Jesús M. Garagorri

Interplay Between Weight Loss and Gut Microbiota Composition in Overweight Adolescents

The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty‐six adolescents (13–15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie‐restricted diet (10–40%) and increased physical activity (15–23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real‐time PCR before and after the intervention. A group of subjects (n = 23) experienced >4.0 kg weight loss and showed significant BMI (P = 0.030) and BMI z‐score (P = 0.035) reductions after the intervention, while the other group (n = 13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P = 0.001) and Lactobacillus group (P = 0.030) counts, and to decreased Clostridium coccoides group (P = 0.028), Bifidobacterium longum (P = 0.031), and Bifidobacterium adolescentis (P = 0.044) counts. In the high weight–loss group, B. fragilis group and Lactobacillus group counts also increased (P = 0.001 and P = 0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P = 0.001 and P = 0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P < 0.001–0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P < 0.001–0.008) in the high weight–loss group than in the low weight–loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individuals microbiota.

Homeostatic model assessment (HOMA) index cut-off values to identify the metabolic syndrome in children

The aim of the study was to establish the best cut-off value for the homeostatic model assessment (HOMA) index in identifying children and adolescents with the metabolic syndrome. The study included 72 non-obese and 68 obese children aged 7 to 16 years. Obesity is defined using the criteria proposed by Coleet al., being included as metabolic syndrome variables waist circumference, systolic blood pressure, diastolic blood pressure and seric values of glucose, uric acid, fasting insulin, leptin, triglycerides and HDL-cholesterol. Children were considered as having the metabolic syndrome when four or more characteristics showed abnormal values. The HOMA index was calculated as the product of the fasting plasma insulin level (μU/mL) and the fasting plasma glucose level (mmol/L), divided by 22.5. HOMA index cut-offs from the 5th to the 95th percentile were used. A receiver operating characteristic (ROC) curve was generated using the different HOMA cut-offs for the screening of the metabolic syndrome. The areas under the ROC curve, 95% confidence intervals, and the point to the ROC curve closest to 1, were calculated. The area under the ROC curve was 0.863 (95% C.I.: 0.797, 0.930). The point closest to 1 corresponds to the 60th percentile of the HOMA index distribution in our sample. HOMA index value at the 60th percentile was 2.28. Cut-off values corresponding to a range of HOMA index from the 50 to the 75 percentile, showed similar distances to 1. HOMA index values for percentiles 50 to 75 ranged from 2.07 to 2.83. In conclusion, HOMA index could be a useful tool to detect children and adolescents with the metabolic syndrome. HOMA cut-off values need to be defined in the paediatric population; however, values near to 3 seem to be adequate.ResumenEl objetivo del estudio era establecer el mejor punto de corte del índice HOMA (Homeostatic Model Assessment) para la identificación de niños y adolescentes con el síndrome metabólico. Se incluyeron 72 niños noobesos y 68 obesos, con edades entre 7 y 16 años. Se definió obesidad según los criterios propuestos por Cole y cols. Las variables utilizadas para describir el síndrome metabólico fueron las siguientes: Perímetro de la cintura, tensión arterial sistólica y diastólica, glucosa, ácido úrico, insulina en ayunas, leptina, triglicéridos y HDL-colesterol. Se consideraba que un niño tenía el síndrome metabólico cuando presentaba cuatro o más de estas características con valores anormales. El índice HOMA se calculó como el producto de las concentraciones de insulina en ayunas (μU/mL) y la glucosa plasmática en ayunas (mmol/L), dividido por 22.5. Se calcularon puntos de corte del índice HOMA correspondientes a los percentiles entre 5 y 95. Se elaboró una curva ROC (Receiver Operating Characteristics) tomando los diferentes puntos de corte del índice HOMA para la identificación del síndrome metabólico. Se calculó el área bajo la curva ROC, los intervalos de confianza al 95% y el punto de la curva ROC más cercano a 1. El área bajo la curva fue 0.863 (IC 95%: 0.797, 0.930). El punto más cercano a 1 correspondía al percentil 60 del índice HOMA en nuestra muestra. El valor del índice HOMA para el percentil 60 era 2.28. Puntos de corte del índice HOMA correspondientes a los percentiles comprendidos entre 50 y 75, mostraban distancias similares a 1. Los valores de índice HOMA correspondientes a estos percentiles oscilaban entre 2.07 y 2.83. En conclusión, el índice HOMA puede ser un buen instrumento para detectar el síndrome metabólico en niños y adolescentes. Es necesario definir mejor el punto de corte a utilizar en la población pediátrica; sin embargo, valores cercanos a 3 parecen ser los más adecuados.

Body composition in adolescents: measurements and metabolic aspects

INTRODUCTION: Adolescence is a decisive period in human life in which important body composition changes occur. Increase of total body mass and its relative distribution are mainly related to gender and pubertal development.OBJECTIVE: This review explores the specific measurements that may be used in this age group to assess excess body fat and to define obesity and overweight.RESULTS: Identification of subjects at risk for adiposity requires simple anthropometric cutoffs for the screening of overweight and obesity. In this context, BMI criterion is the most frequently used but, in spite of its high sensitivity and specificity, an important number of adolescents classified as overweight or obese do not have really high adiposity (32.1% of females and 42% of males). Excess total body fat and intra-abdominal visceral fat are related to metabolic abnormalities that increase the risk of cardiovascular diseases. Waist circumference seems to be the best simple anthropometric predictor for the screening of the metabolic syndrome in children and adolescents.CONCLUSIONS: Early identification of adolescents at risk for adiposity and its related metabolic complications requires reliable, simple and specific measures of excess body fat for this age group.

Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study

In recent years, epigenetic markers emerged as a new tool to understand the influence of lifestyle factors on obesity phenotypes. Adolescence is considered an important epigenetic window over a humans lifetime. The objective of this work was to explore baseline changes in DNA methylation that could be associated with a better weight loss response after a multidisciplinary intervention program in Spanish obese or overweight adolescents. Overweight or obese adolescents (n=107) undergoing 10 wk of a multidisciplinary intervention for weight loss were assigned as high or low responders to the treatment. A methylation microarray was performed to search for baseline epigenetic differences between the 2 groups (12 subjects/group), and MALDI‐TOF mass spectrometry was used to validate (n=107) relevant CpG sites and surrounding regions. After validation, 5 regions located in or near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 genes showed differential methylation levels between high and low responders to the multidisciplinary weight loss intervention. Moreover, a calculated methylation score was significantly associated with changes in weight, BMI‐SDS, and body fat mass loss after the treatment. In summary, we have identified 5 DNA regions that are differentially methylated depending on weight loss response. These methylation changes may help to better understand the weight loss response in obese adolescents.—Moleres, A., Campión, J., Milagro, F. I., Marcos, A., Campoy, C., Garagorri, J. M., Gómez‐Martínez, S., Martínez, J. A., Azcona‐Sanjulián, M. C., Martí, A. Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB J. 27, 2504–2512 (2013). www.fasebj.org

Insulin resistance and impaired glucose tolerance in obese children and adolescents

In developed countries, obesity prevalence has strongly increased in the last decades. This has also been observed in children and adolescents. Until recently, type 2 diabetes mellitus was considered very rare among children and adolescents; however, in the last decades, some cases have been observed mainly in obese adolescents of some minority populations. The aim of our study was to assess the prevalence of type 2 diabetes, impaired glucose tolerance (IGT) and insulin resistance, and the metabolic features, in obese children and adolescents. We have studied 95 obese children and adolescents, 53 males and 42 females, aged 4–16 years. The prevalence of IGT in obese children and adolescents studied was 7.4%; there was not any child with type 2 diabetes. Fasting glucose and insulin serum concentrations did not show significant differences between obese children with or without IGT; however, 120 minutes after an oral glucose tolerance test, glucose and insulin serum concentrations showed statistically significant differences between both groups. Insulin resistance is defined as a HOMA index higher than 4. The prevalence of insulin resistance in obese children studied was 35.8%. Trygliceride serum concentrations were higher and HDL-C serum concentrations were lower in obese children with IGT than in those without IGT, but the differences were not statistically significant. IGT and insulin resistance are frequent in obese children and adolescents; early treatment in obese children and adolescents with IGT constitutes a strategy of reversing progression to β-cell failure and in preventing type 2 diabetes.ResumenLa prevalencia de obesidad en los países desarrollados ha aumentado de manera alarmante en las últimas décadas. Esto se ha observado también en niños y adolescentes. Clásicamente, la diabetes tipo 2 se consideraba muy rara en niños y adolescentes; sin embargo, en las últimas décadas, se han observado algunos casos, especialmente en adolescentes obesos de algunas poblaciones minoritarias. El objetivo de nuestro estudio consiste en valorar la prevalencia de diabetes tipo 2, intolerancia a la glucosa (IG) y resistencia a la insulina, y sus principales manifestaciones, en niños y adolescentes obesos. Se estudiaron 95 niños y adolescentes obesos, 53 varones y 42 mujeres, de 4 a 16 años. La prevalencia de IG en los niños y adolescentes obesos estudiados fue de 7.4%; no se detectó ningún niño con diabetes tipo 2. Las concentraciones séricas en ayunas de glucosa e insulina no mostraron diferencias significativas entre los niños obesos con y sin IG; sin embargo, 120 minutos después de la sobrecarga oral con glucosa, las concentraciones séricas de glucosa e insulina mostraron diferencias significativas entre ambos grupos. La resistencia a la insulina se definió cuando el índice HOMA fue mayor que 4. La prevalencia de resistencia a la insulina en los niños obesos estudiados fue 35,8%. Las concentraciones séricas de triglicéridos fueron mayores y las de HDL-C menores en los niños obesos con IG que en aquellos que no la presentaban, pero las diferencias no fueron estadísticamente significativas. La IG y la resistencia a la insulina son frecuentes en niños y adolescentes obesos; el inicio de un tratamiento precoz en los niños y adolescentes obesos con IG puede evitar el deterioro de la función de las células β y contribuir a prevenir la aparición de diabetes tipo 2 en el futuro.

Reference levels for 17-hydroxyprogesterone, 11-desoxycortisol, cortisol, testosterone, dehydroepiandrosterone sulfate and androstenedione in infants from birth to six months of age.

Reference plasma adrenal steroid levels during early infancy are frequently used to verify hormone measurements when any adrenal abnormality is suspected. We aim to obtain longitudinal reference plasma levels for 17-hydroxyprogesterone (17OHP), 11-desoxycortisol (11DOC), cortisol, dehydroepiandrosterone sulfate (DHEAS), testosterone, and androstenedione in healthy infants from birth to 6 months of age. In 138 term infants, 80 males and 58 females, plasma steroid levels were measured using specific RIA procedures at birth and on the 3rd, 15th, 30th, 60th, 90th, 120th, 150th, and 180th days of life. Smoothed percentiles for each variable were calculated according to the LMS method (LMS program version 1.16, Institute of Child Health, London). Except for cortisol, plasma levels of adrenal steroids decreased progressively from birth to 6 months of age. Plasma concentrations of 17OHP, 11DOC, and cortisol did not show gender differences, but testosterone and androstenedione were significantly higher in boys, and DHEAS levels were higher in girls. Longitudinal reference plasma levels for 17OHP, 11DOC, cortisol, DHEAS, testosterone, and androstenedione have been described in an adequate sample of healthy infants from birth to 6 months of age. These standards, displayed as smoothed percentiles, may be used as reference values in the management of congenital endocrine (adrenal or gonadal) abnormalities that appear in the first weeks of life.

Diversity of metabolic syndrome risk factors in obese children and adolescents

The aim of this study was to investigate the frequency of metabolic syndrome (MS) variables in a group of spanish obese children and adolescents, to asses MS prevalence in this population and to describe it’s relationship with other metabolic risk factors. 103 children were studied: 54 male and 49 female, mean age 10.08±2.3 with exogenous obesity. Obesity was defined when BMI was higher than the age and sex specific equivalent to 30 kg/m2 in adults. MS variables considered were waist circumference, blood pressure, fasting blood triglycerides, fasting glucose/insulin and HDL-cholesterol. The children were considered as having the MS when three or more characteristics showed abnormal values according to Cook and De Ferranti definitions. HOMA index, ApoB and ApoA1 were studied too. The most frequent features of the metabolic syndrome were excess waist circumference and hypertension. The MS markers with the lowest frequency were dyslipidemia and fasting hyperglicemia. MS prevalence was 29,9% (Cook et al. criteria) and 50% (De Ferranti et al. criteria). Fasting insulin and HOMA index values increased significantly (p < 0.05) when three or more abnormalities of the MS variables were present. Apo B increased significantly only in females (p < 0.05) and Apo A1 decreased significantly (p < 0.05) in both sexes when MS was present. Adequate metabolic syndrome risk factors criteria, mainly cut-off values, need to be defined in the European paediatric population.ResumenEl objetivo de este trabajo es el estudio de la frecuencia de presentación de los diferentes componentes del Síndrome Metabolico (SM) en un grupo de niños y adolescentes obesos españoles, determinar la prevalencia del SM en esa población e investigar el comportamiento de otros factores de riesgo metabólico. Se han estudiado 103 pacientes (54 varones y 49 mujeres), diagnosticados de obesidad exógena y con edad media de 10,08 ±2,3 años. Como criterio de obesidad se han tenido en cuenta los criterios internacionales de Coleet al., cuando el IMC es mayor o igual al equivalente a 30 Kg/m2 para edad y sexo. Como variables del SM se han considerado: perímetro de cintura, tensión arterial, triglicéridos, glucemia/insulinemia y HDL-colesterol, todos ellos tras ayuno de 12 horas. Se hizo el diagnóstico de SM cuando tres o más variables presentaban valores anormales, siguiendo los criterios propuestos por Cook y de Ferranti. Se han estudiado también el índice HOMA y las cifras de ApoB y ApoA1. Los componentes del SM más frecuentes fueron el incremento del perímetro de cintura y la hipertensión. Los menos frecuentes fueron la dislipidemia y la hiperglucemia. El diagnóstico de SM se hizo en el 29,9% (criterio de Cooket al.) y 50% (criterio de De Ferrantiet al.) de los pacientes. La insulinemia basal y el HOMA se incrementaron significativamente cuando existían más de tres anomalías del SM (p < 0,05). La Apo B aumentó significativamente en el sexo femenino (p<0,05) y la Apo A1 disminuyó (p < 0,05) en ambos sexos en los pacientes con diagnóstico de SM. Son necesarios más estudios para precisar los puntos de corte más adecuados de los factores de riesgo que componen el SM en la población infantil europea

Psyllium fibre and the metabolic control of obese children and adolescents

In children and adolescents from developed countries, obesity prevalence has strongly increased in the last decades and insulin resistance and impaired glucose tolerance are frequently observed. Some dietary components such as low glycemic index foods and dietary fibre could be used in order to improve glucose homeostasis in these children. Psyllium or ispaghula husk (the husk of the seeds ofPlantago ovata) is a mixture of neutral and acid polysaccharides containing galacturonic acid with a ratio of soluble / insoluble fibre of 70 / 30. Some foods could potentially be enriched with psyllium, like breads, breakfast cereals, pasta and snack foods. The aim of this review was to assess the usefulness of psyllium in the management of obese children and adolescents with abnormalities of carbohydrate and lipid metabolism. After psyllium supplementation, the percentage change in postprandial glucose in type 2 diabetes patients, ranged from −12.2 to −20.2%. In hypercholesterolemic children, the effect of psyllium in LDL-cholesterol serum concentrations ranged from 2.78 to −22.8%; the effect in HDL-cholesterol from −4.16 to 3.05%; and the effect on triglycerides from 8.49 to −19.54%. The reviewed evidence seems to show that psyllium improves glucose homeostasis and the lipid and lipoprotein profile; however, more well controlled trials and further studies are needed to clarify it’s effects and the mechanisms involved.ResumenLa resistencia a la insulina y la intolerancia a la glucosa se observan con frecuencia en niños y adolescentes obesos. La prevalencia de la obesidad ha aumentado de manera considerable en las últimas décadas en los niños y adolescentes de los países desarrollados. Algunos componentes de la dieta, como los alimentos con un índice glucémico bajo o la fibra dietética se podrían usar para mejorar la homeostasis de la glucosa en estos niños. El psyllium es la piel de las semillas dePlantago ovata, que constituye una mezcla de polisacáridos ácidos y neutros con un resto de ácido galacturónico y una relación fibra soluble / insoluble de 70 / 30. Algunos alimentos pueden ser enriquecidos potencialmente con psyllium, como el pan, los cereales del desayuno, la pasta y lossnacks. En esta revisión, se valora la utilidad del psyllium para el tratamiento de los niños y adolescentes con anomalías del metabolismo de los hidratos de carbono y los lípidos. En pacientes con diabetes tipo 2, tras la suplementación con psyllium, el porcentaje de cambio en la glucosa postprandial oscilaba entre −12.2 y −20.2%. En niños con hipercolesterolemia, el efecto del psyllium en las concentraciones séricas de LDL-colesterol oscilaba entre 2.78 y −22.8%; el efecto en HDL-colesterol entre −4.16 y 3.05%; y el efecto en los triglicéridos entre 8.49 y −19.54%. Los estudios revisados parecen mostrar que el psyllium mejora la homeostasis de la glucosa y el metabolismo de los lípidos y lipoproteínas; sin embargo, se necesitan más estudios controlados e investigación básica con el fin de aclarar sus efectos y los mecanismos básicos involucrados en ellos.

Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study

BackgroundThe prevalence of overweight and obesity (OW/OB) among adolescents worldwide has increased since the 60 s. Spain has reached one of the highest OW/OB prevalence rates among adolescents from European countries. The aim of this methodological paper is to describe the design and evaluation in the EVASYON study (Development, implementation and evaluation of the efficacy of a therapeutic programme for adolescents with OW/OB: integral education on nutrition and physical activity).Methods/DesignThe EVASYON was planned by a multidisciplinary team to treat OW/OB in Spanish adolescents. The EVASYON is a multi-centre study conducted in 5 hospitals in 5 Spanish cities (Granada, Madrid, Pamplona, Santander and Zaragoza) and two hundred and four OW/OB Spanish adolescents were recruited for this intervention. The treatment was implemented for approximately one-year follow-up. The adolescents were treated in groups of a maximum of 10 subjects; each group had 20 visits during the treatment period in two phases: intensive during the first 2 months (1st to 9th visits), and extensive during the last 11 months (10th to 20th visits). In order to assess the efficacy of the treatment, 8 dimensions were measured: diet; physical activity and fitness; eating behaviour; body composition; haematological profile; metabolic profile; minerals and vitamins; immuno-inflammatory markers. Moreover, genetic polymorphisms were also determined.DiscussionThe treatment programme developed in the EVASYON study was designed as a national pilot study to be implemented as an effective treatment for adolescents with OW/OB into the Spanish Health Care Service.

Changes in cardiometabolic risk factors, appetite-controlling hormones and cytokines after a treatment program in overweight adolescents: preliminary findings from the EVASYON study.

Romeo J, Martinez‐Gomez D, Diaz LE, Gómez‐Martinez S, Marti A, Martin‐Matillas M, Puertollano MA, Veiga OL, Martinez JA, Wärnberg J, Zapatera B, Garagorri JM, Morandé G, Campoy C, Moreno LA, Marcos A; EVASYON Study Group. Changes in cardiometabolic risk factors, appetite‐controlling hormones and cytokines after a treatment program in overweight adolescents: preliminary findings from the EVASYON study