RESUMEN
AIM: Previous studies suggest a lack of a unified approach in identifying and addressing children with obesity while being inpatients in individual Australian hospitals. Our study aimed to describe current clinical practice across Australia and identify discrepancies that can aid in developing a more unified response to children identified with obesity as hospital inpatients. METHODS: A cross-sectional exploratory online survey was distributed to major paediatric in-patient departments in Australia, with a response rate of 68%. Questions focused on education, identification, interventions and attitudes towards a national protocol. RESULTS: Twenty percent of respondents indicated that staff in their department regularly record body mass index, 66% address weight issues and only 8% consistently refer to appropriate outpatient services. Although 88% of respondents believe that a national protocol for addressing paediatric obesity would be beneficial, respondents emphasised concerns regarding their local resources. CONCLUSION: Our study can inform the development of a guideline for a unified response to opportunistically identify children with overweight and obesity as inpatients.
Asunto(s)
Obesidad Infantil , Humanos , Australia , Estudios Transversales , Obesidad Infantil/diagnóstico , Niño , Masculino , Femenino , Encuestas y Cuestionarios , Pautas de la Práctica en Medicina/estadística & datos numéricos , Índice de Masa Corporal , AdolescenteRESUMEN
Replicating the human genome efficiently and accurately is a daunting challenge involving the duplication of upward of three billion base pairs. At the core of the complex machinery that achieves this task are three members of the B family of DNA polymerases: DNA polymerases α, δ, and ε. Collectively these multimeric polymerases ensure DNA replication proceeds at optimal rates approaching 2 × 103 nucleotides/min with an error rate of less than one per million nucleotides polymerized. The majority of DNA replication of undamaged DNA is conducted by DNA polymerases δ and ε. The DNA polymerase α-primase complex performs limited synthesis to initiate the replication process, along with Okazaki-fragment synthesis on the discontinuous lagging strand. An increasing number of human disorders caused by defects in different components of the DNA-replication apparatus have been described to date. These are clinically diverse and involve a wide range of features, including variable combinations of growth delay, immunodeficiency, endocrine insufficiencies, lipodystrophy, and cancer predisposition. Here, by using various complementary approaches, including classical linkage analysis, targeted next-generation sequencing, and whole-exome sequencing, we describe distinct missense and splice-impacting mutations in POLA1 in five unrelated families presenting with an X-linked syndrome involving intellectual disability, proportionate short stature, microcephaly, and hypogonadism. POLA1 encodes the p180 catalytic subunit of DNA polymerase α-primase. A range of replicative impairments could be demonstrated in lymphoblastoid cell lines derived from affected individuals. Our findings describe the presentation of pathogenic mutations in a catalytic component of a B family DNA polymerase member, DNA polymerase α.
Asunto(s)
ADN Polimerasa I/genética , ADN Primasa/genética , Enfermedades Genéticas Ligadas al Cromosoma X/etiología , Trastornos del Crecimiento/etiología , Hipogonadismo/etiología , Discapacidad Intelectual/etiología , Microcefalia/etiología , Mutación , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Genotipo , Trastornos del Crecimiento/patología , Humanos , Hipogonadismo/patología , Lactante , Discapacidad Intelectual/patología , Masculino , Microcefalia/patología , Persona de Mediana Edad , Linaje , Secuenciación del ExomaRESUMEN
Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM.
Asunto(s)
Citoesqueleto de Actina/metabolismo , Glucosa/metabolismo , Tropomiosina/metabolismo , Células 3T3 , Adipocitos/metabolismo , Animales , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Miosina Tipo I/metabolismo , Unión Proteica , Transporte de Proteínas , Tropomiosina/genéticaRESUMEN
PURPOSE: Poor cardiorespiratory fitness is associated with increased all cause morbidity and mortality. In children with obesity, maximum oxygen uptake (VÌO2max) may not be achieved due to reduced motivation and peripheral fatigue. We aimed to identify a valid submaximal surrogate for VÌO2max in children with obesity. METHOD: Ninety-two children with obesity (7-16 years) completed a maximal exercise treadmill test and entered a three-month exercise and/or nutrition intervention after which the exercise test was repeated (n = 63). Participants were required to reach VÌO2max to be included in this analysis (n = 32 at baseline and n = 13 at both time-points). The oxygen uptake efficiency slope (OUES) was determined as the slope of the line when VÌO2 (L/min) was plotted against log VÌE. Associations between the maximal OUES, submaximal OUES (at 3, 4, 5 and 6 min of the exercise test) and VÌO2max were calculated. RESULTS: In the cross-sectional analysis, VÌO2max (L/min) was strongly correlated with 5-min OUES independent of Tanner puberty stage and sex (R2 = .80, p < .001). Longitudinal changes in VÌO2max were closely reflected by changes in 5-min OUES independent of change in percent body fat (R2 = .63, p < .05). CONCLUSION: The 5-min OUES is a viable alternative to VÌO2max when assessing children with obesity.
Asunto(s)
Capacidad Cardiovascular , Consumo de Oxígeno , Obesidad Infantil/fisiopatología , Adolescente , Niño , Estudios Transversales , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Obesidad Infantil/terapia , Valores de ReferenciaRESUMEN
AIMS: The aim of this study was to identify factors that predict risk of obstructive sleep apnoea (OSA) in obese children, which could aid in prioritising sleep studies. METHODS: A retrospective chart review was undertaken of obese children seen in the KOALA weight management clinic and Sleep clinic. Data collected included demographics, clinical history, examination findings, biochemical markers, and polysomnogram results. RESULTS: Two hundred seventy-two obese children were seen in the KOALA clinic out of which 54 (20%) were also seen in the Sleep clinic because of snoring. Thirty-two were referred by the KOALA clinic; the remaining 22 were referred by other medical practitioners prior to being seen in the KOALA clinic. Thirty-nine had polysomnograms. The time from referral to Sleep clinic ranged from 10 days to 1.5 years with 50% seen within 6 months; with similar time gap between the blood tests and time of polysomnograms. Thirty-six percent (14/39) were reported to have OSA. Six children were Aboriginal/Torres Strait Islander (ATSI) and all had OSA, which was statistically significant (P = 0.004). There was a statistically significant correlation between high-sensitivity C-reactive protein (hs-CRP) and obstructive event index (OEI) in rapid eye movement (REM) sleep. (r = 0.50, P = 0.04). Correlation between low-density lipoprotein (LDL) and OEI in REM was r = 0.36, P = 0.06, which approached significance. CONCLUSIONS: Ethnicity was a significant factor with more obese ATSI children having OSA. The significant correlation between hs-CRP with OEI is consistent with findings of previous studies. Several factors (glycosylated haemoglobin, LDL) approached significance.
Asunto(s)
Obesidad Infantil/diagnóstico , Obesidad Infantil/epidemiología , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiología , Adolescente , Distribución por Edad , Índice de Masa Corporal , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Polisomnografía , Queensland/epidemiología , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Estadísticas no ParamétricasRESUMEN
AIMS: The overall purpose of this study was to examine the relationship between motor proficiency and health-related fitness in children. In addition, the study aimed to determine if particular combinations of motor skills have a stronger relationship with individual health-related fitness measures. METHODS: Seventy-seven children (F:28, M:49) (mean age: 11.19 ± 2.74 years) participated in this prospective cohort study. Physical measures included the following: motor proficiency (Bruininks-Oseretsky Test of Motor Proficiency, Second Edition), body mass index (BMI), waist circumference, blood pressure, heart rate and VO(2) peak (mL/kg/min). RESULTS: After factoring in age, motor proficiency as a combined total score had a strong negative relationship with the health-related fitness measures of BMI (r (2) = 0.62, P < 0.001) and waist circumference (r (2) = 0.72, P < 0.001) and a strong positive relationship with VO2 peak (r (2) = 0.78, P = 0.002). Children with lower motor proficiency (≤25th percentile) had a significantly larger mean waist circumference (M = 13.85 cm, 95% confidence interval (CI) (2.05, 25.66), P = 0.01), heavier weight (M = 22.17 kg, 95% CI (2.44, 41.91), P = 0.02) and higher BMI (M = 5.10 kg/m(2) , 95% CI (0.33, 9.87), P = 0.03) than children with higher motor proficiency (≤75th percentile). CONCLUSIONS: Motor proficiency, once corrected for age, is significantly related to a number of health-related measures in children and should therefore be considered a focus for investigation for children with poor health-related fitness (e.g. high BMI and waist circumference percentiles or low cardiorespiratory fitness), as motor incompetence could be an underlying contributing factor to a child's poor physical health.
Asunto(s)
Destreza Motora/fisiología , Aptitud Física/fisiología , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
This study explored current physiotherapy practice trends for management of children who are overweight or obese. The professional needs of physiotherapists working with this population were also assessed, including the perceived need for physiotherapy clinical guidelines for prevention and management of children with obesity. A cross-sectional survey design was used, with questionnaires purposefully distributed through 13 key physiotherapy services throughout Australia. Snowball sampling resulted in completed questionnaires from 64 physiotherapists who provided services to children. Half (n=33, 52%) of respondents provided services specifically to overweight or obese children. Of those providing services, one-quarter had prior training specific to working with this population. Most used multi-disciplinary models (n=16, 76%) and provided under 5h of obesity-related services each week (n=29, 88%). Half (n=16, 49%) used body mass index as an outcome measure but more (n=25, 76%) used bodyweight. Only 14 (42%) assessed motor skills. The majority of respondents (n=57, 89%) indicated a need for physiotherapy guidelines to best manage overweight and obese children. Professional development priorities included: 'Educating children and families', 'Assessment methods' and 'Exercise prescription' for overweight and obese children. This data provides workforce intelligence to guide future professional training and inform development of clinical guidelines for physiotherapists in prevention and management of children with obesity and related chronic disease.
Asunto(s)
Obesidad Infantil/rehabilitación , Modalidades de Fisioterapia , Adolescente , Australia , Niño , Estudios Transversales , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Masculino , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
AIM: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children; (ii) To examine the implications for identifying short stature and eligibility for GH treatment. METHODS: Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. RESULTS: Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. CONCLUSIONS: Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.
Asunto(s)
Estatura/fisiología , Centers for Disease Control and Prevention, U.S./normas , Desarrollo Infantil , Organización Mundial de la Salud , Adolescente , Factores de Edad , Niño , Fenómenos Fisiológicos Nutricionales Infantiles , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Guías como Asunto , Humanos , Masculino , Estándares de Referencia , Factores Sexuales , Estados Unidos , Australia OccidentalRESUMEN
UNLABELLED: Caveolin-1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis. Using newly generated pure Balb/C CAV1 null ((Balb/C)CAV1-/-) mice, CAV1-/- mice from Jackson Laboratories ((JAX)CAV1-/-), and CAV1-/- mice developed in the Kurzchalia Laboratory ((K)CAV1-/-), we show that under physiological conditions CAV1 expression in mouse tissues is necessary to guarantee an efficient progression of liver regeneration and mouse survival after partial hepatectomy. Absence of CAV1 in mouse tissues is compensated by the development of a carbohydrate-dependent anabolic adaptation. These results were supported by extracellular flux analysis of cellular glycolytic metabolism in CAV1-knockdown AML12 hepatocytes, suggesting cell autonomous effects of CAV1 loss in hepatic glycolysis. Unlike in (K)CAV1-/- livers, in (JAX)CAV1-/- livers CAV1 deficiency is compensated by activation of anabolic metabolism (pentose phosphate pathway and lipogenesis) allowing liver regeneration. Administration of 2-deoxy-glucose in (JAX)CAV1-/- mice indicated that liver regeneration in (JAX)CAV1-/- mice is strictly dependent on hepatic carbohydrate metabolism. Moreover, with the exception of regenerating (JAX)CAV1-/- livers, expression of CAV1 in mice is required for efficient hepatic lipid storage during fasting, liver regeneration, and diet-induced steatosis in the three CAV1-/- mouse strains. Furthermore, under these conditions CAV1 accumulates in the lipid droplet fraction in wildtype mouse hepatocytes. CONCLUSION: Our data demonstrate that lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions.
Asunto(s)
Caveolina 1/metabolismo , Metabolismo Energético/fisiología , Glucosa/metabolismo , Regeneración Hepática/fisiología , Análisis de Varianza , Animales , Análisis Químico de la Sangre , Proliferación Celular , Cromatografía en Capa Delgada/métodos , Desoxiglucosa/farmacología , Modelos Animales de Enfermedad , Femenino , Hepatectomía , Hepatocitos/metabolismo , Hepatocitos/fisiología , Homeostasis , Metabolismo de los Lípidos/fisiología , Regeneración Hepática/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily of ligand-inducible DNA transcription factors, and is the major mediator of male sexual development, prostate growth and the pathogenesis of prostate cancer. Cell and gene specific regulation by the AR is determined by availability of and interaction with sets of key accessory cofactors. Ski-interacting protein (SKIP; SNW1, NCOA62) is a cofactor shown to interact with several NRs and a diverse range of other transcription factors. Interestingly, SKIP as part of the spliceosome is thought to link mRNA splicing with transcription. SKIP has not been previously shown to interact with the AR. RESULTS: The aim of this study was to investigate whether SKIP interacts with the AR and modulates AR-dependent transcription. Here, we show by co-immunoprecipitation experiments that SKIP is in a complex with the AR. Moreover, SKIP increased 5α-dihydrotestosterone (DHT) induced N-terminal/C-terminal AR interaction from 12-fold to almost 300-fold in a two-hybrid assay, and enhanced AR ligand-independent AF-1 transactivation. SKIP augmented ligand- and AR-dependent transactivation in PC3 prostate cancer cells. Live-cell imaging revealed a fast (half-time=129 s) translocation of AR from the cytoplasm to the nucleus upon DHT-stimulation. Förster resonance energy transfer (FRET) experiments suggest a direct AR-SKIP interaction in the nucleus upon translocation. CONCLUSIONS: Our results suggest that SKIP interacts with AR in the nucleus and enhances AR-dependent transactivation and N/C-interaction supporting a role for SKIP as an AR co-factor.
Asunto(s)
Coactivadores de Receptor Nuclear/metabolismo , Receptores Androgénicos/metabolismo , Animales , Células COS , Línea Celular Tumoral , Núcleo Celular/metabolismo , Chlorocebus aethiops , Dihidrotestosterona/farmacología , Transferencia Resonante de Energía de Fluorescencia , Genes Reporteros , Células HEK293 , Humanos , Inmunoprecipitación , Masculino , Coactivadores de Receptor Nuclear/genética , Unión Proteica/efectos de los fármacos , Estructura Terciaria de Proteína , Receptores Androgénicos/química , Receptores Androgénicos/genética , Activación TranscripcionalRESUMEN
BACKGROUND AND OBJECTIVES: It is unknown to what degree general practitioners (GPs) are able to diagnose and assist in the management of children with type 1 diabetes (T1D). This study examined the experiences of GPs when faced with paediatric T1D. METHOD: A qualitative study using semistructured interviews was conducted with a sample of GPs in Western Sydney. Data were analysed thematically. RESULTS: Thirty GPs reported varied experiences with paediatric T1D. Two themes emerged: 'You don't think of T1D everyday' (GPs do not frequently encounter T1D) and 'We need to be equipped' (despite low patient numbers, GPs want to be able to recognise, refer and assist in the management of children with T1D). DISCUSSION: There is limited Australian research into GPs' ability to diagnose and manage children with T1D. This study highlights the current level of knowledge and referral practices of a sample of GPs.
Asunto(s)
Diabetes Mellitus Tipo 1 , Humanos , Niño , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/terapia , Nueva Gales del Sur , Australia , Actitud del Personal de Salud , Atención Primaria de SaludRESUMEN
Complete androgen insensitivity syndrome (CAIS), where 46,XY individuals present as female, is caused by variants in the androgen receptor gene (AR). We analyzed the DNA of a patient with suspected CAIS using a targeted gene sequencing panel and whole exome sequencing (WES) but did not detect any small nucleotide variants in AR. Analysis of WES data using our bioinformatics pipeline designed to detect copy number variations (CNV) uncovered a rare duplication of exon 2 of AR. Using array comparative genomic hybridization, the duplication was found to span 43.6 kb and is predicted to cause a frameshift and loss of AR protein. We confirmed the power of our WES-CNV detection protocol by identifying pathogenic CNVs in FSHR and NR5A1 in previously undiagnosed patients with disorders of sex development. Our findings illustrate the usefulness of CNV analysis in WES data to detect pathogenic genomic changes that may go undetected using only standard analysis protocols.
Asunto(s)
Síndrome de Resistencia Androgénica , Variaciones en el Número de Copia de ADN , Síndrome de Resistencia Androgénica/genética , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN/genética , Exoma/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Secuenciación del Exoma/métodosAsunto(s)
Nativos de Hawái y Otras Islas del Pacífico , Apnea Obstructiva del Sueño , Australia , Niño , Humanos , ObesidadRESUMEN
BACKGROUND: Childhood obesity is associated with the early development of diseases such as type 2 diabetes and cardiovascular disease. Unfortunately, to date, traditional methods of research have failed to identify effective prevention and treatment strategies, and large numbers of children and adolescents continue to be at high risk of developing weight-related disease. AIM: To establish a unique 'biorepository' of data and biological samples from overweight and obese children, in order to investigate the complex 'gene × environment' interactions that govern disease risk. METHODS: The 'Childhood Overweight BioRepository of Australia' collects baseline environmental, clinical and anthropometric data, alongside storage of blood samples for genetic, metabolic and hormonal profiles. Opportunities for longitudinal data collection have also been incorporated into the study design. National and international harmonization of data and sample collection will achieve required statistical power. RESULTS: Ethical approval in the parent site has been obtained and early data indicate a high response rate among eligible participants (71%) with a high level of compliance for comprehensive data collection (range 56% to 97% for individual study components). Multi-site ethical approval is now underway. CONCLUSIONS: In time, it is anticipated that this comprehensive approach to data collection will allow early identification of individuals most susceptible to disease, as well as facilitating refinement of prevention and treatment programs.
Asunto(s)
Investigación Biomédica , Bases de Datos Factuales , Obesidad , Adolescente , Australia , Niño , Preescolar , Comorbilidad , Recolección de Datos , Humanos , Obesidad/genética , Sobrepeso , Factores de Riesgo , Pérdida de PesoRESUMEN
The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb betaDeltaE in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb betaDeltaE expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb beta siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb beta expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb beta was recruited to the Srebp-1c promoter. Moreover, Rev-erb beta trans-activated the Srebp-1c promoter, in contrast, Rev-erb beta efficiently repressed the Rev-erb alpha promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb beta; and (ii) increased Rev-erb beta and Srebp-1c mRNA expression. These data suggest that Rev-erb beta has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.
Asunto(s)
Músculo Esquelético/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Represoras/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Activación Transcripcional , Animales , Secuencia de Bases , Línea Celular , Electroporación , Hemina/farmacología , Miembro Posterior , Lipogénesis/genética , Ratones , Datos de Secuencia Molecular , Músculo Esquelético/citología , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/biosíntesis , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/agonistas , Proteínas Represoras/genéticaRESUMEN
BACKGROUND: There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D(3) and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. OBJECTIVE: To determine the relationship between measured 25(OH)-vitamin D(3) levels and the degree of acidosis in children at diagnosis with T1DM. SUBJECTS: Children presenting with new-onset T1DM at a tertiary children's hospital. METHODS: 25(OH)-vitamin D(3) and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D(3) levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. RESULTS: Fourteen of the 64 children had low 25(OH)-vitamin D(3) levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r(2) = 0.20, p < 0.001) and ethnic background a further 10% (partial r(2) = 0.10, p = 0.002). The levels of 25(OH)-vitamin D(3) increased in 10 of the 11 children with resolution of the acidosis. CONCLUSIONS: Acid-base status should be considered when interpreting 25(OH)-vitamin D(3) levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.
Asunto(s)
Colecalciferol/sangre , Diabetes Mellitus Tipo 1/sangre , Cetoacidosis Diabética/sangre , Edad de Inicio , Bicarbonatos/sangre , Índice de Masa Corporal , Niño , Preescolar , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Lactante , Masculino , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Background: Increased visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Accurate quantification of VAT is available through magnetic resonance imaging (MRI), which incurs a significant financial and time burden. We aimed to assess the accuracy of dual-energy X-ray absorptiometry- (DXA-) derived VAT (DXA-VAT) against a gold standard MRI protocol (MRI-VAT) in children with normal weight and obesity cross-sectionally, and over the course of a lifestyle intervention. Methodology: MRI-VAT and DXA-VAT were quantified in 61 children (30 normal weight and 31 with obesity) at baseline. Children with obesity entered a three-month exercise and/or nutrition intervention after which VAT was reassessed. MRI- and DXA-VAT cross-sectional area, volume, and mass were quantified, and associations were calculated at baseline (n = 61) and pre-post intervention (n = 28, 3 participants dropped out). Method agreement was assessed through Bland-Altman analysis, linear regression, and Passing-Bablok regression. Results: At baseline, all DXA- and MRI-VAT outcomes were strongly associated (r = 0.90, P < 0.001). However, there were no significant associations between absolute or relative change in DXA- and MRI-VAT outcomes (r = 0.25-0.36, P > 0.05). DXA significantly overestimated VAT CSA (cross-sectional area), volume, and mass when compared with MRI (P < 0.001) at baseline. Significant proportional bias was observed for all DXA-VAT outcomes at baseline and for relative longitudinal changes in DXA-VAT. Conclusions: Although DXA-VAT outcomes were strongly associated with MRI-VAT outcomes at baseline, estimates were subject to proportional bias in children with obesity and normal weight. DXA lacks validity for detecting changes in VAT among children with obesity. This trial is registered with NCT01991106.
Asunto(s)
Absorciometría de Fotón , Grasa Intraabdominal/diagnóstico por imagen , Imagen por Resonancia Magnética , Obesidad Infantil/diagnóstico por imagen , Adolescente , Composición Corporal , Índice de Masa Corporal , Niño , Estudios Transversales , Femenino , Humanos , Grasa Intraabdominal/fisiopatología , Estudios Longitudinales , Masculino , Obesidad Infantil/fisiopatología , Reproducibilidad de los Resultados , Conducta de Reducción del RiesgoRESUMEN
GH plays a pivotal role in regulating body growth and development, which is modulated by sex steroids. A close interplay between estrogen and GH leads to attainment of gender-specific body composition during puberty. The physiological basis of the interaction is not well understood. Most previous studies have focused on the effects of estrogen on GH secretion. There is also strong evidence that estrogen modulates GH action independent of secretion. Oral but not transdermal administration of estrogen impairs the metabolic action of GH in the liver, causing a fall in IGF-I production and fat oxidation. This results in a loss of lean tissue and a gain of body fat in postmenopausal women and an impairment of GH effect in hypopituitary women on GH replacement. The negative metabolic sequelae are potentially important because of the widespread use of oral estrogen and estrogen-related compounds. Estrogen affects GH action at the level of receptor expression and signaling. More recently, estrogen has been shown to inhibit Janus kinase/signal transducer and activator of transcription signaling by GH via the induction of suppressor of cytokine signaling-2, a protein inhibitor for cytokine signaling. This represents a novel paradigm of steroid regulation of cytokine receptors and is likely to have significance for a diverse range of cytokine function.
Asunto(s)
Estrógenos/fisiología , Hormona del Crecimiento/fisiología , Homeostasis , Animales , Composición Corporal , Proteínas Portadoras/fisiología , Citocinas/fisiología , Estrógenos/farmacología , Estrógenos/uso terapéutico , Femenino , Crecimiento , Humanos , Factor I del Crecimiento Similar a la Insulina/fisiología , Masculino , Receptores Citoplasmáticos y Nucleares/fisiología , Receptores de Estrógenos/fisiología , Receptores de Somatotropina/fisiología , Transducción de SeñalRESUMEN
CONTEXT: Familial neurohypophyseal diabetes insipidus (FNDI) is a rare disorder resulting from arginine vasopressin (AVP) gene mutations. A partial defect in AVP secretion occurs early in the course of FNDI and may not be detected by a water deprivation test (WDT). Testing for AVP gene mutations may confirm a diagnosis of FNDI when a WDT is inconclusive and may also predict individuals who will later develop FNDI. OBJECTIVE: To test the utility of AVP gene analysis in confirming the diagnosis of FNDI. PATIENTS: Five families (20 subjects, 14 symptomatic and six asymptomatic) with FNDI and nine children with idiopathic neurohypophyseal diabetes insipidus (INDI). MEASUREMENTS: Genomic DNA was analysed for AVP gene mutations using polymerase chain reaction (PCR) amplification and sequencing. RESULTS: Heterozygous AVP gene mutations were found in all subjects with FNDI but none of the ICDI patients. Each family had their own distinct mutation. We identified two novel mutations (C44W and C105S). One asymptomatic subject developed diabetes insipidus (DI) 4 months after detection of an AVP gene mutation. The WDT suggested partial DI in 4/6 but was normal in 2/6 children with FNDI. CONCLUSION: AVP gene testing allowed diagnostic confirmation of FNDI when the WDT was inconclusive in symptomatic children, therefore obviating the need for a repeat WDT and enabling earlier initiation of appropriate treatment. AVP gene testing also has the potential to identify which asymptomatic children will later develop FNDI.