Energy dense salty food consumption frequency is associated with diastolic hypertension in Spanish children

High blood pressure (BP) is a risk factor for cardiovascular disease and sodium consumption is related to high BP. Moreover, sugar-sweetened beverages (SSB) and the Dietary Approach to Stop Hypertension (DASH) influence BP. For this reason, we investigated whether: 1) children with risk of elevated BP had a higher consumption frequency (CF) of energy-dense salty foods (EDSF), high-sugary foods (HSF) and SSB or a low DASH score; and 2) children with a higher CF of EDSF showed a worse anthropometric and metabolic profile. Anthropometry, BP and general biochemical parameters were measured in 687 Spanish children (5-16 years) with normal or excess weight. A food frequency questionnaire was used to calculate EDSF, HSF and SSB consumption, and modified DASH score. Results showed that sex and pubertal stage influenced modified DASH score. Diastolic hypertension was associated to higher CF of EDSF in the whole sample and to higher CF of SSB in pubertal children, both independently of nutritional status. In addition, CF of EDSF was positively associated with CF of HSF and SSB and inversely associated with modified DASH score. Targeted policies and intervention programs, specific for different age ranges, should be established that aim to reduce salt consumption from snacks and processed foods, which could reduce HSF and SSB consumption as well

Antioxidants and Oxidative Stress in Children: Influence of Puberty and Metabolically Unhealthy Status

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically healthy (MH) prepubertal and pubertal children and their associations with pro-inflammatory and endothelial damage biomarkers, taking puberty into account. A total of 1444 Spanish children aged 3–17 years (48.9% males, 66% prepubertal, 47.1% with obesity) were recruited. Blood pressure, anthropometric and biochemical parameters were measured, and children were categorized as having a MU or MH status according to risk factors. Retinol, carotenes, tocopherols, total antioxidant capacity (TAC), oxidized low-density lipoprotein and selected pro-inflammatory and endothelial damage biomarkers were analyzed. General linear models adjusted for age, sex, recruitment center and body mass index, partial correlations and stepwise linear regressions were performed. Lower carotenes and tocopherols levels were found in MU than in MH children. Plasma TAC was lower in prepubertal and higher in pubertal children with obesity compared to normal-weight children. Antioxidants and oxidative stress biomarkers showed novel associations with several pro-inflammatory and endothelial damage biomarkers, with pubertal differences, supporting the importance of considering both the antioxidant and oxidative stress status and puberty in the prevention of metabolic diseases in childhood.Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI051968 PI11/01425 PI1102042 PI11/02059 PI16/01301 PI16/012 PI1600871CIBEROBN Network CB12/03/30038 CB15/00131 CB15/0004

Common Variants in 22 Genes Regulate Response to Metformin Intervention in Children with Obesity: A Pharmacogenetic Study of a Randomized Controlled Trial

Metformin is a first-line oral antidiabetic agent that has shown additional effects in treating obesity and metabolic syndrome. Inter-individual variability in metformin response could be partially explained by the genetic component. Here, we aimed to test whether common genetic variants can predict the response to metformin intervention in obese children. The study was a multicenter and double-blind randomized controlled trial that was stratified according to sex and pubertal status in 160 children with obesity. Children were randomly assigned to receive either metformin (1g/d) or placebo for six months after meeting the defined inclusion criteria. We conducted a post hoc genotyping study in 124 individuals (59 placebo, 65 treated) comprising finally 231 genetic variants in candidate genes. We provide evidence for 28 common variants as promising pharmacogenetics regulators of metformin response in terms of a wide range of anthropometric and biochemical outcomes, including body mass index (BMI) Z-score, and glucose, lipid, and inflammatory traits. Although no association remained statistically significant after multiple-test correction, our findings support previously reported variants in metformin transporters or targets as well as identify novel and promising loci, such as the ADYC3 and the BDNF genes, with plausible biological relation to the metformin’s action mechanism. Trial Registration: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011 (URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023061-21/ES).This research was funded by the Spanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health Products (codes and beneficiaries: EC10-243, Ramón Cañete, Reina Sofía Hospital, Córdoba; EC10-056, Ángel Gil, University of Granada and Virgen de las Nieves University Hospital, Granada; EC10-281, Rosaura Leis, Clinic University Hospital of Santiago, Santiago de Compostela; and EC10-227, Gloria Bueno, Lozano Blesa University Clinical Hospital, Zaragoza

Cluster Analysis of Physical Activity Patterns, and Relationship with Sedentary Behavior and Healthy Lifestyles in Prepubertal Children: Genobox Cohort

Sedentary habits during childhood are associated with adverse health outcomes. The aim of this work was to cluster lifestyle behaviors and metabolic biomarkers to establish different patterns in children. Their physical and sedentary activities were evaluated by accelerometry, and questionnaires that included lifestyle behaviors, such as adherence to a Mediterranean diet, anthropometry and blood biochemical markers. Cluster analysis was performed to establish different groups based on physical activity levels. A total of 489 children were finally selected. Cluster 1 included children with a mostly sedentary state, whereas Cluster 3 included the most active children and Cluster 2 included children that did not fit into either the sedentary or the highly active groups. In Cluster 3, 56% of children were in a sports club, and a lower percentage used electronic devices in their rooms compared to the other groups. Cluster 1 children exhibited higher insulin, HOMA-IR and triacylglycerides with respect to the other groups. No differences were found regarding adherence to a Mediterranean diet. The choice to practice an extracurricular sport could be an influencing factor to increase exercise and ensure an active lifestyle in children. Reducing or limiting screen time mainly in children''s rooms could contribute to an active lifestyle

Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial

Background: Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. Methods: The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. Results: Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumptionSpanish Ministry of Health, Social and Equality, General Department for Pharmacy and Health ProductsInstituto de Salud Carlos III-Fondo de Investigación Sanitaria (FONDOS FEDER), Redes temáticas de investigación cooperativa RETIC Red SAMID RD12/0026/001

Relationship between Physical Activity, Oxidative Stress, and Total Plasma Antioxidant Capacity in Spanish Children from the GENOBOX Study

The World Health Organization has recommended performing at least 60 min a day of moderate-to-vigorous physical activity (MVPA) and reducing sedentarism in children and adolescents to offer significant health benefits and mitigate health risks. Physical fitness and sports practice seem to improve oxidative stress (OS) status during childhood. However, to our knowledge, there are no data regarding the influence of objectively-measured physical activity (PA) and sedentarism on OS status in children and adolescents. The present study aimed to evaluate the influence of moderate and vigorous PA and sedentarism on OS and plasma total antioxidant capacity (TAC) in a selected Spanish population of 216 children and adolescents from the GENOBOX study. PA (light, moderate, and vigorous) and sedentarism (i.e., sedentary time (ST)) were measured by accelerometry. A Physical Activity-Sedentarism Score (PASS) was developed integrating moderate and vigorous PA and ST levels. Urinary 8-hydroxy-20-deoxyguanosine (8-OHdG) and isoprostane F2 (F2-IsoPs), as markers of OS, were determined by ELISA; and TAC was estimated by colorimetry using an antioxidant kit. A higher PASS was associated with lower plasma TAC and urinary 8-OHdG and F2-IsoPs, showing a better redox profile. Reduced OS markers (8-OHdG and F2-IsoPs) in children with higher PASS may diminish the need of maintaining high concentrations of antioxidants in plasma during rest to achieve redox homeostasis.Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) PI11/02042 PI11/02059 PI11/01425 PI16/00871 PI16/01301 PI16/01205RETIC (Redes temáticas de investigación cooperativa) Red SAMID RD12/0026/0015Instituto de Salud Carlos III European Commission IFI17/00048Research Plan of the Vice-Rectorate of Research and Transfer of the University of Granada, Spai

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)Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563); CIBEROBN Network (CB15/00131, CB15/00043); and Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015)S

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)Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by the Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Health Research Funding (FONDOS FEDER) (PI11/01425, PI11/02042, PI11/02059, PI16/01301, PI16/01205, PI16/00871 and PI20/00563); CIBEROBN Network (CB15/00131, CB15/00043); and Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015)S

ANGPTL-4 is Associated with Obesity and Lipid Profile in Children and Adolescents

Angiopoietin-like protein 4 (ANGPTL-4) regulates lipidic metabolism and affects energy homeostasis. However, its function in children with obesity remains unknown. We investigated plasma ANGPTL-4 levels in children and its relationship with body mass index (BMI) and different lipidic parameters such as free fatty acids (FFA). Plasma ANGPTL-4 levels were analyzed in two different cohorts. In the first cohort (n = 150, age 3–17 years), which included children with normal weight or obesity, we performed a cross-sectional study. In the second cohort, which included only children with obesity (n = 20, age 5–18 years) followed up for two years after an intervention for weight loss, in which we performed a longitudinal study measuring ANGPTL-4 before and after BMI-loss. In the cross-sectional study, circulating ANGPTL-4 levels were lower in children with obesity than in those with normal weight. Moreover, ANGPTL-4 presented a negative correlation with BMI, waist circumference, weight, insulin, homeostasis model assessment of insulin resistance index (HOMA index), triglycerides, and leptin, and a positive correlation with FFA and vitamin-D. In the longitudinal study, the percent change in plasma ANGPTL-4 was correlated with the percent change in FFA, total-cholesterol and high-density lipoprotein cholesterol. This study reveals a significant association of ANGPTL-4 with pediatric obesity and plasma lipid profileThis research was funded by INSTITUTO DE SALUD CARLOS III cofounded by FEDER, grants number PI18/00998, PI15/01272, PI11/02042, PI16/01301, and PI16/00871, and FUNDACIÓN MUTUA MADRILEÑAS

Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

Fil: Melendi, Santiago E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pérez, María M. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Salas, Cintia E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Aguirre, Camila. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Baleta, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Balsano, Facundo J. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Caldano, Mariano G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Colignon, María G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Oliveira Brasil, Thayana De. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Wolodimeroff, Nicolás de. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Déramo Aquino, Andrea I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fernández de Córdova, Ana G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fontan, María B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Galvagno, Florencia I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Haedo, Mariana F. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Iturrieta Araya, Noelia S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Mollinedo Cruz,Volga S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Olivero, Agustín. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pestalardo, Ignacio. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ricciardi, María. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Saltos Navarrete, Jandry D. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Vera Rueda, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Villaverde, María C. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Xavier, Franco B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Lauko, Marcela. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ujeda, Carlos. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Leis, Rocío. Hospital General de Agudos Carlos G. Durand; Argentina.INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica