El ácido úrico se asocia con características de un síndrome de resistencia insulínica en los niños obesos en etapas perdurables

Elevated plasma uric acid levels are associated with obesity and could be an expression of insulin-resistant state. The aim of the present study was to evaluate plasma uric acid in obese and normal-weight children exclusively at prepubertal stage and its relationship with anthropometric measurements, intake, and features of the insulin resistance syndrome. A study was performed in 34 obese and 20 normal- weight prepubertal children. Nutrient intake was determined using a 72 h recall questionnaire and a consumption food frequency questionnaire. Anthropometric parameters and fasting plasma lipids, glucose, insulin, leptin, adiponectin, tumour necrosis factor (TNF-α) and uric acid were measured. Multiple regression analysis was used to identify association of anthropometric parameters, nutrient intake and insulin resistance syndrome variables (arterial blood pressure, plasma glucose, insulin, homeostasis model assessment of insulin resistance index- HOMA- triacylglycerols and, HDL-cholesterol) with uric acid. Plasma uric concentration was significantly higher in the obese group than in the control group and when adjusted by sex, age and BMI was positively associated with tricipital skinfold and insulin resistance, and negatively with adiponectin. In multiple regression analysis, BMI, HDL-cholesterol and adiponectin were independent predictors of plasma uric acid. In conclusion, elevated levels of uric acid in obese children, compared with lean subjects, at the prepubertal period, seems to be an early metabolic alteration that is associated with other features of insulin resistance syndrome.Los niveles elevados de ácido úrico plasmáticos se asocian a la obesidad y pueden ser la expresión de un estado de resistencia insulínica. El objetivo de este estudio ha sido evaluar la concentración plasmática de ácido úrico en niños obesos y normales, exclusivamente en edad prepuberal, y determinar su relación con las medidas antropométricas, la ingesta dietética y los parámetros asociados al síndrome de resistencia insulínica. El estudio se llevó a cabo en 34 niños obesos y 20 controles en edad prepuberal a los cuales se les estimó su ingesta dietética mediante el registro de un cuestionario de ingesta de alimentos de 72 h y un cuestionario de frecuencia de consumo de alimentos y se determinaron, además de los parámetros antropométricos, la glucosa, la insulina, la leptina, la adiponectina y el factor de necrosis tumoral alfa (TNF-α) plasmáticos. Se realizó un análisis de regresión múltiple para identificar la asociación entre los niveles de ácido úrico y los parámetros antropométricos, la ingesta de nutrientes y las variables clásicas relacionadas con el síndrome de resistencia insulínica (hipertensión, glucosa, insulina, índice de resistencia insulínica HOMA, triglicéridos y HDL-colesterol plasmáticos), así como con leptina, adiponectina y TNF-α. La concentración plasmática de ácido úrico fue significativamente más elevada en los niños obesos que en los controles y, cuando se ajustó por sexo, edad e índice de masa corporal, los niveles de ácido úrico se asociaron con el pliegue tricipital y la resistencia inulínica, y negativamente con la adiponectina. En el análisis de regresión múltiple, el índice de masa corporal, el HDL-colesterol y la adiponectina fueron predictores independientes del ácido úrico plasmático. En conclusión, los niveles elevados de ácido úrico en niños obesos en edad prepuberal, comparado con los de los niños normales, representan una alteración metabólica temprana asociada con la resistencia insulínica.This work was supported by the Spanish Ministry of Health and Consumer Affairs, the Spanish National Program for Scientific Research, Development, and Technological Innovation (I+D+I), and the Instituto de Salud Carlos III (Spanish National Health Research Institute), FEDER co-financed Project No. PI 051968. Mercedes Gil-Campos was a research scientist appointed on a training contract funded by the Carlos III Health Research Institute

Commentary: Consumer Reports of "Keto Flu" Associated With the Ketogenic Diet

CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN) Consorcio Centro de Investigación Biomédica en Red, M.P. (CIBER) Instituto de Salud Carlos II

Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases

The pediatric population is continually at risk of developing infectious and inflammatory diseases. The treatment for infections, particularly gastrointestinal conditions, focuses on oral or intravenous rehydration, nutritional support and, in certain case, antibiotics. Over the past decade, the probiotics and synbiotics administration for the prevention and treatment of different acute and chronic infectious diseases has dramatically increased. Probiotic microorganisms are primarily used as treatments because they can stimulate changes in the intestinal microbial ecosystem and improve the immunological status of the host. The beneficial impact of probiotics is mediated by different mechanisms. These mechanisms include the probiotics’ capacity to increase the intestinal barrier function, to prevent bacterial transferation and to modulate inflammation through immune receptor cascade signaling, as well as their ability to regulate the expression of selected host intestinal genes. Nevertheless, with respect to pediatric intestinal diseases, information pertaining to these key mechanisms of action is scarce, particularly for immune-mediated mechanisms of action. In the present work, we review the biochemical and molecular mechanisms of action of probiotics and synbiotics that affect the immune system.Julio Plaza-Diaz, Francisco Javier Ruiz-Ojeda and Angel Gil are part of University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES)

Neurodegeneation treatment in lysosomal diseases. An update

Las enfermedades lisosomales son un conjunto de enfermedades raras donde el déficit genético de determinadas enzimas da lugar a la acumulación de sustratos a nivel multiorgánico. El tratamiento de estos errores innatos del metabolismo sigue en continua investigación puesto que cuando existen, presentan limitaciones tratando de aumentar la síntesis de la enzima o disminuir el depósito de sustrato, sin llegar a la solución definitiva y, por tanto, a la curación. La neurodegeneración progresiva y limitante que la mayor parte de ellas producen desde edades pediátricas, supone uno de los mayores desafíos. El trasplante de células hematopoyéticas y la terapia de reemplazo enzimático son tratamientos aceptados para algunas de estas enfermedades; sin embargo, sus resultados sobre el control y la progresión de la sintomatología neurológicas en muchas ocasiones siguen siendo desalentadores. Sin duda, atravesar la barrera hematoencefálica es uno de los obstáculos que numerosos ensayos clínicos, que se están desarrollando en la actualidad, pretenden solventar. La terapia génica y aquella sobre las vías neurofisiológicas desencadenadas por la falta de degradación parcial o total de moléculas constituyen una nueva vía de estudio cuyo objetivo principal también se basa en evitar la progresión en el deterioro de la función cognitiva. Por tanto, el objetivo de este trabajo es realizar una revisión para conocer las terapias aprobadas y las líneas de investigación en curso en relación a la neurodegeneración de las enfermedades lisosomales. Es fundamental seguir avanzando en este campo con mayor desarrollo de estos enfoques y la búsqueda de nuevas perspectivas en las terapias que pueden suponer un gran impacto en la calidad de vida de estos pacientes.Lysosomal diseases are a set of rare diseases where the genetic deficiency of certain enzymes gives rise to the accumulation of substrates at the multi-organ level. The treatment of these inborn errors of metabolism is still under continuous investigation since when they exist, they present limitations trying to increase the synthesis of the enzyme or decrease the deposit of substrate, without reaching the definitive solution, and therefore a cure. The progressive and limiting neurodegeneration that most of them produce from pediatric ages, is one of the greatest challenges. Hematopoietic cell transplantation and enzyme replacement therapy are accepted treatments for some of these diseases; however,its results on the control and progression of neurological symptoms often remain disappointing. Undoubtedly, crossing the blood-brain barrier is one of the obstacles that many clinical trials currently underway aim to overcome. Gene therapy and neurophysiological pathways triggered by the lack of partial or total degradation of molecules also constitute a new avenue of study whose main objective is also based on preventing progression in the deterioration of cognitive function. Therefore, the objective of this work is to carry out a review to know the approved therapies and the lines of research in progress in relation to the neurodegeneration of lysosomal diseases and It is essential to continue advancing in this field with further development of these approaches and the search new perspectives on therapies that can have a great impact on the quality of life of these patients

Longitudinal associations between cardiovascular biomarkers and metabolic syndrome during puberty: the PUBMEP study

Puberty has been described as a life stage of considerable metabolic risk specially for those with obesity. The low-grade systemic inflammatory status associated with obesity could be one of the connections with metabolic syndrome (MetS). Thus, we aimed to assess the relationship between inflammatory and cardiovascular biomarkers and the development of MetS during puberty. Seventy-five children from the PUBMEP study (33 females), aged 4–18 years, were included. Cardiovascular and inflammatory biomarkers were measured in the prepubertal and pubertal stage, including high-sensitivity C-reactive protein (CRP), leptin, tumor necrosis factor-alpha (TNFα), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP-1), total plasminogen activator inhibitor-1 (tPAI), resistin, adiponectin, myeloperoxidase (MPO), and soluble intercellular adhesion molecule-1 (sICAM-1). MetS was diagnosed at each measurement point. Mixed-effects and logistic regressions were performed. Those children with MetS in puberty presented higher prepubertal values of several cardiometabolic biomarkers in comparison to those without MetS (z-score body mass index (zBMI), waist circumference, insulin, HOMA-IR, leptin, and tPAI (p < 0.05)). For prepubertal children with obesity, the odds of developing MetS in puberty were significantly higher in those having high zBMI (OR = 4.27; CI: 1.39–22.59) or high concentrations of tPAI (OR = 1.19; CI: 1.06–1.43). Conclusion: Those with obesity with higher prepubertal tPAI plasma levels had 19% higher odds of having MetS at puberty highlighting the existence of association between MetS, obesity, and inflammation already in puberty. Thus, assessing cardiometabolic and inflammatory status in children with obesity already at prepuberty is key to avoiding future comorbidities.CRUE-CSIC agreementSpringer NaturePlan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research PI11/01425 PI11/02042 PI11/02059 PI16/01301 PI16/01205 PI16/00871 PI20/00563CIBEROBN Network CB15/00131 CB15/00043Redes tematicas de investigacion cooperativa RETIC Red SAMID RD12/0026/001

Effects of Dairy Product Consumption on Height and BoneMineral Content in Children: A Systematic Review of Controlled Trials

There is a physiological basis for the roles of selected nutrients, especially proteins, calcium, and vitamin D, in growth and development, which are at a maximum during the pediatric period. Milk and dairy products are particularly rich in this group of nutrients. The present systematic review summarizes the available evidence relating dairy product intake with linear growth and bone mineral content in childhood and adolescence. A search was conducted in the MEDLINE (via PubMed) and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines and included intervention-controlled clinical trials with dairy products in children from 1 January, 1926 to 30 June, 2018. The risk of bias for each study was assessed using the Cochrane methodology. The number of study participants, the type of study and doses, the major outcomes, and the key results of the 13 articles included in the review are reported. The present systematic review shows that supplementing the usual diet with dairy products significantly increases bone mineral content during childhood. However, the results regarding a possible relation between dairy product consumption and linear growth are inconclusive.This study was partially funded by the University of Granada Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and Health (UCEES), Plan Propio de Investigación 2018, Programa Contratos-Puente, the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades, and European Regional Development Funds (ref. SOMM17/6107/UGR)

Evaluation of Physical Activity and Lifestyle Interventions Focused on School Children with Obesity Using Accelerometry: A Systematic Review and Meta-Analysis

Despite the existence of global recommendations for physical activity and lifestyle to avoid childhood obesity, there are no specific recommendations for school-age children. The aim of this meta-analysis was to measure the effects of current interventions with a physical activity component on body mass index (BMI) Z-score and on the moderate and vigorous physical activity (MVPA) time, measured by accelerometry, and focused on children with obesity. Randomized controlled trial studies (RCTs) based on physical activity interventions focused on children with obesity (6 to 12 years old) from January 1991 to August 2018 were included. The post-intervention mean and standard deviation of the BMI Z-score and MVPA engaged time were extracted to calculate the results using random effects models. Of a total of 229 studies considered potentially eligible, only 10 RCTs met the inclusion criteria. There were improvements in the BMI Z-score for physical activity intervention groups, compared with non-intervention children in addition to a significant increase in time engaged in MVPA. In conclusion, interventions with a physical activity component in school-children with obesity seem to be effective at reducing BMI and producing an increase in time spent engaged in physical activity. Therefore, interventions based on physical activity should be considered one of the main strategies in treating childhood obesity

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance.This work was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (PI020826, PI051968, PI1102042, and PI1600871), RETIC (Red SAMID RD12/0026/0015) and Fondo Europeo De Desarrollo Regional (FEDER)

Influencia de la fuerza muscular isométrica de las extremidades superiores en el estrés oxidativo en niños. (Influence of handgrip strength in oxidative stress in children).

<b>Resumen</b><p align="justify">El ejercicio físico puede producir estrés oxidativo en el individuo lo que pueden condicionar el riesgo cardiovascular en niños y adolescentes. Este estudio pretende analizar el estrés oxidativo según la fuerza muscular isométrica de las extremidades superiores en la edad pediátrica. Se estudiaron 70 niños sanos con edades entre 10 y 14 años, y se analizaron en saliva los lipoperóxidos (LPO), el glutatión reducido (GSH), la ratio GSH/LPO y la catalasa, como marcadores de estrés oxidativo. La muestra se dividió en dos grupos según una condición física superior o inferior medida a través de dinamometría manual (TKK 5110); se diferenció la serie en sujetos prepuberales y puberales. Se encontraron niveles significativamente inferiores de GSH y GSH/LPO en el grupo de niños con fuerza superior, y en los puberales con la mismas características; estos resultados podrían indicar la existencia de un mayor estrés oxidativo en esta situación. En conclusión, los mayores niveles de fuerza músculo esquelética, medida a través de dinamometría manual, posiblemente pueden estar asociados a un mayor estrés oxidativo en niños púberes con condición física musculoesquelética superior.</p><b>Abstract</b><p align="justify">Physical exercise can produce oxidative stress, this situation could contribute cardiovascular risk in children and adolescents. The following study tries to evaluate the oxidative stress produced according to the handgrip strength in infancy. 70 healthy male subjects, ages 10 to 14 years, were studied. In the saliva samples, lipoperoxides (LPO), reduced glutathione (GSH), glutathione/lipoperoxides ratio and catalase were analyzed as biomarkers of oxidative stress. Children were divided into two groups according to their handgrip strength (high or low) measured by handgrip strength (TKK 5110). The groups were also divided into prepubertal and pubertal subjects. We found GSH’s significantly low levels and of GSH/LPO in pubertal group with high handgrip strength. We could possibly conclude that the higher levels of handgrip strength could be associated with more oxidative stress in pubertal group with high fitness.</p>doi:10.5232/ricyde2011.0220

Influence of handgrip strength in oxidative stress in children

El ejercicio físico puede producir estrés oxidativo en el individuo lo que pueden condicionar el riesgo cardiovascular en niños y adolescentes. Este estudio pretende analizar el estrés oxidativo según la fuerza muscular isométrica de las extremidades superiores en la edad pediátrica. Se estudiaron 70 niños sanos con edades entre 10 y 14 años, y se analizaron en saliva los lipoperóxidos (LPO), el glutatión reducido (GSH), la ratio GSH/LPO y la catalasa, como marcadores de estrés oxidativo. La muestra se dividió en dos grupos según una condición física superior o inferior medida a través de dinamometría manual (TKK 5110); se diferenció la serie en sujetos prepuberales y puberales. Se encontraron niveles significativamente inferiores de GSH y GSH/LPO en el grupo de niños con fuerza superior, y en los puberales con la mismas características; estos resultados podrían indicar la existencia de un mayor estrés oxidativo en esta situación. En conclusión, los mayores niveles de fuerza músculo esquelética, medida a través de dinamometría manual, posiblemente pueden estar asociados a un mayor estrés oxidativo en niños púberes con condición física musculoesquelética superior.Physical exercise can produce oxidative stress, this situation could contribute cardiovascular risk in children and adolescents. The following study tries to evaluate the oxidative stress produced according to the handgrip strength in infancy. 70 healthy male subjects, ages 10 to 14 years, were studied. In the saliva samples, lipoperoxides (LPO), reduced glutathione (GSH), glutathione/lipoperoxides ratio and catalase were analyzed as biomarkers of oxidative stress. Children were divided into two groups according to their handgrip strength (high or low) measured by handgrip strength (TKK 5110). The groups were also divided into prepubertal and pubertal subjects. We found GSH’s significantly low levels and of GSH/LPO in pubertal group with high handgrip strength. We could possibly conclude that the higher levels of handgrip strength could be associated with more oxidative stress in pubertal group with high fitness