively associated with adiponectin (r = 0.545, p < 0.0005). The IGF-I/CRP and IGFBP-1/adiponectin associations remained significant when controlling for both BMI and insulin sensitivity index (SI ). Both IGF-I and IGFBP-1 were negatively associated with waist circumference (r = -0.327 and r = -0.275, respectively) and sagittal abdominal diameter (r = -0.333 and r = -0.371, respectively), while IGFBP-1 was negatively associated with fat mass (r = -0.347, p = 0.01) as well as neck circumference and fat-free mass in males. Controlling for BMI z-score and SI , IGFBP-1 remained negatively associated with diastolic blood pressure (r = 0.706, p = 0.001 and neck circumference (r = -0.548, p = 0.15) in males. CONCLUSIONS: IGF-I and IGFBP-1 associate with CVD risk markers and may add to clinical assessments of cardiometabolic dysfunction in youth.

High Risk of Diabetes and Neurobehavioral Deficits in Individuals With Surgically Treated Hyperinsulinism.

CONTEXT: Children with the most common and severe type of congenital hyperinsulinism (HI) frequently require pancreatectomy to control the hypoglycemia. Pancreatectomy increases the risk for diabetes, whereas recurrent hypoglycemia places children at risk of neurocognitive dysfunction. The prevalence of these complications is not well defined. OBJECTIVE: The objective was to determine the prevalence of diabetes and neurobehavioral deficits in surgically treated HI. DESIGN: This was designed as a cross-sectional study of individuals who underwent pancreatectomy for HI between 1960 and 2008. OUTCOMES: Diabetes outcomes were assessed through patient interview and medical record review. Neurobehavioral outcomes were assessed through the Adaptive Behavior Assessment System, 2nd edition (ABAS-II), and the Child Behavior Checklist (CBCL). RESULTS: A total of 121 subjects were enrolled in the study at a median age of 8.9 years (range, 3.5-50.7 y). Thirty-six percent (44 of 121) of subjects had diabetes. Nine subjects developed diabetes immediately after pancreatectomy. Of the remaining 35 subjects who developed diabetes, the median age at diabetes diagnosis was 7.7 years (range, 8 mo to 43 y). In subjects with diabetes, the median hemoglobin A1c was 7.4% (range, 6.5-12.6%), and 38 (86%) subjects required insulin. Subjects with diabetes had a greater percentage of pancreatectomy than subjects without diabetes (95% [range, 65-98] vs 65% [1-98]). Neurobehavioral abnormalities were reported in 58 (48%) subjects. Nineteen (28%) subjects had abnormal ABAS-II scores, and 10 (16%) subjects had abnormal CBCL scores. CONCLUSIONS: Children, who undergo near-total pancreatectomy are at high risk of developing diabetes. Neurobehavioral deficits are common, and developmental assessment is essential for children with HI.

Respiratory cortical processing to inspiratory resistances during wakefulness in children with the obstructive sleep apnea syndrome.

Children with the obstructive sleep apnea syndrome (OSAS) have impaired respiratory afferent cortical processing during sleep that persists after treatment of OSAS. However, it is unknown whether this impairment is present during wakefulness and, if so, whether it improves after OSAS treatment. We hypothesized that children with OSAS, during wakefulness, have abnormal cortical processing of respiratory stimuli manifested by blunted respiratory-related evoked potentials (RREP) and that this resolves after OSAS treatment. We measured RREP during wakefulness in 26 controls and 21 children with OSAS before and after treatment. Thirteen participants with OSAS repeated testing 3-6 mo after adenotonsillectomy. RREP were elicited by interruption of inspiration by total occlusion and 30 and 20 cmH2O/l per s resistances. Nf at Fz latency elicited by occlusion was longer in children with OSAS at baseline compared with controls (78.8 ± 24.8 vs. 63.9 ± 19.7 ms, P = 0.05). All other peak amplitudes and latencies were similar between the two groups. After OSAS treatment, Nf at Fz latency elicited by 30 cmH2O/l per s decreased significantly (before, 88 ± 26 vs. after, 71 ± 25 ms, P = 0.02), as did that elicited by 20 cmH2O/l per s (85 ± 27 vs. 72 ± 24 ms, P = 0.004). The amplitude of N1 at Cz elicited by occlusion increased from -3.4 ± 5.6 to -7.4 ± 3 µV (P = 0.049) after treatment. We concluded that children with OSAS have partial delay of respiratory afferent cortical processing during wakefulness that improves after treatment.

Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea.

STUDY OBJECTIVES: Children and adults with obstructive sleep apnea syndrome (OSAS) exhibit neurobehavioral abnormalities, but few studies have evaluated the transitional stage of adolescence. Obesity is also associated with neurobehavioral abnormalities, and many patients with OSAS are obese. However, the confounding effect of obesity on neurobehavioral abnormalities in adolescents with OSAS has not been evaluated. We hypothesized that obese adolescents with OSAS would exhibit more neurobehavioral abnormalities than obese and lean adolescents without OSAS. DESIGN: Cross-sectional, case control. SETTING: Sleep Center and community. PARTICIPANTS: Obese adolescents with OSAS compared to (1) nonsnoring, obese controls without OSAS, and (2) nonobese, nonsnoring controls. INTERVENTIONS: Neurobehavioral evaluation. MEASUREMENTS AND RESULTS: Obese adolescents with OSAS had significantly worse executive function and attention compared to both obese (P < 0.001) and lean (P < 0.001) controls, and more depression (P = 0.004) and externalizing symptoms than lean controls (P = 0.008). A higher percentage of participants in the OSAS group scored in the clinically abnormal range on executive functioning, attention, sleepiness, and behavioral functioning than lean controls. Mediation analyses indicated that level of sleep apnea significantly mediated the effect of body mass on executive functioning, attention, and behavior. CONCLUSIONS: Obese adolescents with OSAS show impaired executive and behavioral function compared to obese and lean controls, and are more likely to score in the clinically abnormal range on measures of neurobehavioral functioning. These results are especially concerning given that the frontal lobe is still developing during this critical age period. We speculate that untreated OSAS during adolescence may lead to significant neurobehavioral deficits in adulthood.

Predictors of perioperative complications in higher risk children after adenotonsillectomy for obstructive sleep apnea: a prospective study.

OBJECTIVE: Retrospective studies have limitations in predicting perioperative risk following adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS). Few prospective studies exist. We hypothesized that demographic and polysomnographic (PSG) variables would predict respiratory and general perioperative complications. STUDY DESIGN: Prospective, observational cohort study. SETTING: Pediatric tertiary center. SUBJECTS AND METHODS: Consecutive children undergoing adenotonsillectomy for OSAS within 12 months of PSG were evaluated for complications occurring within 2 weeks of surgery. RESULTS: There were 329 subjects, with 27% <3 years old, 24% obese, 16% preterm, and 29% with comorbidities. In this higher risk population, 28% had respiratory complications (major and/or minor), and 33% had nonrespiratory complications. Significant associations were found between PSG parameters and respiratory complications as follows: apnea hypopnea index (rank-biserial correlation coefficient [r] = 0.174, P = .017), SpO2 nadir (r = -0.332, P < .0005), sleep time with SpO2 <90% (r = 0.298, P < .0005), peak end-tidal CO2 (r = 0.354, P < .0005), and sleep time with end-tidal CO2 >50 mm Hg (r = 0.199, P = .006). Associations were also found between respiratory complications and age <3 years (r = -0.174, P = .003) or black race (r = 0.123, P = .039). No significant associations existed between PSG parameters and nonrespiratory complications. A model using age <3 years, SpO2 nadir, and peak CO2 predicted respiratory complications better than the American Academy of Pediatrics or American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines but was imperfect (area under the curve = 0.72). CONCLUSION: Thus, PSG predicted perioperative respiratory, but not nonrespiratory, complications in children with OSAS. Age <3 years or black race are high-risk factors. Present guidelines have limitations in determining the need for postoperative admission.

Prevalence of periodic limb movements during sleep in normal children.

STUDY OBJECTIVES: Although the American Academy of Sleep Medicine (AASM) mandates that periodic limb movements during sleep (PLMS) be scored on every polysomnogram, and considers a periodic limb movement index (PLMI) > 5/h abnormal in children, there is a lack of community-derived data regarding the prevalence of PLMS in children, and no data to support this cutoff value. Therefore, the aim of this study was to determine the prevalence of PLMS in a sample of normal children. DESIGN: Retrospective study. PARTICIPANTS: 195 healthy, non-snoring children aged 5-17 years, recruited from the community, who underwent polysomnography for research purposes. METHODS: PLMS were scored using the AASM 2007 criteria. MEASUREMENTS AND RESULTS: The group age (median [IQR]) was 12.9 [10-15] years, and 58% were male. Sleep architecture was normal, and the obstructive apnea hypopnea index was 0.1 [0-0.3]/h. The median PLMI was 0/h, ranging from 0 to 35.5/h. Fifteen (7.7%) subjects had a PLMI > 5/h, and only 3 (1.5%) met the adult pathologic criterion of more than 15/h. Use of the 95th percentile PLMI cutoff of 7.2/h produced little difference in categorization between groups. Children with a PLMI > 5/h had a higher arousal index than those with a lower PLMI (11.6 [8.8-14.6] vs 8.1 [6.1-9.9]/h, respectively, P = 0.003). CONCLUSIONS: This study provides normative data to the field and supports the clinical periodic limb movement index cutoff of > 5/h based on both prevalence and the correlate of increased sleep fragmentation. Periodic limb movements during sleep are infrequent in normal children recruited from the community. CITATION: Marcus CL, Traylor J, Gallagher PR, Brooks LJ, Huang J, Koren D, Katz L, Mason TB, Tapia IE. Prevalence of periodic limb movements during sleep in normal children.

Utility of screening for obstructive sleep apnea syndrome in children with craniofacial disorders.

BACKGROUND: Children with craniofacial disorders are at increased risk for obstructive sleep apnea syndrome. Methods for diagnosing obstructive sleep apnea syndrome in this population remain controversial. Sleep studies are the criterion standard but are impractical for all patients. The utility of obstructive sleep apnea syndrome questionnaires such as the Pediatric Sleep Questionnaire is unknown in children with craniofacial disorders. The authors hypothesized that the Pediatric Sleep Questionnaire would be a sensitive tool for detecting obstructive sleep apnea syndrome in children with craniofacial abnormalities. METHODS: A retrospective review of consecutive children with diagnosed craniofacial disorders who both completed the Pediatric Sleep Questionnaire and underwent polysomnography was performed. Demographics, Pediatric Sleep Questionnaire score, and polysomnographic data were recorded. Statistical analysis included calculation of sensitivity, specificity, positive predictive value, and negative predictive value for the Pediatric Sleep Questionnaire. RESULTS: Eighty-three children aged 2 to 18 years were included in the study. Of these, 44 (53.0 percent) screened positive on the Pediatric Sleep Questionnaire and 23 (27.7 percent) had polysomnographic evidence of obstructive sleep apnea syndrome, but the sensitivity of the Pediatric Sleep Questionnaire for detecting obstructive sleep apnea syndrome in this sample was only 0.57 and the specificity was 0.48. Positive predictive value and negative predictive value were 0.30 and 0.74, respectively. The correlation between the apnea hypopnea index and Pediatric Sleep Questionnaire score was 0.152 (p = 0.17). CONCLUSIONS: A substantial portion of craniofacial patients referred for polysomnography was found to have obstructive sleep apnea syndrome. However, the Pediatric Sleep Questionnaire is not a good screening tool for obstructive sleep apnea syndrome in children with craniofacial conditions. More research is needed to determine which patients with craniofacial disorders should be evaluated for obstructive sleep apnea syndrome by polysomnography or other means. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Alternative therapies for childhood obstructive sleep apnea syndrome (OSAS) are needed as OSAS may persist despite adenotonsillectomy, and continuous positive airway pressure (CPAP) adherence is low. Nasal expiratory positive airway pressure (NEPAP) devices have not been studied in children. We hypothesized that NEPAP would result in polysomnographic improvement. Further, we aimed to determine NEPAP adherence, effects on sleepiness, behavior, and quality of life. METHODS: A randomized, double-blind, placebo-controlled, crossover pilot study was performed. CPAP candidates, 8-16 years old, underwent NEPAP and placebo polysomnograms. Subjects with ≥ 50% reduction in the apnea hypopnea index (AHI) from placebo to NEPAP night or AHI < 5/h on NEPAP night wore NEPAP at home for 30 days. Adherence was assessed by daily phone calls/emails and collecting used devices. RESULTS: Fourteen subjects (age 13.4 ± 1.9 years, BMI z-scores 2.2 ± 1 [mean ± SD]) were studied. There was significant improvement in the obstructive apnea index with NEPAP vs. placebo: 0.6 (0-21.1)/h vs. 4.2 (0-41.9)/h (median [range], p = 0.010) and trends for improvement in other polysomnographic parameters. However, responses were variable, with 3 subjects not improving and 2 worsening. Older children and those with less hypercapnia had a better response. Eight subjects were sent home with devices; one was lost to follow-up, and adherence in the remainder was 83% of nights; these subjects had a significant improvement in sleepiness and quality of life. CONCLUSIONS: NEPAP devices are a potential alternative therapy for OSAS in a small subset of children. Due to variability in individual responses, efficacy of NEPAP should be evaluated with polysomnography. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT01768065.

Anthropometric measures of abdominal adiposity for the identification of cardiometabolic risk factors in adolescents.

Sagittal abdominal diameter (SAD) was obtained in 65 adolescents referred for assessment of cardiometabolic risk. We found that SAD was associated with cardiometabolic risk factors independent of BMI in males, but that SAD was not superior to BMI or other measures of abdominal adiposity for the detection of metabolic syndrome.

Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases.

CONTEXT: Congenital hyperinsulinism (HI) occurs in two distinct histologic forms: diffuse and focal. Distinguishing between them is essential because a pancreatectomy is curative for focal HI and palliative for diffuse HI. OBJECTIVE: The purpose of this study was to compare the presentations, treatment, and outcomes of diffuse and focal HI. DESIGN: A retrospective chart review of children who underwent pancreatectomy for hyperinsulinism from December 2004 through September 2012 was conducted. RESULTS: Based on pancreatic histology, 223 children were classified into 3 groups: diffuse (n = 97, 44%), focal (n = 114, 51%), and other (n = 12, 5%). Children with diffuse vs focal HI had significantly different mean gestational ages (38 vs 39 weeks, P < .0005) and birth weights (3963 vs 3717 g P = .012). Children with focal HI presented at an older age (0.3 vs 0 months, P < .0005) and more frequently with seizures (50 vs 25%, P < .0005). Children with diffuse HI had higher insulin levels during hypoglycemia (31.8 vs 12 µU/mL, P < .0005) and required higher glucose infusion rates (19.2 vs 16.1 mg/kg/min, P = .002). Children with diffuse HI had a median percent pancreactectomy of 98%, and postoperatively 41% required treatment for continued hypoglycemia. Children with focal HI had a median percent pancreatectomy rate of 27%, and 94% required no treatment after surgery. CONCLUSIONS: Focal and diffuse HI present unique challenges, but the clinical differences between the 2 are subtle. Children with focal HI are at higher risk of delayed diagnosis and hypoglycemic seizures, but most are cured with surgery. In contrast, children with diffuse disease may be identified earlier, but face ongoing blood glucose abnormalities.

Respiratory and auditory cortical processing in children with obstructive sleep apnea syndrome.

RATIONALE: Children with obstructive sleep apnea syndrome (OSAS) have impaired cortical processing of respiratory afferent stimuli, manifested by blunted sleep respiratory-related evoked potentials (RREP). However, whether this impairment is limited to respiratory stimuli, or reversible after successful treatment, is unknown. We hypothesized that, during sleep, children with OSAS have (1) abnormal RREP, (2) normal cortical processing of nonrespiratory stimuli, and (3) persistence of abnormal RREP after treatment. OBJECTIVES: To measure sleep RREP and auditory evoked potentials in normal control subjects and children with OSAS before and after treatment. METHODS: Twenty-four children with OSAS and 24 control subjects were tested during N3 sleep. Thirteen children with OSAS repeated testing 4-6 months after adenotonsillectomy. MEASUREMENTS AND MAIN RESULTS: RREP were blunted in OSAS compared with control subjects (N350 at Cz -27 ± 15.5 vs. -47.4 ± 28.5 µV; P = 0.019), and did not improve after OSAS treatment (N350 at Cz pretreatment -25.1 ± 7.4 vs. -29.8 ± 8.1 post-treatment). Auditory evoked potentials were similar in OSAS and control subjects at baseline (N350 at Cz -58 ± 33.1 vs. -66 ± 31.1 µV), and did not change after treatment (N350 at Cz -67.5 ± 36.8 vs. -65.5 ± 20.3). CONCLUSIONS: Children with OSAS have persistent primary or irreversible respiratory afferent cortical processing deficits during sleep that could put them at risk of OSAS recurrence. OSAS does not seem to affect the cortical processing of nonrespiratory (auditory) afferent stimuli during sleep.

A Pilot Study of Fluorodeoxyglucose Positron Emission Tomography Findings in Patients with Phenylketonuria before and during Sapropterin Supplementation.

BACKGROUND AND PURPOSE: PET scanning with fluorodeoxyglucose (FDG-PET) is a non-invasive method that measures regional glucose metabolic rate. Phenylalanine (Phe) and its metabolites appear to impair several aspects of brain energy metabolism. 1) To evaluate brain glucose metabolism with FDG-PET imaging in phenylketonuria (PKU) patients before and 4 months after sapropterin therapy; 2) to evaluate neurodevelopmental changes, blood Phe levels and dietary Phe tolerance before and after sapropterin therapy; 3) to generate pilot data to assess the feasibility of evaluating brain glucose metabolism with FDG-PET imaging and to explore potential trends resulting from the administration of sapropterin therapy. METHODS: We enrolled 5 subjects, ranged in age from 22 years to 51 years, with PKU. Subjects underwent FDG-PET brain imaging, blood tests for Phe and tyrosine levels, and neurocognitive evaluations before and 4 months after sapropterin therapy (20 mg/kg/day). All subjects' Phe and tyrosine levels were monitored once a week during the study. Subjects kept 3 day diet records that allow calculation of Phe intake. RESULTS: None of the subjects responded to sapropterin therapy based on 30% decrease in blood Phe level. The data show that glucose metabolism appeared depressed in the cerebellum and left parietal cortex while it was increased in the frontal and anterior cingulate cortices in all five subjects. In response to sapropterin therapy, relative glucose metabolism showed significant increases in left Broca's and right superior lateral temporal cortices. Interestingly, there was corresponding enhanced performance in a phonemic fluency test performed during pre- and postneurocognitive evaluation. CONCLUSIONS: Further studies with a larger sample size are needed to confirm the above changes in both sapropterin non-responsive and responsive PKU patients.

Anthropometric predictors of visceral adiposity in normal-weight and obese adolescents.

BACKGROUND: Obesity and fat distribution patterns [subcutaneous vs. visceral adipose tissue (VAT)] are important predictors of future cardiometabolic risk. As accurate VAT measurement entails imaging, surrogate anthropometric measurements that would be cheaper and quicker to obtain would be highly desirable. Sagittal abdominal diameter (SAD) may be better than other VAT surrogate measures in adults, but the value of SAD to predict magnetic resonance imaging (MRI)-determined VAT in adolescents of different races, sexes, and pubertal stages has not been determined. AIM: To test the hypothesis that SAD correlates more strongly with volumetric VAT than other anthropometric measurements, independent of age, sex, race, and Tanner stage. SUBJECTS AND METHODS: Twenty-eight normal-weight and 44 obese adolescents underwent Tanner staging, anthropometric examinations, and abdominal MRI for volumetric partitioned fat calculation. RESULTS: VAT increased exponentially in the body mass index (BMI) > 97th percentile range. SAD, waist circumference (WC), BMI, and BMI Z-score correlated strongly with VAT (correlation coefficients of 0.85-0.86, all p-values < 0.0005); waist-hip ratio was less predictive of VAT (r = 0.68, p < 0.0005). On hierarchical regression, the strongest predictors of VAT in obese subjects were BMI Z-score and SAD (R(2) = 0.34 vs. 0.31, respectively, p < 0.0005); in normal-weight subjects, most anthropometric measures predicted VAT equally (R(2) = 0.16-0.18, p-values = 0.018-0.026). CONCLUSIONS: Unlike adults, in obese adolescents, SAD is not the strongest predictor of visceral adiposity. BMI Z-score is equivalently predictive and, together with BMI, provides sufficient information to assess visceral adiposity; more specialized anthropometric measurements (e.g., SAD and WC) do not add additional predictive value.

Relationship between sleep and pain in adolescents with juvenile primary fibromyalgia syndrome.

STUDY OBJECTIVES: To investigate sleep quality in adolescents with juvenile primary fibromyalgia syndrome (JPFS) and determine whether sleep abnormalities, including alpha-delta sleep (ADS), correlate with pain intensity. We hypothesized that successful treatment for pain with exercise therapy would reduce ADS and improve sleep quality. DESIGN: Single-center preintervention and postintervention (mean = 5.7 ± 1.0 weeks; range = 4.0-7.3 weeks) observational study. PATIENTS: Ten female adolescents (mean age = 16.2 ± 0.65 SD yr) who met criteria for JPFS and completed treatment. INTERVENTIONS: Multidisciplinary pain treatment, including intensive exercise therapy. MEASUREMENTS AND RESULTS: Pain and disability were measured by a pain visual analog scale (VAS) and the functional disability inventory. Subjective sleep measures included a sleep VAS, an energy VAS, and the School Sleep Habits Survey. Objective sleep measures included actigraphy, polysomnography (PSG), and the Multiple Sleep Latency Test. Baseline PSG was compared with that of healthy age- and sex-matched control patients. At baseline, patients had poorer sleep efficiency, more arousals/awakenings, and more ADS (70.3% of total slow wave sleep [SWS] versus 21.9% SWS, P = 0.002) than controls. ADS was unrelated to pain, disability, or subjective sleep difficulty. After treatment, pain decreased (P = 0.000) and subjective sleep quality improved (P = 0.008). Objective sleep quality, including the amount of ADS, did not change. CONCLUSIONS: Although perceived sleep quality improved in adolescents with JPFS after treatment, objective measures did not. Our findings do not suggest exercise therapy for pain improves sleep by reducing ADS, nor do they support causal relationships between ADS and chronic pain or subjective sleep quality.

Comparison of oral and intravenous glucose tolerance test derived sensitivity and secretory indices in obese adolescents.

BACKGROUND: Insulin resistance increases type 2 diabetes risk in obese adolescents. Thus, quantitative tools measuring insulin sensitivity and secretion are important for risk assessment. METHODS: Forty-four obese pubertal adolescents underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). We correlated OGTT-derived whole body sensitivity index (WBISI) with FSIGT-derived insulin sensitivity index (Si). Insulinogenic index (IGI) from OGTT was compared with acute insulin response to glucose (AIRg) from FSIGT. RESULTS: Fasting insulin (r = -.64, P < .0005) and glucose (r = -.39 P ≤ .0005) predicted Si. The OGTT-derived index WBISI correlated with the FSIGT-derived Si (r = .608, P < .0005). IGI correlated with AIRg from FSIGT (r = .704, P < .0005). CONCLUSIONS: OGTT-based measures correlated with FSIGT-derived measures of insulin sensitivity and secretion. In particular, we demonstrated that WBISI can be a reliable alternative to FSIGT-derived Si in clinical settings where OGTT is a more feasible option.

Accuracy of computer algorithms and the human eye in scoring actigraphy.

PURPOSE: The purpose of this study is to determine the optimal scoring method and parameter settings of actigraphy by comparison to simultaneous polysomnography (PSG). METHODS: Fifteen studies of simultaneous PSG and actigraphy were completed in adolescents (mean age = 16.3 years) and analyzed. Scoring actigraphy by the human eye was compared to a commercial computerized algorithm using various parameters. The PSG was considered the reference standard. RESULTS: There was a better correlation between actigraphy and PSG sleep start/end, total sleep time, wake after sleep onset, and sleep efficiency when the rest period was determined by the human (mean r = 0.640) rather than auto-set by the software (r = 0.406). The best results came when the rest intervals were set based on the PSG (r = 0.694). Scoring the printed actogram by the human eye was superior to the auto analyses as well (r = 0.575). Higher correlations and lower biases were obtained from lower wake threshold settings (low and medium) and higher immobility times (10 and 15 min). CONCLUSIONS: Visual scoring by simple inspection of the actigraphy tracing had a reasonable correlation with the gold standard PSG. Accurate determination of the rest interval is important in scoring actigraphy. Scoring actigraphy by the human eye is superior to this computer algorithm when auto-setting major rest periods. A low wake threshold and 10-15 min of immobility for sleep onset and sleep end yield the most accurate computerized results. Auto-setting major rest intervals should be avoided to set start/end of rest intervals; adjustments for artifacts and/or a sleep diary for comparison are helpful.

Upper airway collapsibility and genioglossus activity in adolescents during sleep.

STUDY OBJECTIVES: Obese patients develop obstructive sleep apnea syndrome (OSAS), at least in part because of a narrowed upper airway. However, many obese adolescents do not develop OSAS, despite having a presumably narrower airway. The reasons for this phenomenon are unclear. The authors hypothesized that obese controls have a compensatory neuromuscular response to subatmospheric pressure loads during sleep, making them less likely to develop upper airway collapse. DESIGN: Patients underwent pressure-flow measurements during sleep while wearing intraoral electrodes to measure genioglossal electromyography (EMGgg). Two techniques were applied to decrease nasal pressure (P(N)) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. SETTING: Sleep laboratory. PARTICIPANTS: There were 35 obese patients with OSAS, 28 obese controls, and 43 lean controls. RESULTS: In the activated state, the two control groups had a flatter slope of the pressure-flow relationship and a more negative critical closing pressure (less collapsible) than the OSAS group. In the hypotonic state, the lean controls had a flatter slope of the pressure-flow relationship than the OSAS and obese control groups. In the activated state, the slope of EMGgg versus P(N) was greater in the obese control group than in the OSAS or lean control groups (P = 0.002 and P = 0.028, respectively); there were no differences in the hypotonic state. CONCLUSIONS: Obese controls have vigorous upper airway neuromuscular responses during sleep. Upper airway reflexes normally decline during adolescent development. It is speculated that obese adolescents without OSAS maintain protective upper airway reflexes during adolescent development, whereas those who go on to develop OSAS do not.

Ventilatory responses to hypercapnia during wakefulness and sleep in obese adolescents with and without obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Abnormal ventilatory drive may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). Concomitant with the obesity epidemic, more adolescents are developing OSAS. However, few studies have specifically evaluated the obese adolescent group. The authors hypothesized that obese adolescents with OSAS would have a blunted hypercapnic ventilatory response (HCVR) while awake and blunted ventilatory responses to carbon dioxide (CO(2)) during sleep compared with obese and lean adolescents without OSAS. DESIGN: CVR was measured during wakefulness. During nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, respiratory parameters and genioglossal electromyogram were measured during CO(2) administration in comparison with room air in obese adolescents with OSAS, obese control study participants, and lean control study participants. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-eight obese patients with OSAS, 21 obese control study participants, and 37 lean control study participants. RESULTS: The obese OSAS and obese control groups had a higher HCVR compared with the lean control group during wakefulness. During both sleep states, all 3 groups had a response to CO(2); however, the obese OSAS group had lower percentage changes in minute ventilation, inspiratory flow, inspiratory time, and tidal volume compared with the 2 control groups. There were no significance differences in genioglossal activity between groups. CONCLUSIONS: HCVR during wakefulness is increased in obese adolescents. Obese adolescents with OSAS have blunted ventilatory responses to CO(2) during sleep and do not have a compensatory prolongation of inspiratory time, despite having normal CO(2) responsivity during wakefulness. Central drive may play a greater role than upper airway neuromotor tone in adapting to hypercapnia.

GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K+ channel.

Infants with congenital hyperinsulinism owing to inactivating mutations in the K(ATP) channel (K(ATP)HI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with K(ATP)HI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with K(ATP)HI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid-stimulated insulin secretion in pancreatic islets isolated from neonates with K(ATP)HI. Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in K(ATP)HI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with K(ATP)HI.