RESUMO
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.
Assuntos
Doença de Crohn , Hormônio do Crescimento Humano , Adolescente , Estatura , Criança , Doença de Crohn/complicações , Feminino , Hormônio do Crescimento , Humanos , Fator de Crescimento Insulin-Like I , Interferon gama , Interleucina-1beta , Interleucina-6 , Interleucina-8 , Estudos Longitudinais , Masculino , Estudos ProspectivosRESUMO
Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth. Previous research has focused primarily on White girls, resulting in data gaps regarding male puberty and among potentially high-risk populations. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined body mass index at age 5 years (2005-2006) and multiple markers of pubertal onset, assessed repeatedly and longitudinally at 7 in-person visits, starting at age 9 and continuing through age 14 (2009-2015), among 336 Mexican Americans in Salinas, California. We observed no associations among boys, but found significantly earlier thelarche in overweight (HR = 1.7, 95% CI: 1.1, 2.7) and obese girls (HR = 1.5, 95% CI: 1.0, 2.4), menarche in overweight girls (HR = 1.6; CI: 1.0, 2.4), and pubarche in obese girls (HR = 1.9; CI: 1.2, 3.0), compared with normal-weight girls. This study examined an understudied population and included key covariates, such as birth weight and early adverse events, which are typically omitted in studies.
Assuntos
Americanos Mexicanos/estatística & dados numéricos , Obesidade Infantil/etnologia , Puberdade/fisiologia , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Menarca/fisiologia , Fatores Sociodemográficos , Circunferência da CinturaRESUMO
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.
Assuntos
Aterosclerose/epidemiologia , Espessura Intima-Media Carotídea/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/epidemiologia , Adolescente , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Biomarcadores/análise , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etiologia , Prevalência , Medição de Risco/métodos , Fatores de RiscoRESUMO
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.
Assuntos
Insulina/metabolismo , Transplante de Fígado/efeitos adversos , Estado Pré-Diabético/diagnóstico , Transplantados , Adolescente , Adulto , Fatores Etários , Glicemia/análise , Criança , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Incidência , Resistência à Insulina , Secreção de Insulina , Transplante de Fígado/métodos , Masculino , Análise Multivariada , Estado Pré-Diabético/epidemiologia , Prognóstico , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: Polybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing. METHODS: Study subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones. RESULTS: Prenatal concentrations of all 4 congeners and Æ©PBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for Æ©PBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for Æ©PBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche. CONCLUSIONS: We found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.
Assuntos
Disruptores Endócrinos/toxicidade , Exposição Ambiental , Poluentes Ambientais/toxicidade , Éteres Difenil Halogenados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Puberdade/efeitos dos fármacos , California/epidemiologia , Criança , Feminino , Retardadores de Chama/toxicidade , Humanos , Estudos Longitudinais , Masculino , México/etnologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estudos ProspectivosRESUMO
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Mexican-American children are at particularly high risk of obesity. Features of the perinatal environment, including maternal nutrition, anthropometry, glucose tolerance and growth rate during infancy are implicated in programming of obesity in the offspring. WHAT THIS STUDY ADDS: Greater rate of weight or length gain in the first 6 months of life is associated with lower 9-year child adiponectin levels, adjusting for 9-year child BMI. Nine-year-old child adipokine levels are strongly related to those of their mothers'. OBJECTIVES: To (i) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and (ii) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. METHODS: We measured plasma adiponectin and leptin for 146 mothers-9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas. Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. RESULTS: Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (ß = -2.0, P = 0.04; ß = -8.2, P = 0.02, respectively) adjusting for child body mass index (BMI). We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fibre, sugar-sweetened beverage consumption during pregnancy or children's concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers' levels at the 9-year visit. CONCLUSION: Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children.
Assuntos
Adiponectina/sangue , Fenômenos Fisiológicos da Nutrição Infantil , Leptina/sangue , Americanos Mexicanos/estatística & dados numéricos , Mães , Obesidade/epidemiologia , Índice de Massa Corporal , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Exposição Materna , Inquéritos Nutricionais , Estado Nutricional , Obesidade/etnologia , Obesidade/prevenção & controle , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/psicologia , Nível de Saúde , Qualidade de Vida , Medição de Risco/métodos , Adolescente , Adulto , Atitude Frente a Saúde , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Incidência , Masculino , Prognóstico , Psicometria/métodos , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Bebidas/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Frutose/efeitos adversos , Edulcorantes/efeitos adversos , Ácido Úrico/sangue , Adolescente , Negro ou Afro-Americano , Índice de Massa Corporal , Criança , Dieta , Ingestão de Energia , Feminino , Hispânico ou Latino , Humanos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Estilo de Vida , MasculinoRESUMO
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 microg/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.