RESUMO
OBJECTIVE: To identify predictors of changes in height, weight, and body mass index (BMI) in children with attention deficit hyperactivity disorder (ADHD) starting central nervous system (CNS) stimulants. STUDY DESIGN: There were 230 medication-naïve children aged 5-12 years with ADHD who participated in a randomized trial evaluating the impact of CNS stimulants on growth over 30 months. This observational analysis focused on the 141 participants using study medication for 65 or more days in the first 6-months after starting medication. Biometric variables, ADHD, and oppositional defiant disorder symptom scores at medication initiation, and medication use over the study were examined as predictors of changes in standardized (z) height, weight, and BMI. RESULTS: Mean changes in z-BMI, z-weight. and z-height were negative throughout the study. The most consistent predictors of change in z-BMI, z-weight, and z-height were percent days medicated and total medication exposure. Children with lower z-height and z-weight at medication initiation experienced greater z-BMI and z-weight decreases over the first 6 months on medication. Greater appetite suppression during dose optimization predicted greater decreases in z-weight over the entire study and a greater decrease in z-height over the first 6 months on medication. z-weight change correlated with z-height change. Behavioral symptoms did not predict changes in z-BMI, z-weight, or z-height. CONCLUSIONS: How much and how often CNS stimulants are used predicts changes in z-BMI, z-weight, and z-height in children. Even smaller and lighter children may be at risk for decreases in z-weight and z-BMI. Parent ratings of appetite during dose titration may serve as feasible indicators of future weight and height change in children using CNS stimulants. TRIAL REGISTRATION: Clinicialtrials.gov: NCT01109849.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Adolescente , Apetite/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.
Assuntos
Carotenoides/sangue , Resistência à Insulina/etnologia , Resistência à Insulina/fisiologia , Americanos Mexicanos , Adolescente , beta-Criptoxantina/sangue , Índice de Massa Corporal , Criança , HDL-Colesterol/sangue , Cromatografia Líquida/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Feminino , Humanos , Licopeno/sangue , Masculino , Obesidade/sangue , Obesidade/metabolismo , Fenótipo , Fatores de Risco , Texas , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMIâHOMA-IRâAN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.
Assuntos
Acantose Nigricans/fisiopatologia , Doenças Cardiovasculares/etiologia , Resistência à Insulina , Síndrome Metabólica/etiologia , Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Adolescente , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Criança , Feminino , Humanos , Incidência , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Obesidade/complicações , Estados Unidos/epidemiologiaRESUMO
Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited. The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6-17 years). The environments examined were sedentary activity (SA), assessed by recalls from "yesterday" (SAy) and "usually" (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment-insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood-based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA-IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA-IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.
Assuntos
Doenças Cardiovasculares/genética , Interação Gene-Ambiente , Síndrome Metabólica/genética , Americanos Mexicanos/genética , Aptidão Física , Comportamento Sedentário , Adolescente , Glicemia/metabolismo , Índice de Massa Corporal , Criança , Feminino , Variação Genética , Humanos , Funções Verossimilhança , Masculino , Modelos Genéticos , Herança Multifatorial/genética , Fatores de Risco , Circunferência da Cintura/genéticaRESUMO
Background: Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children.Objective: We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children.Design: Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and ß-carotenoid concentrations were measured in â¼570 (α-carotene in 565 and ß-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex.Results: Carotenoid concentrations were highly heritable and significant [α-carotene: heritability (h2) = 0.81, P = 6.7 × 10-11; ß-carotene: h2 = 0.90, P = 3.5 × 10-15]. After adjusting for multiple comparisons, we found significant (P ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; ß-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; ß-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant (P = 0.051) genetic correlations only between ß-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant.Conclusions: The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence ß-carotene and obesity and lipid traits in MA children.
Assuntos
Carotenoides/genética , Americanos Mexicanos/genética , Estado Nutricional , Obesidade/genética , Fenótipo , Característica Quantitativa Herdável , beta Caroteno/genética , Tecido Adiposo/metabolismo , Adolescente , Índice de Massa Corporal , Carotenoides/sangue , Criança , Meio Ambiente , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Obesidade/sangue , Obesidade/metabolismo , Triglicerídeos/sangue , Circunferência da Cintura , beta Caroteno/sangueRESUMO
Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes. MS was defined as ≥3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53 %), pre-diabetes (13 %), acanthosis nigricans (33 %), and MS (19 %) were strikingly prevalent, as were MS components, including abdominal adiposity (32 %) and low HDL-cholesterol (32 %). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68 % heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.
Assuntos
Predisposição Genética para Doença/genética , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Americanos Mexicanos/genética , Gordura Abdominal/patologia , Acantose Nigricans/patologia , Adolescente , Glicemia , Pressão Sanguínea , Criança , HDL-Colesterol/sangue , Análise por Conglomerados , Análise Fatorial , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Epidemiologia Molecular , Sobrepeso/patologia , Fatores de Risco , Texas/epidemiologiaAssuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Hiperinsulinismo/epidemiologia , Americanos Mexicanos/estatística & dados numéricos , Adolescente , Criança , Feminino , Humanos , Funções Verossimilhança , Masculino , México/etnologia , Prevalência , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Texas/epidemiologiaRESUMO
Type 2 diabetes (T2DM) is now a pediatric disease. As in adults, it disproportionately affects ethnic and racial minorities, including Hispanics. The preponderance of Hispanics in south Texas are of Mexican American (MA) heritage. Over the past 16 years, we have accumulated a large cohort of children with diabetes. We have noted distinct differences in numerous parameters between MA children with T2DM and those with type 1 diabetes (T1DM). In order to explore these observations, we have reviewed the records of all children diagnosed with diabetes (n = 669) during the 9 years between January, 1990 and December, 1998 and seen by our pediatric diabetes group. In this cohort were 329 MA, 287 non-Hispanic whites (EA) and 53 African Americans. Compared to EA children with T1DM, MA children were more likely to have a parent with diabetes, to be hospitalized at the time of diagnosis and to lack health insurance. The differences between MA children with T1DM and T2DM were significant: specifically, children with T2DM were more likely to be female and pubertal with a body mass index >25 kg/m(2) and have acanthosis nigricans. Slightly more than 2/3 of the MA children with T2DM had at least one parent already diagnosed with T2DM. Less than 1/3 of the children with T2DM required hospitalization at the time of diagnosis and only a 1/4 have private health insurance. Over this 9-year interval, the apparent incidence of diabetes almost tripled in south Texas with the great majority of that increase due to the increasing numbers of children with T2DM.