Cristina Azcona

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.

Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents.

AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene to obesity risk in a Spanish children and adolescent population.METHODS: We designed a sex- and age-matched case–control study. Participants were 185 obese and 185 control children (aged 5–18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPARγ2 mutation and BstNI for ADRβ3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls.RESULTS: Carriers of the polymorphism Pro12Ala of the PPARγ2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09–4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17–5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPARγ2 and ADRβ3) was 5.30 (95% CI=1.08–25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43–146.8).CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene for obesity risk was found in a case–control study including children and adolescents.

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.

Reduced Bone Mineralization in Adolescent Survivors of Malignant Bone Tumors: Comparison of Quantitative Ultrasound and Dual-Energy X-Ray Absorptiometry

Purpose To assess bone mineralization in adolescents with bone tumors at remission using quantitative digital ultrasound (QUS) and dual-energy x-ray absorptiometry (DEXA), and to compare the bone mineralization values obtained by both methods. Methods Patients studied were 36 adolescents (21 boys, 15 girls) who had completed treatment of a bone tumor at the University Hospital of the University of Navarra (Pamplona, Spain). QUS was performed at the distal metaphysis of the proximal phalanxes of the last four fingers of the nondominant hand. A DBM Sonic 1200 Ultrasound densitometer was used. DEXA measurements were made at the lumbar spine (vertebrae L1–L4) using the Hologic QDR 4500 W device. Calcium and vitamin D daily intake and grade of physical activity were recorded. Results Mean age at bone mineralization determination was 19.11 years. Disease-free survival was 4.97 years. Decreased bone mineralization was observed by both methods. Bone mineralization absolute values measured by QUS and DEXA were significantly correlated. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of QUS for predicting osteopenia were 36.4%, 80.0%, 66.7%, 44.4%, and 74.1%, respectively. Daily vitamin D intake was below the recommended dietary allowances. Conclusions Adolescents in remission from bone tumors have low bone mineralization determined by DEXA or QUS.

Effect of Long-Term Growth Hormone Treatment on Final Height of Children with Russell-Silver Syndrome

Background: The aim of this study was to determine the beneficial effects of long-term growth hormone (GH) treatment on final height (FH) in 26 children with Russell-Silver syndrome (RSS). Methods: Twenty-six patients (16 males) were diagnosed with RSS at a median age of 2.9 years according to clinical criteria. All patients were prepubertal at the commencement of treatment. They received treatment with biosynthetic human GH for 9.8 years (median) and all attained FH. Results: The median height at the commencement of treatment was –2.7 SDS and increased to –1.3 SDS (p = 0.001). However, FH did not reach target height (–0.90 SDS, p = 0.003). Predictors of FH outcome were: the height at the start of treatment (r2 = 0.419, p < 0.001) (inversely related) and the height gain at onset of puberty (r2 = 0.257, p < 0.001) (positively related). The overall prediction model accounted for 67.6% of height gain. Sitting height improved gradually during GH treatment (–3.3 to –1.0 SDS, p = 0.012), as did weight (–3.3 to –1.3 SDS, p < 0.001) and BMI (–1.5 to –0.2 SDS, p < 0.001). Conclusions: A significant improvement of growth in RSS children has been shown after 10 years of GH treatment with a FH of –1.3 SDS. The shorter the patient at the start of treatment is, the greater the increment in FH. A significant response is also shown at the onset of puberty. GH treatment may also have a beneficial effect on the spinal length of RSS children.

Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewings sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)2 vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewings sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewings sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality of life.

Il6 gene promoter polymorphism (-174G/C) influences the association between fat mass and cardiovascular risk factors.

During the last decades, the prevalence of obesity has increased rapidly among young people. A polymorphism in the promoter region of the IL6 gene (-174G/C), has been previously reported to be involved in obesity and metabolic syndrome development. Therefore, the aim of the study was to examine whether the IL6-174G/C polymorphism influence the association of body fat with low-grade inflammatory markers and blood lipids and lipoproteins in Spanish adolescents. 504 Spanish adolescents participating in the AVENA study were genotyped for the-174G/C polymorphism of the IL6 gene. Anthropometric and body composition measurements were taken and blood samples were collected for plasma molecules determinations. No differences between genotypes were observed in anthropometric values, body composition measurements and plasma markers concentration. Physical activity level differ between genotypes with subjects carrying the C allele of the polymorphism being significantly (p<0.05) more active than GG subjects. The association between body fat mass and plasma glucose was influenced by the -174G/C polymorphism of the IL6 gene. Subjects carrying the C allele of the mutation seem to have higher values of lipoprotein (a) and C-reactive protein as their percentage of body fat mass increase. Our results suggest that this promoter polymorphism influences the association between adiposity and some plasma markers.

Serum Amyloid A Concentration is Increased in Obese Children and Adolescents

OBJECTIVE To compare the circulating concentrations of the acute-phase protein serum amyloid A (SAA) in lean, overweight, and obese children and adolescents and analyze the influence of body fat. STUDY DESIGN A total of 63 children and adolescents (65% girls) with an average age of 12.1 +/- 2.7 years (range, 6 to 18 years) were included in the study. Each child was classified on the basis of age- and sex-specific body mass index (BMI) percentile as normal weight (BMI <85th percentile; n = 17), overweight (BMI >/=85th and <95th percentiles; n = 26), or obese (BMI >/=95th percentile; n = 20). Body fat was estimated by air-displacement plethysmography. RESULTS Both overweight and obese children exhibited significantly increased circulating SAA concentrations (log SAA: lean, 0.66 +/- 0.20; overweight, 0.83 +/- 0.29; obese, 0.96 +/- 0.21; P = .002) compared with the lean children. Significant correlations were found between log SAA and body fat (r = 0.48; P < .0001). In multiple linear regression analysis, log C-reactive protein (CRP) (P = .014) and body fat (P = .031) emerged as significant predictors of log SAA. CONCLUSIONS Plasma SAA concentrations are elevated in overweight and obese children, being strongly related to adiposity and log CRP. This finding suggests that increased body fat may contribute to the development of a low-grade chronic proinflammatory state at an early age, possibly contributing to the obesity-associated cardiovascular disease risk.

A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population

Objective  The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation.

Fat mass by air-displacement plethysmography and impedance in obese/non-obese children and adolescents

OBJECTIVE To determine the level of agreement between measurements of body composition by air-displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) in obese/non-obese children and adolescents. METHODS Fat mass (FM) and fat free mass (FFM) were measured by ADP using the BOD-POD system and foot-to-foot BIA in 187 children and adolescents (75 males and 112 females, aged 5 to 22 years). Obesity was defined as a percentage FM (determined by BOD-POD), as a percentage (%) higher than 25%-35%. Sixty-four subjects were obese and 123 non-obese. RESULTS Lins Concordance Coefficient (Rc) between estimates of FM (%) and FFM (kg) was 0.79 (95% CI: 0.73; 0.83) by BIA and 0.96 (95% CI: 0.95; 0.97) by ADP. For the group of patients as a whole, the mean difference (p < 0.001) between methods (the BIA measurement minus the ADP measurement) was -3.39 (95% CI: -4.13; -2.65) for FM (%) and 1.54 (95% CI: 1.10; 1.98) for FFM (kg) (p < 0.001). The limits of agreement were -13.70; 6.90 for FM (%) and 1.40; 7.60 for FFM (kg). In the obese group, the mean difference between methods was -5.01 (95% CI: -6.21; -3.81) for FM (%) and 2.58 (95% CI: 3.45; 1.71) for FFM (kg) (p < 0.001). In the non-obese group, these mean differences were 2.49 (95% CI: -3.41; -1.57) and 0.96 (95% CI: 1.43; 0.50), respectively (p < 0.001). CONCLUSIONS Compared with ADP, foot-to-foot BIA overestimates FFM and underestimates FM in obese and non-obese children of either sex. ADP and BIA estimates of FFM and FM are highly correlated for both obese/non-obese children. However, the large limits of agreement suggest that these methods should not be used interchangeably.