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Importance: Excess abdominal fat is a major determinant in the development of insulin resistance and other metabolic disorders. Increased visceral adipose tissue (VAT) seems to precede the development of insulin resistance and is therefore a prime target of childhood lifestyle interventions aimed at preventing diabetes., Objectives: To examine the effect of added exercise to a family-based lifestyle intervention program designed to reduce VAT plus subcutaneous (ASAT), intermuscular (IMAAT), and pancreatic (PAT) adipose tissue in children with overweight or obesity and to explore the effect of changes in VAT on insulin resistance., Design, Setting, and Participants: This 2-group, parallel-design clinical trial was conducted in Vitoria-Gasteiz, Spain. A total of 116 children with overweight or obesity participated and were assigned to a 22-week family-based lifestyle program (control group [n = 57]) or the same program plus an exercise intervention (exercise group [n = 59]). Data were collected between September 1, 2014, and June 30, 2017, and imaging processing for fat depot assessments and data analysis were performed between May 1, 2019, and February 12, 2021., Interventions: The compared interventions consisted of a family-based lifestyle and psychoeducation program (two 90-minute sessions per month) and the same program plus supervised exercise (three 90-minute sessions per week)., Main Outcomes and Measures: The primary outcome of this study was the change in VAT between baseline and 22 weeks as estimated by magnetic resonance imaging. The secondary outcomes were changes in ASAT, IMAAT, and PAT. The effect of changes in VAT area on insulin resistance was also recorded., Results: The 116 participants included in the analysis (62 girls [53.4%]) had a mean (SD) age of 10.6 (1.1) years, and 67 (57.8%) presented with obesity. Significantly greater reductions were recorded for the exercise group in terms of reduction in VAT (-18.1% vs -8.5% for the control group; P = .004), ASAT (-9.9% vs -3.0%; P = .001), and IMAAT (-6.0% vs -2.6%; P = .02) fat fractions compared with the control group. Changes in VAT explained 87.6% of the improvement seen in insulin resistance (β = -0.102 [95% CI, -0.230 to -0.002])., Conclusions and Relevance: These findings suggest that the addition of exercise to a lifestyle intervention program substantially enhanced the positive effects on abdominal fat depots in children with overweight or obesity. In addition, the reduction in VAT seemed to largely mediate the improvement of insulin sensitivity. These results highlight the importance of including exercise as part of lifestyle therapies aimed at treating childhood obesity and preventing the development of type 2 diabetes., Trial Registration: ClinicalTrials.gov Identifier: NCT02258126.

Background: The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging., Objective: To develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis., Methods: A total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression., Results: Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p < 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical- and/or SNPs-based predictive models were developed, showing strong discriminatory capacity (AUC-ROC: 0.708-0.888) but limited diagnostic performance (sensitivity 67%-82% and specificity 63%-69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%., Conclusions: The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Hepatic steatosis (HS) is currently the most prevalent hepatic disease in paediatric population and a major risk factor for type 2 diabetes and cardiovascular diseases. The proper identification of children with HS is therefore of great public health interest., Objective: To develop a new prediction score using anthropometric, sociodemographic and lifestyle factors to identify children with HS (the HEPAKID index). Previously published biochemical paediatric screening tools were validated in the same cohort., Methods: A total of 115 pre-adolescent children aged 8 to 12 years with overweight/obesity, recruited at hospital paediatric units were enrolled in this cross-sectional study. HS (≥5.5% hepatic fat) was assessed by magnetic resonance imaging (MRI). Anthropometric, sociodemographic and lifestyle variables were collected by validated tests/questionnaires., Results: Forty-one children had MRI-diagnosed HS (35.6%, 49% girls). These children had (P < .01) a higher waist-height ratio, a lower cardiorespiratory fitness, a younger gestational age, and consumed more sugar-sweetened beverages than their HS-free peers. Children with HS were more likely to belong to an ethnic minority (P < .01) and to spend longer viewing screens than recommended (P < .05). The addition of these variables to the multivariate logistic regression model afforded a HEPAKID index with high discriminatory capacity (area under the receiver-operating characteristic curve: 0.808, 95% CI 0.715-0.901), and score of ≥25.0 was associated with high sensitivity (82%, 95% CI 68%-96%). Biochemical biomarker-based paediatric tools for identifying HS showed only moderate discriminatory capacity and low sensitivity (5%-41%) in this cohort., Conclusions: The HEPAKID index is the first simple, non-invasive, sensitive, inexpensive and easy-to-perform screening that can identify children with overweight or obesity who have HS., (© 2021 World Obesity Federation.)

Background: Non-alcoholic fatty liver disease is the most common liver disease in childhood and is related to insulin resistance and cardiometabolic risk factors. Evidence supporting the association of fitness and physical activity with hepatic fat, liver enzymes, or triglyceride-to-high-density lipoprotein ratio is scarce in children., Objective: To analyze the associations of physical fitness and physical activity (PA) with percentage hepatic fat, liver enzymes, insulin resistance, and cardiometabolic risk in children with overweight/obesity., Subjects: A total of 115 children (10.6 ± 1.1 years; 54% girls) with overweight/obesity of the EFIGRO study (ClinicalTrials.gov: NCT02258126) were included in the analyses., Methods: Cardiorespiratory fitness (CRF), musculoskeletal fitness and speed-agility were measured by the Alpha-fitness tests, and PA by wGT3X-BT accelerometers. Percentage hepatic fat was assessed by magnetic resonance imaging. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), insulin, glucose, triglycerides (TG), and high-density lipoprotein (HDL) levels were obtained from fasting blood samples. The homeostasis model assessment insulin resistance (HOMA-IR) and AST/ALT and TG/HDL ratios were calculated., Results: Higher CRF was associated with lower percentage hepatic fat (β = -0.266, P = .01) and GGT (β = -0.315, P < .01), and higher AST/ALT ratio (β = 0.306, P < .01). CRF-fit children have lower GGT levels (15 ± 1 vs 17 ± 1 U/L, CRF-fit vs CRF-unfit children, P = .02), HOMA-IR (2.2 ± 0.1 vs 2.9 ± 0.1, P < .01) and TG/HDL ratio (1.4 ± 0.1 vs 1.9 ± 0.1, P = .01) and higher AST/ALT ratio (1.3 ± 0.0 vs 1.2 ± 0.0, P = .03), than CRF-unfit children., Conclusions: These findings emphasize the importance of considering the improvement of CRF as a target of programs for preventing hepatic steatosis, type 2 diabetes and cardiovascular diseases in children with overweight., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Healthy lifestyle education programs are recommended for obesity prevention and treatment. However, there is no previous information on the effects of these programs on the reduction of hepatic fat percentage. The aims were (i) to examine the effectiveness of a 22-week family-based lifestyle education program on dietary habits, and (ii) to explore the associations of changes in dietary intake with percent hepatic fat reduction and adiposity in children with overweight/obesity. A total of 81 children with overweight/obesity (aged 10.6 ± 1.1 years, 53.1% girls) and their parents attended a 22-week family based healthy lifestyle and psychoeducational program accompanied with (intensive group) or without (control) an exercise program. Hepatic fat (magnetic resonance imaging), adiposity (dual energy X-ray absorptiometry) and dietary habits (two non-consecutive 24 h-recalls) were assessed before and after the intervention. Energy ( p < 0.01) fat ( p < 0.01) and added sugar ( p < 0.03) intake were significantly reduced in both groups at the end of the program, while, in addition, carbohydrates intake ( p < 0.04) was reduced exclusively in the control group, and simple sugar ( p < 0.05) and cholesterol ( p < 0.03) intake was reduced in the exercise group. Fruit ( p < 0.03) and low-fat/skimmed dairy consumption ( p < 0.02), the adherence to the Mediterranean Diet Quality Index for children and teenagers (KIDMED, p < 0.01) and breakfast quality index ( p < 0.03) were significantly higher in both control and intervention groups after the intervention. Moreover, participants in the exercise group increased the adherence to the Dietary Approaches to Stop Hypertension (DASH) diet ( p < 0.001), whereas the ratio of evening-morning energy intake was significantly lower exclusively in the control group after the program ( p < 0.02). Changes in energy intake were significantly associated with changes in fat mass index (FMI) in the exercise group, whereas changes in sugar-sweetened beverages (SSB) consumption was associated with percent hepatic fat reduction ( p < 0.05) in the control group. A 22-week family-based healthy lifestyle program seems to be effective on improving diet quality and health in children with overweight/obesity and these should focus on SSB avoidance and physical activity.

Background/objective: Exercise and lifestyle interventions have been shown to reduce hepatic fat (HF) and adiposity in youth. However, the interindividual response in HF after a lifestyle intervention with or without exercise in children is unknown. The aim of the present study was to compare interindividual variability for HF, adiposity, gamma-glutamyl transferase (GGT), and the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) in children with overweight/obesity participating in a 22-week lifestyle intervention with (intensive intervention) or without exercise (control intervention)., Methods: Data from 102 children (9-12 years, 55% girls) with overweight/obesity participating in the EFIGRO randomized controlled trial were analyzed. Percentage HF (magnetic resonance imaging), weight, body and fat mass index (BMI and FMI), GGT, AST/ALT, cardiorespiratory fitness (CRF, 20 meters shuttle run test) were assessed before and after the intervention by the same trained researchers. The control intervention consisted in 11 sessions of a family-based lifestyle and psycho-educational program. The intensive intervention included the control intervention plus supervised exercise (3 sessions/week)., Results: The prevalence of responders for HF (54% vs. 34%), weight (27% vs. 11%), BMI (71% vs. 47%), FMI (90% vs. 60%), and GGT (69% vs. 39%) was higher in the intensive than in the control group (Ps < 0.05). Responders for weight (16 ± 3 vs. 6 ± 2 laps) and BMI (11 ± 2 vs. 3 ± 4 laps) improved more CRF levels than non-responders (Ps < 0.05)., Conclusions: The addition of exercise to a lifestyle intervention may increase the responder rates for HF, adiposity, and GGT in children with overweight/obesity. Improvements in CRF may explain differences between weight and BMI responders and non-responders., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02258126., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Pediatric hepatic steatosis is highly prevalent and closely related to type 2 diabetes. This study aimed to determine whether the addition of supervised exercise to a family-based lifestyle and psycho-educational intervention results in greater reduction of percentage of hepatic fat (HF), adiposity, and cardiometabolic risk factors in children with overweight/obesity., Research Design and Methods: The study subjects of this nonrandomized, two-arm, parallel design clinical trial were 116 overweight/obese children (10.6 ± 1.1 years of age, 53.4% girls) living in Vitoria-Gasteiz (Spain). For 22 weeks, they followed either a lifestyle and psycho-education program (control intervention [CInt], N = 57), consisting of two family-based education sessions/month, or the same plus supervised exercise (intensive intervention [II], N = 59) focused mainly on high-intensity aerobic workouts (3 sessions/week, 90 min/session). The primary outcome was the change in percentage of HF (as measured by MRI) between baseline and the end of the intervention period. Secondary outcomes included changes in BMI, fat mass index (FMI), abdominal fat (measured by DEXA), blood pressure, triglycerides, HDL, LDL, γ-glutamyl transferase, glucose, and insulin concentrations., Results: A total of 102 children completed the trial ( N = 53 and N = 49 in the CInt and II groups, respectively). Percentage of HF decreased only in the II group (-1.20 ± 0.31% vs. 0.04 ± 0.30%, II and CInt groups, respectively), regardless of baseline value and any change in adiposity ( P < 0.01). BMI, FMI, abdominal fat ( P ≤ 0.001), and insulin ( P < 0.05) were reduced in both groups., Conclusions: Multicomponent intervention programs that include exercise training may help to reduce adiposity, insulin resistance, and hepatic steatosis in overweight/obese children., (© 2019 by the American Diabetes Association.)

Paediatric non-alcoholic fatty liver disease has increased in parallel with childhood obesity. Dietary habits, particularly products rich in sugars, may influence both hepatic fat and insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR)). The aim of the study was to examine the association of the consumption of foods and food components, dairy desserts and substitutes (DDS), sugar-sweetened beverages (SSB), as well as total and added sugars, with hepatic fat and HOMA-IR. Dietary intake (two non-consecutive 24 h-recalls), hepatic fat (MRI) and HOMA-IR were assessed in 110 overweight/obese children (10·6 (sd 1·1) years old). Linear regression analyses were used to examine the association of dietary intake with hepatic fat and HOMA-IR adjusted for potential confounders (sex, age, energy intake, maternal educational level, total and abdominal adiposity and sugar intake). The results showed that there was a negative association between cereal intake and hepatic fat (β=-0·197, P&lt;0·05). In contrast, both SSB consumption (β=0·217; P=0·028) and sugar in SSB (β=0·210, P=0·035), but not DDS or sugar in DDS or other dietary components, were positively associated with hepatic fat regardless of potential confounders including total sugar intake. In conclusion, cereal intake might decrease hepatic fat, whereas SSB consumption and its sugar content may increase the likelihood of having hepatic steatosis. Although these observations need to be confirmed using experimental evidence, these results suggest that healthy lifestyle intervention programs are needed to improve dietary habits as well as to increase the awareness of the detrimental effects of SSB consumption early in life.

Purpose: Early recognition of risk factors associated with overweight/obesity is an important step towards preventing long-term health consequences. The aim of the current study was to examine the associations of the adherence to the Mediterranean dietary pattern (MDP) and cardiorespiratory fitness (CRF) with adiposity in preschool children from the north of Spain., Methods: The adherence to the MDP (KIDMED), CRF (20-m shuttle run test), total (BMI) and central (waist circumference) adiposity and socio-demographic factors were assessed in 619 children (48.6% girls) who were on average 4.7 years old., Results: Higher MDP index (P < 0.05) and CRF levels (P < 0.01) were significantly related to lower waist circumference. CRF was inversely associated with BMI (P ≤ 0.001), yet no significant association was observed between MDP and BMI. Children not having high CRF levels and high MDP (i.e., non-upper sex-specific tertile of CRF or MDP, respectively) had the highest waist circumference., Conclusions: Our findings support that higher adherence to the MDP and higher CRF are associated with lower waist circumference in preschool children, pointing them as relevant modifiable factors to be targeted by educational strategies aiming to prevent central obesity and later obesity-related comorbidities.

There is a general belief that having breakfast is an important healthy lifestyle factor; however, there is scarce evidence on the influence of breakfast quality and energy density on cardiometabolic risk in children, as well as on the role of physical activity in this association. The aims of this paper were (i) to examine the associations of breakfast quality and energy density from both solids and beverages with cardiometabolic risk factors, and (ii) to explore whether physical activity levels may attenuate these relationships in children with overweight/obesity from two projects carried out in the north and south of Spain. Breakfast consumption, breakfast quality index (BQI) score, BEDs/BEDb (24 h-recalls and the KIDMED questionnaire), and physical activity (PA; accelerometry) were assessed, in 203 children aged 8⁻12 years who were overweight or obese. We measured body composition (Dual X-ray Absorptiometry), uric acid, blood pressure, lipid profile, gamma-glutamyl-transferase (GGT), glucose, and insulin, and calculated the HOMA and metabolic syndrome z -score. The BQI score was inversely associated with serum uric acid independently of a set of relevant confounders (β = -0.172, p = 0.028), but the relationship was attenuated after further controlling for total PA ( p < 0.07). BEDs was positively associated with total and HDL cholesterol, and systolic blood pressure regardless of confounders (all p < 0.05), while BEDb was positively associated with HOMA in either active/inactive children (all p < 0.03). In conclusion, higher breakfast quality and lower breakfast energy density should be promoted in overweight/obesity children to improve their cardiometabolic health.

The main purposes of this study were to elucidate the effects of supervised-exercise training (ET) interventions on hepatic fat content and on non-alcoholic fatty liver disease (NAFLD) prevalence in children and adolescents and to provide information about the optimal ET prescription (type, intensity, volume, and frequency) needed to reduce hepatic fat content in youths. Supervised-ET interventions performed in children and adolescents (6-19 years) that provided results of exercise effects on hepatic fat content or NAFLD prevalence were included. Supervised-exercise significantly reduced hepatic fat content compared to the control groups. Lifestyle interventions that included supervised-ET significantly reduced the prevalence of NAFLD. This systematic review and meta-analysis shows that supervised-ET could be an effective strategy in the management and prevention of NAFLD in children and adolescents. Both aerobic and resistance ET, at vigorous or moderate-to-vigorous intensities, with a volume ≥60 min/session and a frequency ≥3 sessions/week, aiming to improve cardiorespiratory fitness and muscular strength, had benefits on hepatic fat content reduction in youth. These data concur with the international recommendations of physical activity for health promotion in youth and may be useful when designing ET programs to improve and prevent hepatic steatosis in the pediatric population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The global pandemic of obesity has led to an increased risk for prediabetes and type-2 diabetes (T2D). The aims of the current project are: (1) to evaluate the effect of a 22-week family based intervention program, including supervised exercise, on insulin resistance syndrome (IRS) risk in children with a high risk of developing T2D and (2) to identify the profile of microRNA in circulating exosomes and in peripheral blood mononuclear cells in children with a high risk of developing T2D and its response to a multidisciplinary intervention program including exercise., Methods: A total of 84 children, aged 8-12 years, with a high risk of T2D will be included and randomly assigned to control (N = 42) or intervention (N = 42) groups. The control group will receive a family based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week, 90 min per session including warm-up, moderate to vigorous aerobic activities, and strength exercises). The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting insulin, glucose and hemoglobin A1c; body composition (dual-energy X-ray absorptiometry); ectopic fat (magnetic resonance imaging); microRNA expression in circulating exosomes and in peripheral blood mononuclear cells (MiSeq; Illumina); cardiorespiratory fitness (cardiopulmonary exercise testing); dietary habits and physical activity (accelerometry)., Discussion: Prevention and identification of children with a high risk of developing T2D could help to improve their cardiovascular health and to reduce the comorbidities associated with obesity., Trial Registration: ClinicalTrials.gov, ID: NCT03027726 . Registered on 16 January 2017.