Psychometric analysis of the cross-cultural Spanish version of the diabetes management questionnaire.

Evaluation of the degree of adherence to self-care among Spanish type 1 diabetes (T1DM) pediatric population lacks of a validated tool. PURPOSE: To cross-culturally adapt and determine the psychometric properties of the Spanish version of the Diabetes Management Questionnaire to assess the degree of adherence to self-care among children with T1DM. METHODS: Translation, back-translation, and patient suggestions, were considered to obtain the Spanish version (DMQ-Sp). A cross-sectional study was conducted with 323 children (aged 8-18 years) with T1DM and their parents to determine internal reliability, structural validity, and external validity. Responsiveness to change was analyzed through a prospective longitudinal study involving 102 newly diagnosed T1DM patients. Psychometrics were evaluated for the entire sample and stratified by age (8-12 and 13-18 years). RESULTS: A total of 323 children with T1DM [49.8% female; age 13.3 ± 2.8 years; 155 aged 8-12; glycated hemoglobin (HbA1c) value 7.7 ± 1.0%] answered the Spanish final version. The internal consistency Cronbach's alpha was 0.76 and intraclass correlation coefficient 0.84. Test-retest reliability was r = 0.84 (p < 0.001). Fit index of structural validity was >0.7. External validity correlated inversely with HbA1c (r = -0.39; p < 0.001). The DMQ-Sp score increased significantly after 6 months of receiving the full therapeutic education program (TEP) (baseline 57.07 ± 10.81 vs. 6 months 78.80 ± 10.31; p < 0.001). CONCLUSION: The DMQ-Sp is reliable, valid, and sensitive to change in a large sample of children (aged 8-18 years) with T1DM and their parents. PRACTICE IMPLICATIONS: DMQ-Sp can be a useful tool for diabetes teams to identify adherence to different tasks and to evaluate TEPs.

Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.

Postnatal overfeeding increases the risk of chronic diseases later in life, including obesity, insulin resistance, hepatic steatosis, and type 2 diabetes. Epigenetic mechanisms might underlie the long-lasting effects associated with early nutrition. Here we aimed to explore the molecular pathways involved in early development of insulin resistance and hepatic steatosis, and we examined the potential contribution of DNA methylation and histone modifications to long-term programming of metabolic disease. We used a well-characterized mouse model of neonatal overfeeding and early adiposity by litter size reduction. Neonatal overfeeding led to hepatic insulin resistance very early in life that persisted throughout adulthood despite normalizing food intake. Up-regulation of monoacylglycerol O-acyltransferase ( Mogat) 1 conceivably mediates hepatic steatosis and insulin resistance through increasing intracellular diacylglycerol content. Early and sustained deregulation of Mogat1 was associated with a combination of histone modifications that might favor Mogat1 expression. In sum, postnatal overfeeding causes extremely rapid derangements of hepatic insulin sensitivity that remain relatively stable until adulthood. Epigenetic mechanisms, particularly histone modifications, could contribute to such long-lasting effects. Our data suggest that targeting hepatic monoacylglycerol acyltransferase activity during early life might provide a novel strategy to improve hepatic insulin sensitivity and prevent late-onset insulin resistance and fatty liver disease.-Ramon-Krauel, M., Pentinat, T., Bloks, V. W., Cebrià, J., Ribo, S., Pérez-Wienese, R., Vilà, M., Palacios-Marin, I., Fernández-Pérez, A., Vallejo, M., Téllez, N., Rodríguez, M. À., Yanes, O., Lerin, C., Díaz, R., Plosch, T., Tietge, U. J. F., Jimenez-Chillaron, J. C. Epigenetic programming at the Mogat1 locus may link neonatal overnutrition with long-term hepatic steatosis and insulin resistance.

eRah: A Computational Tool Integrating Spectral Deconvolution and Alignment with Quantification and Identification of Metabolites in GC/MS-Based Metabolomics.

Gas chromatography coupled to mass spectrometry (GC/MS) has been a long-standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ionization (EI). However, the use of GC-EI MS in untargeted metabolomics produces large and complex data sets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information on metabolites across multiple biological samples, integrated computational workflows for data processing are needed. Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC/MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), (iii) alignment of mass spectra across samples, (iv) missing compound recovery, and (v) identification of metabolites by spectral library matching using publicly available mass spectra. eRah outputs a table with compound names, matching scores and the integrated area of compounds for each sample. The automated capabilities of eRah are demonstrated by the analysis of GC-time-of-flight (TOF) MS data from plasma samples of adolescents with hyperinsulinaemic androgen excess and healthy controls. The quantitative results of eRah are compared to centWave, the peak-picking algorithm implemented in the widely used XCMS package, MetAlign, and ChromaTOF software. Significantly dysregulated metabolites are further validated using pure standards and targeted analysis by GC-triple quadrupole (QqQ) MS, LC-QqQ, and NMR. eRah is freely available at http://CRAN.R-project.org/package=erah .

Instability of glucose values in very preterm babies at term postmenstrual age.

OBJECTIVE: To determine if very preterm (VPT) babies are capable of maintaining glucose levels within normal ranges at or near term postmenstrual age. STUDY DESIGN: Glucose levels were intermittently or continuously monitored during 48 hours in a cohort of 60 VPT infants near hospital discharge. Hypoglycemic (≤45 mg/dL, 2.5 mmol/L) and hyperglycemic (≥140 mg/dL or 7.8 mmol/L, severe if ≥180 mg/dL or 10 mmol/L) episodes were considered relevant if they lasted longer than 30 minutes. Feeding regimes followed current practice. RESULTS: With intermittent capillary, 2 hypoglycemic values and another 3 that were abnormally high were detected. With continuous monitoring, 6 babies (10.0%) had isolated hypoglycemia ≤45 mg/dL (2.5 mmol/L) (3 of them reaching 40 mg/dL, 2.2 mmol/L), 14 (23.3%) had isolated hyperglycemia, and 8 (13.3%) had episodes of both. The mean duration of hypoglycemia per patient was 2.8 ± 2.9 hours and 4.68 ± 4.35 hours in the case of hyperglycemia, with 12 infants becoming severely hyperglycemic. Of the 12 severely hyperglycemic patients, 5 also developed severe hypoglycemia. No specific characteristics identified the hypoglycemic babies. A history of intrauterine growth restriction (P = .037) and female sex (P = .063) seemed to increase the risk of severe hyperglycemia. CONCLUSIONS: VPT infants continue to have abnormal glucose values, especially hyperglycemia, by the time of hospital discharge. No specific factors identify babies at higher risk for hypoglycemia, and intrauterine growth restriction and female sex seemed to predispose to hyperglycemia.

Influence of socioeconomic factors on glycemic control, therapeutic adherence and quality of life in children and adolescents with type 1 diabetes.

OBJECTIVE: To stablish the relationship between socioeconomic status of a cohort of children and adolescents with type 1 diabetes (T1D) with glycemic control, therapeutic adherence and diabetes quality of life (DQoL). PATIENTS Y METHODS: A cross-sectional, observational study with consecutive inclusion was carried out. Participants aged 8-18 years with T1D duration >1 year. Data on family structure, family income, parents' educational level and parental role on primary diabetes care supervision were registered. Adherence (DMQ-Sp) and DQoL (PedsQl) were analyzed. Linear and logistic regression models adjusted for demographics, family structure and parental role on primary diabetes care responsibility were applied. RESULTS: A total of 323 patients (T1D duration 5,3 ±â€¯3,3 years; HbA1c 7,7 ±â€¯1,0%; age 13,3 ±â€¯2,8 years; 49,8% females) were included. Patients living in a nuclear family and those whose main diabetes care supervision was shared by both parents showed lower HbA1c [adjusted for demographics and family structure (7,06; CI 95% 6,52-7,59); adjusted for demographics and role on primary diabetes care supervision (7,43; CI 95% 6,57-8,28)]. DMQ-Sp score (adjusted for demographics and role on main supervision) was higher in patients whose parents shared the diabetes care supervision (84,56; CI 95% 73,93-95,19). Parents sharing diabetes care supervision showed a significantly higher PedsQl score (both 74,63 ±â€¯12,70 vs mother 68,53 ±â€¯14,59; p = 0,001). CONCLUSIONS: Children and adolescents with T1D had lower HbA1c, better therapeutic adherence and better DQoL when lived in a nuclear family, with higher socioeconomic status and the responsibility for supervising diabetes care was shared by both parents.

Frequency and Predictive Factors of Hypoglycemia in Patients Treated With rhIGF-1: Data From the Eu-IGFD Registry.

CONTEXT: The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD). OBJECTIVE: This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1. METHODS: Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor. RESULTS: In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01. CONCLUSION: Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.

Attitudes, Behaviors, and Barriers among Adolescents Living with Obesity, Caregivers, and Healthcare Professionals in Spain: ACTION Teens Survey Study.

Although the prevalence of pediatric obesity is rising, understanding of the perceptions, attitudes, behaviors, and barriers to effective obesity care among Spanish adolescents living with obesity (ALwO), their caregivers, and healthcare professionals (HCPs) is lacking. In 2021, the cross-sectional ACTION Teens survey study was conducted in 10 countries; results from the Spanish cohort are presented herein. The survey was completed by 648 ALwO, 644 caregivers, and 251 HCPs in Spain. A total of 25% of ALwO and 43% of caregivers thought that their/their child's weight was normal, and more caregivers than ALwO perceived the ALwO's health to be at least good (95% vs. 59%, respectively). Only 53% of ALwO and 9% of caregivers reported receiving an obesity diagnosis, despite HCPs reporting they provide diagnoses to 87% of ALwO/caregivers. Although 65% of HCPs felt that ALwO may not be comfortable discussing weight, only 26% of ALwO who had discussed weight with an HCP (n = 488) reported not feeling comfortable. Inability to control hunger was a key barrier to ALwO losing weight identified by ALwO/caregivers, but not HCPs. Improved communication between the three groups, a better understanding of barriers to weight loss, and improved health education on obesity are needed in order to enhance obesity care in Spain.

Intergenerational Inheritance of Hepatic Steatosis in a Mouse Model of Childhood Obesity: Potential Involvement of Germ-Line microRNAs.

Childhood obesity increases the risk of developing metabolic syndrome later in life. Moreover, metabolic dysfunction may be inherited into the following generation through non-genomic mechanisms, with epigenetics as a plausible candidate. The pathways involved in the development of metabolic dysfunction across generations in the context of childhood obesity remain largely unexplored. We have developed a mouse model of early adiposity by reducing litter size at birth (small litter group, SL: 4 pups/dam; control group, C: 8 pups/dam). Mice raised in small litters (SL) developed obesity, insulin resistance and hepatic steatosis with aging. Strikingly, the offspring of SL males (SL-F1) also developed hepatic steatosis. Paternal transmission of an environmentally induced phenotype strongly suggests epigenetic inheritance. We analyzed the hepatic transcriptome in C-F1 and SL-F1 mice to identify pathways involved in the development of hepatic steatosis. We found that the circadian rhythm and lipid metabolic process were the ontologies with highest significance in the liver of SL-F1 mice. We explored whether DNA methylation and small non-coding RNAs might be involved in mediating intergenerational effects. Sperm DNA methylation was largely altered in SL mice. However, these changes did not correlate with the hepatic transcriptome. Next, we analyzed small non-coding RNA content in the testes of mice from the parental generation. Two miRNAs (miR-457 and miR-201) appeared differentially expressed in the testes of SL-F0 mice. They are known to be expressed in mature spermatozoa, but not in oocytes nor early embryos, and they may regulate the transcription of lipogenic genes, but not clock genes, in hepatocytes. Hence, they are strong candidates to mediate the inheritance of adult hepatic steatosis in our murine model. In conclusion, litter size reduction leads to intergenerational effects through non-genomic mechanisms. In our model, DNA methylation does not seem to play a role on the circadian rhythm nor lipid genes. However, at least two paternal miRNAs might influence the expression of a few lipid-related genes in the first-generation offspring, F1.

Influence of Executive Function Training on BMI, Food Choice, and Cognition in Children with Obesity: Results from the TOuCH Study.

BACKGROUND: Children with obesity have a higher risk of future health and psychological problems. Executive functions (EFs) play a key role in successful dietetic and exercise planning; therefore, new treatments aimed at improving EFs may optimize outcomes. OBJECTIVES: This study evaluates the impact of EF training on body mass index (BMI), food choice, and cognition in children with obesity. We also examine their real-life executive functioning, emotional state, and quality of life. METHODS: Randomized controlled double-blind trial. Forty-six children with obesity were randomly allocated into an executive functions training or a control task training group and attended 30-45 min of daily training (5/week over 6 weeks), with both groups receiving counseling on diet and wearing an activity/sleep tracker. Participants were evaluated at baseline and after treatment. RESULTS: BMI decreased over time in the whole sample, although there were no differences between groups at post-training in BMI, food choice, and cognition. Both groups showed significant improvements in attention, speed, cognitive flexibility, and inhibitory control. Additionally, there were some benefits in real-life executive functioning and self-esteem. Over the 6 weeks, participants showed worse food choices in both groups. CONCLUSIONS: EFs training showed a lack of significant effects. The executive function enhancement alone did not explain these changes, as there were no significant differences between the experimental groups. It might be that the control task training could also produce some benefits, and multi-component interventions might be useful for weight loss.

A time-restricted feeding intervention in children and adolescents with obesity: The TRansForm study protocol.

Obesity during childhood is of special concern as adiposity is typically tracked into adult life and it constitutes a major risk factor for future obesity and associated metabolic disorders. Recent studies indicate that time-restricted feeding (TRF) interventions may provide a promising strategy for obesity treatment. However, TRF interventions have only been tested in adult subjects. This study aims to determine both short- and long-term effects of a TRF intervention in children and adolescents with obesity. We will also investigate potential mechanisms mediating the response to the intervention, including the circadian rhythm and the gut microbiota composition. We have designed a randomized-controlled parallel-group clinical study in which children and adolescents (age range 8-18 year-old) with obesity will be subjected to time-restricted eating or no time restrictions for 2 months. Follow-up visits will allow for long-term effect assessments. We will measure anthropometric (BMI, body composition) and metabolic parameters (glucose and lipid metabolism), indicators of the circadian rhythm, and gut microbiota composition will be analyzed. This study will (1) determine safety and effectiveness of the TRF intervention in children and adolescents; (2) assess its long-term effects; and (3) evaluate potential mechanisms involved in the response to the intervention. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT05174871].

Targeting the Gut Microbiome in Prader-Willi Syndrome.

Overwhelming evidence demonstrates an important role of the gut microbiome in the development of a wide range of diseases, including obesity, metabolic disorders, and mental health symptoms. Indeed, interventions targeting the gut microbiome are being actively investigated as a therapeutic strategy to tackle these diseases. Given that obesity and mental health symptoms are both hallmarks of Prader-Willi syndrome, targeting the gut microbiome may be a promising therapeutical strategy. Only a few studies have investigated the gut microbiome in the context of Prader-Willi syndrome and assessed the efficacy of probiotic supplementation as a therapeutic strategy for this disease. Here, we review the knowledge obtained to this date regarding the gut microbiome in individuals with Prader-Willi syndrome. The limited evidence available indicate that probiotic supplementation improves some metabolic and mental health aspects, however further studies are warranted to determine whether targeting the gut microbiome may constitute a safe and efficient strategy to treat individuals with Prader-Willi syndrome.

Time-Restricted Feeding during Puberty Ameliorates Adiposity and Prevents Hepatic Steatosis in a Mouse Model of Childhood Obesity.

BACKGROUND: Time restricted feeding (TRF) refers to dietary interventions in which food access is limited during a specific timeframe of the day. TRFs have proven useful in improving metabolic health in adult subjects with obesity. Their beneficial effects are mediated, in part, through modulating the circadian rhythm. Nevertheless, the translation of these dietary interventions onto obese/overweight children and adolescents remains uncharacterized. The objective of this study is to explore the feasibility of temporal dietary interventions for improving metabolic health in the context of childhood obesity. METHODS: We have previously developed a mouse model of early adiposity (i.e., childhood obesity) through litter size reduction. Mice raised in small litters (SL) became obese as early as by two weeks of age, and as adults, they developed several obesity-related co-morbidities, including insulin resistance, glucose intolerance and hepatic steatosis. Here, we explored whether two independent short-term chrono-nutritional interventions might improve metabolic health in 1-month-old pre-pubertal SL mice. Both TRFs comprised 8 h feeding/14 h fasting. In the first one (TRF1) Control and SL mice had access to the diet for 8 h during the dark phase. In the second intervention (TRF2) food was available during the light:dark transitions. RESULTS: TRF1 did not alter food intake nor ameliorate adiposity in SL-TRF1. In contrast, SL-TRF2 mice showed unintentional reduction of caloric intake, which was accompanied by reduced total body weight and adiposity. Strikingly, hepatic triglyceride content was completely normalized in SL-TRF1 and SL-TRF2 mice, when compared to the ad lib-fed SL mice. These effects were partially mediated by (i) clock-dependent signals, which might modulate the expression of Pparg or Cpt1a, and (ii) clock-independent signals, such as fasting itself, which could influence Fasn expression. CONCLUSIONS: Time-restricted feeding is an effective and feasible nutritional intervention to improve metabolic health, namely hepatic steatosis, in a model of childhood obesity. These data open new avenues for future safe and efficient chrono-nutritional interventions aimed to improve metabolic health in children with overweight/obesity.

Executive Function Training in Childhood Obesity: Food Choice, Quality of Life, and Brain Connectivity (TOuCH): A Randomized Control Trial Protocol.

Background: Individuals with obesity are known to present cognitive deficits, especially in executive functions. Executive functions play an important role in health and success throughout the whole life and have been related to food decision-making and to the ability to maintain energy balance. It is possible to improve executive functions through targeted training. This would involve brain plasticity changes that could be studied through connectivity MRI. The general hypothesis of this study is that executive functions training in children with obesity can improve food choices and produce cognitive and neuroimaging changes (structural and functional connectivity), as well as improve emotional state and quality of life. Methods: Randomized controlled double-blind trial with 12-month follow-up. Thirty children with obesity will be randomly allocated into "executive training" (Cognifit with adaptive difficulty + Cogmed) or "control task" group (Cognifit without adaptive difficulty). Both groups will attend 30-45 min of individual gamified training (Cogmed and/or Cognifit systems) by iPad, five times per week during 6 weeks. Cogmed and Cognifit software are commercially available from Pearson and Cognifit, respectively. Participants will receive an iPad with both apps installed for a 6-week use. Participants will also receive counseling diet information via presentations sent to the iPad and will wear a Fitbit Flex 2 tracker to monitor daily activity and sleep patterns. Main outcomes will be cognitive, emotional, food decision, and quality-of-life measures, as well as neuroimaging measures. Participants are evaluated at baseline (T0), after treatment (T1), and 12 months since baseline (T2). Discussion: Longitudinal study with active control group and 3 time points: baseline, immediately after treatment, and 1 year after baseline. Threefold treatment: executive function training, psychoeducation, and feedback on activity/sleep tracking. We will evaluate the transfer effects of the intervention, including emotional and functional outcomes, as well as the effects on neural plasticity by connectivity MRI. Trial registration: This project has been registered in ClinicalTrials.gov (trial registration number NCT03615274), August 3, 2018.

Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity.

BACKGROUND: Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production. AIM: The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children. METHODS: We determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels. RESULTS: Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= - 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children. CONCLUSIONS: Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.

Neonatal overfeeding during lactation rapidly and permanently misaligns the hepatic circadian rhythm and programmes adult NAFLD.

Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. OBJECTIVE: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. METHODS: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. RESULTS: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1-3 and cryptochrome 1-2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4-6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better re-alignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). CONCLUSIONS: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially re-aligning the peripheral circadian rhythm.

Increasing breast milk betaine modulates Akkermansia abundance in mammalian neonates and improves long-term metabolic health.

Accelerated postnatal growth is a potentially modifiable risk factor for future obesity. To study how specific breast milk components contribute to early growth and obesity risk, we quantified one-carbon metabolism-related metabolites in human breast milk and found an inverse association between milk betaine content and infant growth. This association was replicated in an independent and geographically distinct cohort. To determine the potential role of milk betaine in modulating offspring obesity risk, we performed maternal betaine supplementation experiments in mice. Higher betaine intake during lactation increased milk betaine content in dams and led to lower adiposity and improved glucose homeostasis throughout adulthood in mouse offspring. These effects were accompanied by a transient increase in Akkermansia spp. abundance in the gut during early life and a long-lasting increase in intestinal goblet cell number. The link between breast milk betaine and Akkermansia abundance in the gut was also observed in humans, as infants exposed to higher milk betaine content during breastfeeding showed higher fecal Akkermansia muciniphila abundance. Furthermore, administration of A. muciniphila to mouse pups during the lactation period partially replicated the effects of maternal breast milk betaine, including increased intestinal goblet cell number, lower adiposity, and improved glucose homeostasis during adulthood. These data demonstrate a link between breast milk betaine content and long-term metabolic health of offspring.

[Cardiovascular Health School Program (PESCA). Methodology and initial results: 2018-2020]. / Programa Escolar de Salud Cardiovascular (PESCA). Metodología y primeros resultados: 2018-2020.

INTRODUCTION: Introduction: despite the fact that 40 % of children in Spain, ages 6 to 9, are overweight or obese, and 2/3 of them are at risk of developing cardiovascular disease, there is a lack of protocolized efficient interventions to fight this important health problem. The PESCA project aims to reduce the prevalence of overweight and obesity with a transversal model focused on a school intervention, but also involving families and primary care doctors, to increase the quantity and quality of physical activity (PA) and improve eating habits. Methods: a 5-step protocol was carried out at schools: 1) family and personal background questionnaire for children; 2) body mass index (BMI); 3) bioimpedance corporal composition (BIA); 4) hand grip dynamometry (DIN); and 5) medical physical examination. As a result, each subject received a medical report about his/her diagnosis of body weight and composition and cardiovascular health, and also recommendations to improve eating habits and increase physical activity. Results: in the first two years of PESCA, the weekly time of physical activity has significantly increased among participants (up to 20.12 %; p < 0.001). In addition, the prevalence of overweight/obesity has significantly declined in both girls and children under 6 years of age (35.78 % and 58.92 %; p < 0.05, respectively). Conclusion: the school, pediatrician, and family working together on a transversal intervention has shown effectiveness in reducing the lack of diagnosis and prevalence of overweight and obesity in children.

INTRODUCCIÓN: Introducción: el 40 % de los niños entre los 6 y 9 años en España presentan exceso de peso infantil (EPI). Más de 2/3 padecerán enfermedad cardiovascular en la vida adulta. Aun así, no existe un modelo protocolarizado de acción con el que combatir, de forma eficaz, el problema. El objetivo del programa PESCA es la reducción de la prevalencia del EPI a través de un modelo transversal de actuación que, tomando como centro la red escolar y su profesorado, implique a las familias y la red de atención primaria de salud para actuar mediante la mejora cualitativa y cuantitativa de la actividad física (AF) y los hábitos de alimentación. Métodos: el protocolo incluye 5 pasos que se realizan en el centro escolar: 1) cuestionario de antecedentes personales y familiares de cada alumno; 2) índice de masa corporal (IMC); 3) bioimpedancia de composición corporal (BIA); 4) dinamometría de mano (DIN), y 5) exploración física facultativa. Como resultado, cada sujeto participante recibe un informe facultativo con su diagnostico individualizado de peso corporal y salud cardiovascular, y recomendaciones de mejora en cuanto a AF y hábitos de alimentación. Resultados: en los dos primeros años del programa se ha objetivado un aumento del tiempo semanal dedicado a la AF entre los sujetos participantes (hasta un 20,12 %; p < 0,001) y un descenso significativo en la prevalencia del EPI en las niñas y los menores de 6 años (35,78 % y 58,92 %; p < 0,05, respectivamente). Conclusión: la actuación transversal de colegio, pediatra y familia permite disminuir tanto el déficit diagnóstico de la obesidad y el sobrepeso infantiles como su prevalencia.

Size Does Matter: Litter Size Strongly Determines Adult Metabolism in Rodents.

In this essay, we highlight how litter size in rodents is a strong determinant of neonatal growth and long-term metabolic health. Based on these effects, we strongly advise that scientific articles that utilize rodent models for obesity and metabolic research should include information on the litter sizes in the study to increase the data transparency of such reports.

Specific Dietary Components and Gut Microbiota Composition are Associated with Obesity in Children and Adolescents with Prader-Willi Syndrome.

Prader-Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader-Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader-Willi syndrome.

Plasma Metabolome Alterations Associated with Extrauterine Growth Restriction.

Very preterm infants (VPI, born at or before 32 weeks of gestation) are at risk of adverse health outcomes, from which they might be partially protected with appropriate postnatal nutrition and growth. Metabolic processes or biochemical markers associated to extrauterine growth restriction (EUGR) have not been identified. We applied untargeted metabolomics to plasma samples of VPI with adequate weight for gestational age at birth and with different growth trajectories (29 well-grown, 22 EUGR) at the time of hospital discharge. A multivariate analysis showed significantly higher levels of amino-acids in well-grown patients. Other metabolites were also identified as statistically significant in the comparison between groups. Relevant differences (with corrections for multiple comparison) were found in levels of glycerophospholipids, sphingolipids and other lipids. Levels of many of the biochemical species decreased progressively as the level of growth restriction increased in severity. In conclusion, an untargeted metabolomic approach uncovered previously unknown differences in the levels of a range of plasma metabolites between well grown and EUGR infants at the time of discharge. Our findings open speculation about pathways involved in growth failure in preterm infants and the long-term relevance of this metabolic differences, as well as helping in the definition of potential biomarkers.