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Objectives: To examine the underlying mechanisms that lead growth impairment to occur more commonly in males than females with Crohn's disease (CD).Study Design: Children and adolescents with CD were enrolled in a prospective multicenter longitudinal cohort study. Height Z-score difference was computed as height Z-score based on chronological age (height chronological age-Z-score) minus height Z-score based on bone age (height bone age-Z-score) using longitudinal data. Specific serum cytokines were measured, hormone Z-scores were calculated based on bone age (bone age-Z), and their longitudinal associations were examined.Results: There were 122 children with CD (63% male) who completed 594 visits. The mean ± SD chronological age was 11.70 ± 1.79 years. The mean ± SD height chronological age-Z-score was -0.03 ± 0.99 in males and -0.49 ± 0.87 in females. The mean ± SD height bone age-Z-score was 0.23 ± 0.93 in males and 0.37 ± 0.96 in females. The magnitude of the mean height Z-score difference was greater in females (-0.87 ± 0.94) than males (-0.27 ± 0.90; P = .005), indicating growth was better in females than males. The following negative associations were identified: in females, interleukin (IL)-8 (P < .001) and IL-12p70 (P = .035) with gonadotropin-bone age-Z-scores; IL-8 (P = .010), IL-12p70 (P = .020), and interferon-γ (P = .004) with sex hormone-bone age-Z-scores, and IL-8 (P = .044) and interferon-γ (P < .001) with insulin-like growth factor 1-bone age-Z-scores; in males, IL-1 beta (P = .019) and IL-6 (P = .025) with insulin-like growth factor 1-bone age-Z-scores.Conclusions: Our data suggest that sex-specific molecular pathways lead to growth impairment in children with CD (primarily growth hormone/insulin-like growth factor-1 axis in males and primarily hypothalamic-pituitary-gonadal axis in females). Mapping these sex-specific molecular pathways may help in the development of sex-specific treatment approaches targeting the underlying inflammation characteristic of CD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how adolescents with or at risk for type 2 diabetes mellitus (T2DM) and their parent/guardians (parents) perceive adolescents’ health-related quality of life. Study design: We interviewed overweight/obese, 12- to 18-year-old youth with T2DM, prediabetes, or insulin resistance and one parent from 5 US sites. Assessments included Pediatric Quality of Life Inventory (PedsQL), Health Utilities Index, family conflict, and diabetes burden. Results: In 108 adolescents, diagnoses included 40.7% with T2DM, 25.0% with prediabetes, and 34.3% with insulin resistance. PedsQL summary score (SS) was higher in adolescents than parents (P =.02). Parents rated physical functioning lower than adolescents (P <.0001), but there were no differences in psychosocial health. Adolescent PedsQL SS did not differ with diagnosis, but was inversely associated with adolescent body mass index z-score (P =.0004) and family conflict (P <.0001) and associated with race/ethnicity (P <.0001). Number of adolescent co-morbidities (P =.007) and burden of diabetes care (P <.05) were inversely associated with parent PedsQL SS. There were no differences in the Health Utilities Index-Mark 3 multi-attribute utility score. Conclusions: Parents perceive their adolescents’ physical functioning as more impaired than adolescents themselves. Contextual factors including severity of obesity, race/ethnicity, family conflict, and burden of diabetes care influence health-related quality of life. Family-based approaches to treatment and prevention of T2DM may benefit from increased attention to the biopsychosocial context. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether sugar-sweetened beverage consumption, a significant source of dietary fructose, is associated with higher serum uric acid levels and blood pressure in adolescents. Study design: We analyzed cross-sectional data from 4867 adolescents aged 12 to 18 years in the National Health and Nutrition Examination Survey, 1999-2004. Dietary data were assessed from 24-hour dietary recall interviews. Sugar-sweetened beverages included fruit drinks, sports drinks, soda, and sweetened coffee or tea. We used multivariate linear regression to evaluate the association of sugar-sweetened beverage consumption with serum uric acid and with blood pressure. Results: Adolescents who drank more sugar-sweetened beverages tended to be older and male. In the adjusted model, serum uric acid increased by 0.18 mg/dL and systolic blood pressure z-score increased by 0.17 from the lowest to the highest category of sugar-sweetened beverage consumption (P for trend, .01 and .03, respectively). Conclusions: These results from a nationally representative sample of US adolescents indicate that higher sugar-sweetened beverage consumption is associated with higher serum uric acid levels and systolic blood pressure, which may lead to downstream adverse health outcomes. [Copyright &y& Elsevier]

Objective: To assess the use of oral glucose tolerance testing (OGTT) to predict efficacy of insulin sensitization (metformin) or suppression (octreotide) because insulin resistance and insulin hypersecretion may impact pharmacotherapeutic efficacy in obese children. Study design: Forty-three and 24 obese children, with and without central nervous system (CNS) insult, underwent OGTT. Insulin sensitivity was expressed as composite insulin sensitivity index (CISI), and secretion as corrected insulin response (CIRgp). Those without CNS insult received metformin (weight-based dosing) for 6 to 16 months. Those with CNS insult received octreotide SQ 15 μg/kg/d for 6 months. Body mass index (BMI) and z-score responses were modeled using CIRgp and CISI. Results: Metformin: With CIRgp and CISI = 1, BMI z-score in white children declined by 0.23 over the first 4 months (P < .001), and by 0.14 over the next year (P = .33). Each 2-fold increase in CIRgp or CISI attenuated BMI z-score reduction, but with wide uncertainty (P = .24). Black children exhibited little response. Octreotide: With CIRgp and CISI = 1, BMI z-score decreased by 0.23 in the first 4 months (P = .052). Efficacy was dependent on an interaction between CIRgp and CISI (P = .051). Conclusions: Efficacy of metformin was predicted by pretreatment insulin resistance. Efficacy of octreotide was predicted by insulin hypersecretion and sensitivity. [Copyright &y& Elsevier]

Objective: To investigate prevalence and predictors of cardiovascular risk in pediatric liver transplant recipients using noninvasive markers of subclinical atherosclerosis: carotid intima-media thickness (cIMT) and aorta intima-media thickness (aIMT).Study Design: Cross-sectional study of 88 pediatric liver transplant recipients. The cIMT and aIMT were measured by ultrasound imaging using standardized protocol.Results: Participants were 15.4 ± 4.8 years of age, and 11.2 ± 5.6 years post-transplantation. The cIMT and aIMT were both higher in males than females. In analyses adjusted for sex, age, and height, the cIMT was higher in subjects transplanted for chronic/cirrhotic liver disease and lower in subjects on cyclosporine (n = 9) than tacrolimus (n = 71). The cIMT was not associated with rejection history or current corticosteroid use. The cIMT increased with increasing diastolic blood pressure and triglycerides. The aIMT (n = 83) also increased with age, and its rate of increase post-transplant varied by age at transplantation. In adjusted analyses, aIMT was higher in subjects with glucose intolerance. In analysis of patients ≤20 years of age for whom blood pressure percentiles could be calculated (n = 66), aIMT increased with increasing diastolic blood pressure percentile (0.010 mm per 5-percentile; 95% CI, 0.000-0.021; P = 0.05). Neither the cIMT nor the aIMT was associated with obesity, systolic hypertension, or other dyslipidemia at study visit.Conclusion: Measures of long-term cardiovascular risk were associated with conditions that are more common in pediatric liver transplant recipients than nontransplanted peers, namely, diastolic hypertension and glucose intolerance. Larger, longitudinal studies are warranted to investigate whether cIMT could be useful for stratifying these patients' cardiovascular risk-and potential need for proactive intervention-during long-term follow-up. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths.Study Design: This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL). Corrected insulin response (CIR) was calculated as measure of insulin secretion, corrected for glucose (CIR30, CIR60, CIR120).Results: Subjects were aged 8.1-30.0 years and 1.1-24.7 years post-transplant; 44% had prediabetes-27% IGT, 14% IFG, and 3% both. IGT was characterized by insulin hyposecretion, with lower CIR60 and CIR120 in IGT than subjects with normal glucose tolerance. Subjects with tacrolimus trough >6 µg/mL at study visit had lower CIR120 than those with trough ≤6 µg/mL and those off calcineurin-inhibitors. Mean of tacrolimus troughs preceding the study visit, years since transplant, and rejection episodes were not associated significantly with lower CIR. CIR suppression by tacrolimus was most pronounced >6 years from transplant. Overweight/obese subjects and adolescents who retained normal glucose tolerance had greater CIR than those who were IGT.Conclusion: IGT after pediatric liver transplant is driven by inadequate insulin secretion. It is quite common but not detectable with fasting laboratory values-the screening recommended by current guidelines. Calcineurin inhibitors suppress insulin secretion in these patients in a dose-dependent manner. Given the recent focus on long-term outcomes and immunosuppression withdrawal in these children, longitudinal studies are warranted to investigate whether IGT is reversible with calcineurin inhibitor minimization. [ABSTRACT FROM AUTHOR]

Objectives: To assess insulin dynamics to oral glucose tolerance testing in obese children, denoting individual contributions of insulin hypersecretion versus resistance to racial and etiopathogenetic specificity., Study Design: We performed 3-hour oral glucose tolerance testing in 113 nondiabetic obese children (age 13.6 +/- 3.1 years; 41 male, 78 female; 37 black, 41 white; 35 with central nervous system [CNS] insult). The corrected insulin response (CIRgp; measuring beta-cell secretion) and the composite insulin sensitivity index (CISI) were computed and log-transformed, and each was modeled in terms of the other, plus race/etiology, age, sex, body mass index z score, glucose tolerance, pubertal status, and geographic location., Results: A scatterplot of logCIRgp versus logCISI showed that racial and etiopathogenetic groups plotted in different areas. CISI (controlled for CIRgp and other variables) was only 13% lower in blacks than in whites ( P = .32). Conversely, CIRgp (controlled for CISI and other variables) was 49% higher in blacks ( P = .028). CNS insult exhibited a 40% higher CIRgp ( P = .054) and 11% higher CISI ( P = .42) than intact white subjects., Conclusions: Insulin hypersecretion and resistance are distinct phenomena in childhood obesity. Insulin hypersecretion appears to be the more relevant insulin abnormality both in obese blacks and in CNS insult.