RESUMO
To compare patterns of sedentary (SED) time (more sedentary, SED + vs less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA + vs less active, MVPA-), and combinations of behaviors (SED-/MVPA + , SED-/MVPA-, SED + /MVPA + , SED + /MVPA-) regarding nonalcoholic fatty liver diseases (NAFLD) markers. This cross-sectional study included 134 subjects (13.4 ± 2.2 years, body mass index (BMI) 98.9 ± 0.7 percentile, 48.5% females) who underwent 24-h/7-day accelerometry, anthropometric, and biochemical markers (alanine aminotransferase (ALT) as first criterion, and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), AST/ALT ratio as secondary criteria). A subgroup of 39 patients underwent magnetic resonance imaging-liver fat content (MRI-LFC). Hepatic health was better in SED- (lower ALT, GGT, and MRI-LFC (p < 0.05), higher AST/ALT (p < 0.01)) vs SED + and in MVPA + (lower ALT (p < 0.05), higher AST/ALT (p < 0.01)) vs MVPA- groups after adjustment for age, gender, and Tanner stages. SED-/MVPA + group had the best hepatic health. SED-/MVPA- group had lower ALT and GGT and higher AST/ALT (p < 0.05) in comparison with SED + /MVPA + group independently of BMI. SED time was positively associated with biochemical (high ALT, low AST/ALT ratio) and imaging (high MRI-LFC) markers independently of MVPA. MVPA time was associated with biochemical markers (low ALT, high AST/ALT) but these associations were no longer significant after adjustment for SED time. CONCLUSION: Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. WHAT IS KNOWN: ⢠MVPA and SED times are associated with cardiometabolic risks in youths with obesity. ⢠The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. WHAT IS NEW: ⢠Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. ⢠While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.
Assuntos
Alanina Transaminase , Hepatopatia Gordurosa não Alcoólica , Obesidade Infantil , Comportamento Sedentário , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases , Biomarcadores/sangue , Criança , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Humanos , Fígado , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade Infantil/sangue , Obesidade Infantil/fisiopatologiaRESUMO
Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.
Assuntos
Cromossomos Humanos Par 20/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cardiopatias Congênitas/genética , Mapeamento Cromossômico , Estudos de Coortes , Feminino , Genótipo , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: This cross-sectional study analysed the influence of socio-economic factors on screen time, overweight and obesity. METHODS: We asked adolescents aged 10, 14 and 17 from 10 school types in urban and rural regions in Upper Austria to complete questionnaires from December 2012 to February 2013. Their parents were also asked to complete questionnaires. RESULTS: The questionnaires were completed by 2930 adolescents and 2209 parents. Total weekend screen time was significantly associated with a higher body mass index (BMI) in 10-year-old boys (p < 0.005) and 10-year-old girls (p = 0.002), and there were significant associations between higher BMI and television time and longer weekend video game use in subjects aged 10 and 14. Higher education levels were associated with shorter daily video game use and longer computer use. Males (p < 0.0001) and adolescents from immigrant families (p < 0.0001) reported longer screen times at all ages. Lower parental education and higher parental BMI correlated significantly with longer screen time and BMI in the youngest age group. CONCLUSION: The greatest weight problems were in younger adolescents, despite shorter screen times, and boys and adolescents from immigrant families reported the longest screen times. Prevention strategies need to start early.
Assuntos
Índice de Massa Corporal , Obesidade Infantil/epidemiologia , Instituições Acadêmicas/classificação , Tempo de Tela , Inquéritos e Questionários , Televisão/estatística & dados numéricos , Adolescente , Fatores Etários , Áustria , Criança , Estudos Transversais , Educação/métodos , Feminino , Humanos , Incidência , Modelos Lineares , Masculino , Análise Multivariada , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Infantil/etiologia , Medição de Risco , População Rural , Fatores Sexuais , População UrbanaRESUMO
Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (â¼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals.
Assuntos
Variações do Número de Cópias de DNA/genética , Cardiopatias Congênitas/genética , Coração/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Genômica , Genótipo , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not dominant-negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives of patients with AR complete IFN-γR2 deficiency respond poorly to IFN-γ, in some cases as poorly as the cells of P1. Naive CD4(+) T cells and memory IL-4-producing T cells from these individuals also responded poorly to IFN-γ, whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is consistent with the lower levels of expression of IFN-γR2 in lymphoid than in myeloid cells. Overall, MSMD in this patient is probably due to autosomal dominant (AD) IFN-γR2 deficiency, resulting from haploinsufficiency, at least in lymphoid cells. The clinical penetrance of AD IFN-γR2 deficiency is incomplete, possibly due, at least partly, to the variability of cellular responses to IFN-γ in these individuals.
Assuntos
Haploinsuficiência , Infecções por Mycobacterium não Tuberculosas/genética , Receptores de Interferon/genética , Adolescente , Linfócitos B/imunologia , Linfócitos B/metabolismo , Sequência de Bases , Estudos de Casos e Controles , Células Cultivadas , Feminino , Expressão Gênica , Genes Dominantes , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Interferon gama/fisiologia , Infecções por Mycobacterium/genética , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores de Interferon/deficiência , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate.
Assuntos
Predisposição Genética para Doença , Leucócitos/metabolismo , Mutação de Sentido Incorreto , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Antibacterianos/farmacologia , Vacina BCG/efeitos adversos , Vacina BCG/farmacologia , Linhagem Celular , Criança , Pré-Escolar , Glicosilação , Humanos , Técnicas In Vitro , Interleucina-12/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/microbiologia , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/metabolismo , Tunicamicina/farmacologiaRESUMO
Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 ± 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Jejum , Glucagon , Intolerância à Glucose , Teste de Tolerância a Glucose , Humanos , Glucagon/sangue , Diabetes Mellitus Tipo 2/sangue , Adolescente , Masculino , Feminino , Intolerância à Glucose/sangue , Criança , Jejum/sangue , Glicemia/metabolismo , Glicemia/análise , Obesidade Infantil/sangue , Obesidade Infantil/complicações , Insulina/sangueRESUMO
OBJECTIVES: B-type natriuretic peptides have been shown to enable differentiation between heart and lung diseases in adults and children. In neonates, the role of natriuretic peptides for diagnosis of congenital heart defect (CHD) is not yet ascertained. The purpose of this single-center prospective study was to investigate aminoterminal B-type natriuretic peptide concentrations and their time courses during the first 5 days of life in neonates with CHD compared with neonates with respiratory distress. DESIGN: Single-center prospective study. SETTING: Tertiary-care neonatal ICU. PATIENTS: Aminoterminal B-type natriuretic peptide levels of 40 neonates with arterial duct-dependent CHD and of 40 neonates with respiratory distress without CHD were analyzed on the first, second, third, and fifth day of life. MAIN RESULTS: Mean aminoterminal B-type natriuretic peptide concentrations in the CHD group were significantly higher on the second (14191 vs. 4872 pg/mL), third (17790 vs. 3524 pg/mL), and fifth day (17015 vs. 4044 pg/mL), but not on the first day of life. Repeated measurements analysis of variance revealed a significantly different time course of aminoterminal B-type natriuretic peptide concentrations between the two groups. CONCLUSIONS: On the first day of life, aminoterminal B-type natriuretic peptide cannot differentiate between CHD and respiratory distress without CHD in the neonate. From the second day onwards, aminoterminal B-type natriuretic peptide in neonates with CHD shows higher values and a different time course and enables differentiation between CHD and respiratory distress due to other than cardiac reasons.
Assuntos
Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Respiratória/sangue , Insuficiência Respiratória/diagnóstico , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Cardiopatias Congênitas/fisiopatologia , Frequência Cardíaca , Humanos , Recém-Nascido , Masculino , Curva ROC , Insuficiência Respiratória/fisiopatologia , Fatores de TempoRESUMO
PURPOSE OF REVIEW: To present the definitions and recommendations for movement behaviors in children and adolescents, including physical activity (PA), sedentary behaviors (SB), and sleep, and to provide an overview regarding their impact on health and obesity outcomes from childhood to adulthood, as well as interactions with appetite control. RECENT FINDINGS: PA represents a variable proportion of daily energy expenditure and one can be active with high SB or vice versa. Studies have described movements across the whole day on a continuum from sleep to SB to varying intensities of PA. More PA, less SB (e.g., less screen time) and longer sleep are positively associated with indicators of physical health (e.g., lower BMI, adiposity, cardiometabolic risk) and cognitive development (e.g., motor skills, academic achievement). However, less than 10% of children currently meet recommendations for all three movement behaviors. Movement behaviors, adiposity, and related cardiometabolic diseases in childhood track into adolescence and adulthood. Furthermore, low PA/high SB profiles are associated with increased energy intake. Recent studies investigating energy balance regulation showed that desirable movement behavior profiles are associated with better appetite control and improved eating habits. Early identification of behavioral phenotypes and a comprehensive approach addressing all key behaviors that directly affect energy balance will allow for individual strategies to prevent or treat obesity and its comorbidities. Investigating exercise as a potential "corrector" of impaired appetite control offers a promising weight management approach.
Assuntos
Apetite , Doenças Cardiovasculares , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Obesidade , Comportamento Sedentário , Sono , Adulto JovemRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the leading hepatic disease in children, ranging from steatosis to steatohepatitis and fibrosis. Age, sex, hormonal levels, pubertal stages, genetic risk- and epigenetic factors are among the many influencing factors. Appearing predominantly in children with obesity, but not exclusively, it is the liver's manifestation of the metabolic syndrome but can also exist as an isolated entity. SUMMARY: Pediatric NAFLD differs from the adult phenotype. This narrative review on NAFLD in children with obesity provides an overview of the current knowledge on risk factors, screening, and diagnostic methods, as well state-of-the-art treatment. The recent discussion on the proposition of a new nomenclature - Metabolic [Dysfunction-] Associated Liver Disease - is featured, and current gaps of knowledge are discussed. KEY MESSAGES: Currently, there is no international consensus on screening and monitoring of pediatric NAFLD. With lifestyle interventions being the cornerstone of treatment, no registered pharmacological treatment for pediatric NAFLD is available. Development and validation of additional noninvasive biomarkers, scores and imaging tools suitable to subcategorize, screen and monitor pediatric patients are necessary. With a variety of upcoming and promising agents, clear recommendations for pediatric nonalcoholic steatohepatitis trials are urgently needed.
Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Criança , Humanos , Estilo de Vida , Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , ObesidadeRESUMO
Paediatric non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Obesity is the main risk factor. Nutrition and lifestyle are the key elements in preventing and treating NAFLD in the absence of approved drug therapy. Whilst recommendations and studies on macronutrients (carbohydrates, fat and protein) in adult NAFLD exist, the discussion of this topic in paediatric NAFLD remains contradictory. The purpose of this review is to provide state-of-the-art knowledge on the role of macronutrients in paediatric NAFLD regarding quality and quantity. PubMed was searched and original studies and review articles were included in this review. Fructose, sucrose, saturated fatty acids, trans-fatty acids and ω-6-fatty-acids are strongly associated with paediatric NAFLD. High consumption of fibre, diets with a low glycaemic index, mono-unsaturated-fatty-acids and ω-3-fatty-acids reduce the risk of childhood-onset NAFLD. Data regarding the role of dietary protein in NAFLD are contradictory. No single diet is superior in treating paediatric NAFLD, although the composition of macronutrients in the Mediterranean Diet appears beneficial. Moreover, the optimal proportions of total macronutrients in the diet of paediatric NAFLD patients are unknown. Maintaining a eucaloric diet and avoiding saturated fatty acids, simple sugars (mainly fructose) and a high-caloric Western Diet are supported by literature.
RESUMO
Until recently, glucagon was considered a mere antagonist to insulin, protecting the body from hypoglycemia. This notion changed with the discovery of the liver-alpha cell axis (LACA) as a feedback loop. The LACA describes how glucagon secretion and pancreatic alpha cell proliferation are stimulated by circulating amino acids. Glucagon in turn leads to an upregulation of amino acid metabolism and ureagenesis in the liver. Several increasingly common diseases (e.g., non-alcoholic fatty liver disease, type 2 diabetes, obesity) disrupt this feedback loop. It is important for clinicians and researchers alike to understand the liver-alpha cell axis and the metabolic sequelae of these diseases. While most of previous studies have focused on fasting concentrations of glucagon and amino acids, there is limited knowledge of their dynamics after glucose administration. The authors of this systematic review applied PRISMA guidelines and conducted PubMed searches to provide results of 8078 articles (screened and if relevant, studied in full). This systematic review aims to provide better insight into the LACA and its mediators (amino acids and glucagon), focusing on the relationship between glucose and the LACA in adult and pediatric subjects.
Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Glucagon , Adulto , Humanos , Criança , Glucose/metabolismo , Glucagon/metabolismo , Células Secretoras de Glucagon/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fígado/metabolismo , Aminoácidos/metabolismoRESUMO
Background: Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and Methods: Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. Results: SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). Conclusion: SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR.
Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Insulina , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , TriglicerídeosRESUMO
BACKGROUND: Relationships between movement-related behaviours and metabolic health remain underexplored in adolescents with obesity. OBJECTIVES: To compare profiles of sedentary time (more sedentary, SED+ vs. less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA-) and combinations of behaviours (SED-/MVPA+, SED-/MVPA-, SED+/MVPA+, SED+/MVPA-) in regard to metabolic health. METHODS: One hundred and thirty-four subjects (mean age 13.4 ± 2.2 yrs, mean body mass index [BMI] 98.9 ± 0.7 percentile, 48.5% females) underwent 24 h/7 day accelerometry, anthropometric, body composition, blood pressure (BP), lipid profile and insulin resistance (IR) assessments. RESULTS: Metabolic health was better in SED- [lower fat mass (FM) percentage (p < 0.05), blood pressure (BP) (p < 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (p < 0.001) and metabolic syndrome risk score (MetScore) (p < 0.001), higher high-density lipoprotein-cholesterol (HDL-c) (p = 0.001)] vs. SED+ group and in MVPA+ [lower triglyceridemia (TG), (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.001), higher HDL-c (p < 0.01)] vs. MVPA- group after adjustment with age, gender, maturation and BMI. SED-/MVPA+ group had the best metabolic health. While sedentary (p < 0.001) but also MVPA times (p < 0.001) were lower in SED-/MVPA- vs. SED+/MVPA+, SED-/MVPA- had lower FM percentage (p < 0.05), HOMA-IR (p < 0.01) and MetScore (p < 0.05) and higher HDL-c (p < 0.05), independently of BMI. Sedentary time was positively correlated with HOMA-IR and Metscore and negatively correlated with HDL-c after adjustment with MVPA (p < 0.05). MVPA was negatively correlated with HOMA-IR, BP and MetScore and positively correlated with HDL-c after adjustment with sedentary time (p < 0.05). CONCLUSION: Lower sedentary time is associated with a better metabolic health independently of MVPA and might be a first step in the management of pediatric obesity when increasing MVPA is not possible.
Assuntos
Resistência à Insulina , Artes Marciais , Obesidade Infantil , Adolescente , Índice de Massa Corporal , Criança , HDL-Colesterol , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Obesidade Infantil/epidemiologia , Obesidade Infantil/metabolismo , Comportamento Sedentário , Circunferência da CinturaRESUMO
Carbohydrate counting (CHC) is the established form of calculating bolus insulin for meals in children with type 1 diabetes (T1DM). With the widespread use of continuous glucose monitoring (CGM) observation time has become gapless. Recently, the impact of fat, protein and not only carbohydrates on prolonged postprandial hyperglycaemia have become more evident to patients and health-care professionals alike. However, there is no unified recommendation on how to calculate and best administer additional bolus insulin for these two macronutrients. The aim of this review is to investigate: the scientific evidence of how dietary fat and protein influence postprandial glucose levels; current recommendations on the adjustment of bolus insulin; and algorithms for insulin application in children with T1DM. A PubMed search for all articles addressing the role of fat and protein in paediatric (sub-)populations (<18 years old) and a mixed age population (paediatric and adult) with T1DM published in the last 10 years was performed. Conclusion: Only a small number of studies with a very low number of participants and high degree of heterogeneity was identified. While all studies concluded that additional bolus insulin for (high) fat and (high) protein is necessary, no consensus on when dietary fat and/or protein should be taken into calculation and no unified algorithm for insulin therapy in this context exists. A prolonged postprandial observation time is necessary to improve individual metabolic control. Further studies focusing on a stratified paediatric population to create a safe and effective algorithm, taking fat and protein into account, are necessary.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adolescente , Algoritmos , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Gorduras na Dieta/análise , Proteínas Alimentares/análise , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino , Período Pós-Prandial/fisiologiaRESUMO
Metabolic syndrome (MetS) is highly prevalent in children and adolescents with obesity and places them at an increased risk of cardiovascular-related diseases. However, the associations between objectively measured movement-related behaviors and MetS diagnosis remain unexplored in youths with obesity. The aim was to compare profiles of sedentary (SED) time (more sedentary, SED+ vs. less sedentary, SED-), moderate to vigorous physical activity (MVPA) time (more active, MVPA+ vs. less active, MVPA-) and combinations of behaviors (SED-/MVPA+, SED-/MVPA-, SED+/MVPA+, SED+/MVPA-) regarding the MetS diagnosis. One hundred and thirty-four adolescents with obesity (13.4 ± 2.2 years) underwent 24 h/7 day accelerometry, waist circumference (WC), blood pressure (BP), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG) and insulin-resistance (IR) assessments. Cumulative cardiometabolic risk was assessed by using (i) MetS status (usual dichotomic definition) and (ii) cardiometabolic risk z-score (MetScore, mean of standardized WC, BP, IR, TG and inverted HDL-c). SED- vs. SED+ and MVPA+ vs. MVPA- had lower MetS (p < 0.01 and p < 0.001) and MetScore (p < 0.001). SED-/MVPA+ had the lowest risk. While SED and MVPA times were lower in SED-/MVPA- vs. SED+/MVPA+ (p < 0.001), MetScore was lower in SED-/MVPA- independently of body mass index (BMI) (p < 0.05). MVPA, but not SED, time was independently associated with MetS diagnosis (p < 0.05). Both MVPA (p < 0.01) and SED times (p < 0.05) were associated with MetScore independently of each other. A higher MVPA and lower SED time are associated with lower cumulative cardiometabolic risk.
Assuntos
Sistema Cardiovascular/metabolismo , Exercício Físico , Síndrome Metabólica/diagnóstico , Obesidade Infantil/metabolismo , Comportamento Sedentário , Acelerometria , Adolescente , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Criança , HDL-Colesterol/sangue , Feminino , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/prevenção & controle , Análise de Regressão , Fatores de Risco , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
Non-alcoholic fatty liver disease (NAFLD) contributes essentially to the burden of obesity and can start in childhood. NAFLD can progress to cirrhosis and hepatocellular carcinoma. The early phase of NAFLD is crucial because during this time the disease is fully reversible. Pediatric NAFLD shows unique features of histology and pathophysiology compared to adults. Changes in serum iron parameters are common in adult NAFLD and have been termed dysmetabolic iron overload syndrome characterized by increased serum ferritin levels and normal transferrin saturation; however, the associations of serum ferritin, inflammation, and liver fat content have been incompletely investigated in children. As magnetic resonance imaging (MRI) is an excellent measure for the degree of liver steatosis, we applied this method herein to clarify the interaction between ferritin and fatty liver in male adolescents. For this study, one hundred fifty male pediatric patients with obesity and who are overweight were included. We studied a subgroup of male patients with (n = 44) and without (n = 18) NAFLD in whom we determined liver fat content, visceral adipose tissue, and subcutaneous adipose tissue extent with a 1.5T MRI (Philips NL). All patients underwent a standardized oral glucose tolerance test. We measured uric acid, triglycerides, HDL-, LDL-, total cholesterol, liver transaminases, high sensitive CRP (hsCRP), interleukin-6, HbA1c, and insulin. In univariate analysis, ferritin was associated with MRI liver fat, visceral adipose tissue content, hsCRP, AST, ALT, and GGT, while transferrin and soluble transferrin receptor were not associated with ferritin. Multivariate analysis identified hsCRP and liver fat content as independent predictors of serum ferritin in the pediatric male patients. Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.
Assuntos
Biomarcadores/sangue , Ferritinas/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade Infantil/complicações , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Resistência à Insulina , Testes de Função Hepática , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , PrognósticoRESUMO
BACKGROUND: A 12-year-old boy presented to a community hospital with fever, malaise and fatigue. A polymerase chain reaction test of the cerebrospinal fluid was positive for Epstein-Barr virus. Despite intensive care treatment and antiviral drugs, the patient died 1 month after his initial presentation. INVESTIGATIONS: Physical examination, polymerase chain reaction analysis of the cerebrospinal fluid, brain MRI, immunohistochemistry and molecular biological investigations of postmortem brain samples. DIAGNOSIS: Epstein-Barr Virus encephalitis. MANAGEMENT: Aciclovir, intensive care treatment with intubation, sedation, antiepileptic drugs.
Assuntos
Encefalite Viral/diagnóstico , Infecções por Vírus Epstein-Barr/diagnóstico , Aciclovir/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antivirais/uso terapêutico , Encéfalo/patologia , Encéfalo/virologia , Criança , Sedação Consciente , Cuidados Críticos , Encefalite Viral/terapia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Evolução Fatal , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: Austria faces increasing numbers of childhood overweight and obesity. Despite increasing numbers of studies, associations between parental body mass index (BMI) and education and the school type on overweight/obesity in students have not been reported. The objective of this study was to evaluate the influence of these parameters on the genesis of overweight/obesity in a large cohort representative of youth in Upper Austrian. METHODS: A cross-sectional analysis of data from 2930 children and adolescents aged 10, 14 or 17 years from 11 different state school types was conducted. Students and their parents completed a questionnaire and heights and weights were measured. RESULTS: Of the students 16.9% fulfilled the criteria for overweight and 5.6% for obesity, with the highest rates in the 10-year-olds (19.6% and 5.8%, respectively). While no gender differences were present in the youngest age group, the body mass index (BMI) during adolescence remained higher in boys but decreased significantly in girls. Male gender remained a risk factor through all calculations. Boys were overrepresented in schools with lower education levels and more often had BMIs ≥ 85th and ≥95th percentile. Higher parental education levels and lower parental BMIs were associated with lower BMIs of their offspring. Migration was an additional association factor for BMIs ≥ 85th percentile. CONCLUSION: Low parental education levels, higher parental BMIs and migration background were associated with overweight and obesity in 10-year-olds. In adolescence, male gender and higher parental BMIs remained risk factors.
Assuntos
Índice de Massa Corporal , Escolaridade , Emigração e Imigração/estatística & dados numéricos , Obesidade Infantil/epidemiologia , Instituições Acadêmicas , Estudantes/estatística & dados numéricos , Adolescente , Áustria , Criança , Feminino , Humanos , Masculino , Fatores Sexuais , Estatística como AssuntoRESUMO
BACKGROUND: Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. METHODS: Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases. Gene variants that were not observed in a comparably sequenced control dataset of 5492 samples without severe CVM were then subjected to targeted validation in cases and parents. Whole exome sequencing data from 4593 individuals referred for clinical sequencing were used to bolster evidence for the role of candidate genes in CVMs and LSLs. RESULTS: Our analyses revealed 28 candidate variants in 27 genes, including 17 genes not previously associated with a human CVM disorder, and revealed diverse patterns of inheritance among LOF carriers, including 9 confirmed de novo variants in both novel and newly described human CVM candidate genes (ACVR1, JARID2, NR2F2, PLRG1, SMURF1) as well as established syndromic CVM genes (KMT2D, NF1, TBX20, ZEB2). We also identified two genes (DNAH5, OFD1) with evidence of recessive and hemizygous inheritance patterns, respectively. Within our clinical cohort, we also observed heterozygous LOF variants in JARID2 and SMAD1 in individuals with cardiac phenotypes, and collectively, carriers of LOF variants in our candidate genes had a four times higher odds of having CVM (odds ratio = 4.0, 95% confidence interval 2.5-6.5). CONCLUSIONS: Our analytical strategy highlights the utility of bioinformatic resources, including human disease records and model organism phenotyping, in novel gene discovery for rare human disease. The results underscore the extensive genetic heterogeneity underlying non-syndromic LSLs, and posit potential novel candidate genes and complex modes of inheritance in this important group of birth defects.