Medrano Echeverría, María

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Medrano Echeverría

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María

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Now showing 1 - 10 of 35
  • PublicationOpen Access
    Effects of exercise in addition to a family-based lifestyle intervention program on hepatic fat in children with overweight
    (American Diabetes Association, 2020) Labayen Goñi, Idoia; Medrano Echeverría, María; Arenaza Etxeberría, Lide; Maiz, Edurne; Osés Recalde, Maddi; Martínez Vizcaíno, Vicente; Ruiz, Jonatan R.; Ortega, Francisco B.; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
    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, gamma-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.
  • PublicationEmbargo
    Association between body shape index and arterial stiffness: results of the EVasCu study and a meta-analysis
    (Springer Nature, 2024-10-28) Saz-Lara, Alicia; Cavero-Redondo, Iván; Moreno-Herráiz, Nerea; Rescalvo-Fernández, Elena; Berlanga-Macías, Carlos; Medrano Echeverría, María; Fuentes Chacón, Rosa María; Pascual-Morena, Carlos; Ciencias de la Salud; Osasun Zientziak
    Objective: The aim of this study was to analyse the association between body shape index (ABSI) and arterial stiffness in healthy subjects using data from the EVasCu study. In addition, a meta-analysis was performed to compare the association between ABSI and central, peripheral and systemic arterial stiffness in the general population. Methods: The EVasCu study included 390 healthy subjects. ABSI was calculated from waist circumference, body mass index and height, and arterial stiffness was assessed with aortic pulse wave velocity (a-PWv) and cardio-ankle vascular index (CAVI). A meta-analysis of previous studies, including data from the EVasCu study, was performed to obtain pooled estimates of correlation coefficients (r) and their respective 95% confidence intervals (95% CIs) for the association between ABSI and central, peripheral and systemic arterial stiffness. In addition, pooled OR estimates and their 95% CIs were calculated. Results: In the EVasCu study, the correlation coefficient estimate was 0.458 (p < 0.01) for the association of a-PWv and ABSI and 0.408 (p < 0.01) for the association of CAVI and ABSI. In the meta-analysis, the pooled correlation coefficient estimate was 0.22 (95% CIs: 0.16, 0.28) for central arterial stiffness and ABSI, 0.21 (95% CIs: 0.14, 0.28) for peripheral arterial stiffness and ABSI, and 0.28 (95% CI: 0.21, 0.3) for systemic arterial stiffness and ABSI. When pooled ORs were calculated, the pooled OR estimate was 2.12 (95% CIs: 1.68, 2.56) for central arterial stiffness and ABSI, 2.21 (95% CIs: 1.81, 2.60) for peripheral arterial stiffness and ABSI, and 2.99 (95% CIs: 2.14, 3.85) for systemic arterial stiffness and ABSI. Conclusion: Based on both the results obtained in the EVasCu study and the meta-analysis, there is a positive association between ABSI and arterial stiffness, both in healthy subjects and in participants with comorbidities. For each unit of cm/kg/m²/m increase in ABSI, the risk of arterial stiffness increased by 112% for central arterial stiffness, 121% for peripheral arterial stiffness, and 199% for systemic arterial stiffness. However, further research is needed in this field of knowledge.
  • PublicationOpen Access
    Effects of time-restricted eating and resistance training on skeletal muscle tissue quantity, quality and function in postmenopausal women with overweight or obesity: a study protocol
    (Elsevier, 2024-12-30) Alfaro-Magallanes, Víctor Manuel; Medrano Echeverría, María; Echarte Medina, Jon; Osés Recalde, Maddi; Izquierdo Rodríguez, Claudia; Concepción Álvarez, Mara de la Caridad; Galbete Jiménez, Arkaitz; Idoate, Fernando; Zugasti Murillo, Ana; Petrina Jáuregui, María Estrella; Goñi Gironés, María Elena; Ribelles, María Jesús; Amasene, María; Arenaza Etxeberría, Lide; Tejada Garrido, Clara Isabel; Elejalde, E.; Azcárate Jiménez, Unai Xabier; Ruiz Sarrias, Oskitz; Sayar-Beristain, Onintza; García-Ramos, Amador; Martínez Labari, Cristina; Armendáriz Brugos, Cristina; Villanueva Larre, Arantxa; Ruiz, Jonatan R.; Cabeza Laguna, Rafael; Labayen Goñi, Idoia; Ciencias de la Salud; Osasun Zientziak; Institute of Smart Cities - ISC; Ingeniería Eléctrica, Electrónica y de Comunicación; Ingeniaritza Elektrikoa, Elektronikoa eta Telekomunikazio Ingeniaritza; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
    Background & aims: time-restricted eating (TRE) shows promise for weight loss and improving menopauserelated body composition and cardiometabolic health, but its effects on skeletal muscle tissue (SMT) in postmenopausal women are unknown. This study investigates the effects of three weight loss interventions over 12 weeks on SMT quantity, quality, function, and cardiometabolic health in postmenopausal women with overweight/obesity, with effects persistence evaluated at a 12-month follow-up. Methods and results: in this randomized controlled trial, 78 postmenopausal women (50–65 years; BMI 25–40 kg/m2; sedentary lifestyle; eating window ≥12 h/day; no severe metabolic impairments) will be recruited. Participants will be randomly assigned to one of three groups for 12 weeks: TRE, TRE + resistance training, or CR + resistance training. The TRE groups will reduce their eating window to 8 h and receive nutritional advice to adhere to a Mediterranean diet. The CR group will follow a personalized hypocaloric diet (− 500 kcal/day). Resistance training groups will perform supervised resistance training 3 times/week. Primary Outcome: Change in SMT quantity measured by MRI at baseline and after 12 weeks. Secondary Outcomes: intermuscular adipose tissue (IMAT), strength, power, body weight and composition, and cardiometabolic risk factors. Conclusion: this study will illustrate the effects of TRE and TRE combined with resistance exercise compared with the currently recommended obesity-lifestyle treatment on SMT quantity, quality, function, and cardiometabolic markers. The results will offer insights into dietary strategies to combat obesity and metabolic diseases without increasing sarcopenia risk in postmenopausal women, a sparsely studied and particularly affected population.
  • PublicationOpen Access
    Perceived quality of life is related to a healthy lifestyle and related outcomes in spanish children and adolescents: The physical activity, sedentarism, and obesity in spanish study
    (MDPI, 2023) Ródenas-Munar, Marina; Monserrat-Mesquida, Margalida; Gómez, Santiago F.; Wärnberg, Julia; Medrano Echeverría, María; González Gross, Marcela; Gusi, Narcís; Aznar, Susana; Marín-Cascales, Elena; González Valeiro, Miguel A.; Serra-Majem, Lluis; Pulgar, Susana; Segú, Marta; Fitó, Montserrat; Torres, Silvia; Benavente-Marín, Juan C.; Labayen Goñi, Idoia; Zapico, Augusto G.; Sánchez-Gómez, Jesús; Jiménez-Zazo, Fabio; Alcaraz, Pedro E.; Sevilla-Sánchez, Marta; Herrera-Ramos, Estefanía; Schröder, Helmut; Bouzas, Cristina; Tur, Josep A.; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
    Background: Maintaining a healthy lifestyle is crucial for safeguarding the well-being and quality of life perception, appropriate growth, and development of children and adolescents, while also mitigating the risk of future adult-onset diseases. Objective: To assess associations between perceived quality of life and healthy lifestyle and related outcomes in Spanish children and adolescents. Methods: Cross-sectional analysis of 8–16-year-old children and adolescents (n = 3534) were included in the nationwide study of Physical Activity, Sedentarism, and Obesity in Spanish Youth (PASOS). Data were collected through (1) questionnaires on health-related quality of life (HRQoL), healthy lifestyle outcomes (dietary intake, physical fitness, sleep, and screen time), and (2) anthropometric measurements for weight status assessment. Data were analysed by logistic regression, using the health-related quality of life (HRQoL) as the grouping variable. Results: Participants with a lower HRQoL were those with a lower adherence to the MedDiet and lower achievement of the recommended daily intake of fruit and vegetables. They were also less likely to follow the recommendations for screen time and sleep (with the exception of the weekend) compared to participants with a higher HRQoL. Participants with a lower HRQoL showed a lower healthy weight status and poorer physical fitness than those with a higher HRQoL. Conclusions: Healthy eating habits, healthy weight status (normal weight), appropriate sleep time, physical fitness, and limited screen time play a crucial role in the perceived quality of life in children and adolescents.
  • PublicationOpen Access
    Associations between the adherence to the Mediterranean diet and cardiorespiratory fitness with total and central obesity in preschool children: the PREFIT project
    (Springer, 2018) Labayen Goñi, Idoia; Arenaza Etxeberría, Lide; Medrano Echeverría, María; García, Natalia; Cadenas-Sánchez, Cristina; Ortega, Francisco B.; Ciencias de la Salud; Osasun Zientziak
    Purpose: Early recognition of risk factors associated with overweight/obesity is animportant 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 thenorth 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.
  • PublicationOpen Access
    Walkability and socio-economic status in relation to walking, playing and sports practice in a representative Spanish sample of youth: the PASOS study
    (Public Library of Science, 2024) Aznar, Susana; Jiménez-Zazo, Fabio; Romero-Blanco, Cristina; Gómez, Santiago F.; Homs, Clara; Wärnberg, Julia; Medrano Echeverría, María; Gusi, Narcís; González Gross, Marcela; Marín-Cascales, Elena; González Valeiro, Miguel A.; Serra-Majem, Lluis; Terrados, Nicolás; Tur, Josep A.; Segú, Marta; Lassale, Camille; Colom, Antoni; Labayen Goñi, Idoia; Sánchez-Gómez, Jesús; Alcaraz, Pedro E.; Sevilla-Sánchez, Marta; Zapico, Augusto G.; Herrera-Ramos, Estefanía; Pulgar, Susana; Bibiloni, María del Mar; Sistac-Sorigué, Clara; Schröder, Helmut; Molina-García, Javier; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
    Purpose Physical activity (PA) provides multiple health-related benefits in children and adolescents, however, at present, the majority of young people are insufficiently physically active. The aim of this study was to evaluate if neighborhood walkability and/or socio-economic status (SES) could affect the practice of walking, play outdoors and sports practice in a representative sample of Spanish children and adolescents. Methods A sample of 4092 youth (aged 8-16 years old) from 245 primary and secondary schools in 121 localities from each of the 17 Spanish autonomous communities participated in the study. Walk Score was used to evaluate walkability of the neighborhood and household income was used as an indicator of SES. A 7-item self-reported validated questionnaire, was used to assess PA levels, and in a subsample of 10% of the participants, randomly selected from the entire sample, PA was objectively measured by accelerometers. Results Youth from more walkable areas reported more minutes walking per day compared with those from less walkable neighborhoods (51.4 vs 48.8 minutes, respectively). The lowest average minutes spent in playing outdoors was found among participants from low-SES and low-walkable neighborhoods. Neighborhood SES influenced on the participation in team sports during the weekend, being this participation higher in high SES neighborhoods. Conclusion Providing high walkable environments seems a good strategy to promote PA regardless SES levels. It seems that improving the walkability is a key component to partially overcome the SES inequalities, especially in urban areas with low SES. High-SES environments can offer better sports facilities and more organized physical activities than low-SES ones.
  • PublicationOpen Access
    A sociodemographic, anthropometric and lifestyle-based prediction score for screening children with overweight and obesity for hepatic steatosis: the HEPAKID index
    (Wiley, 2021) Osés Recalde, Maddi; Medrano Echeverría, María; Galbete Jiménez, Arkaitz; Arenaza Etxeberría, Lide; Ruiz, Jonatan R.; Sánchez-Valverde, Félix; Ortega, Francisco B.; Labayen Goñi, Idoia; Ciencias de la Salud; Osasun Zientziak
    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.
  • PublicationOpen Access
    Nutritional status and physical performance using handgrip and SPPB tests in hospitalized older adults
    (Elsevier, 2021) Amasene, María; Besga, Ariadna; Medrano Echeverría, María; Urquiza, Miriam; Rodríguez Larrad, Ana; Tobalina, Ignacio; Barroso, Julia; Irazusta, Jon; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
    Background & aims: Malnutrition and poor physical performance are highly prevalent within hospitalized older adults, and both have in common the loss of muscle mass. Likewise, there is growing interest in identifying markers of physical performance, other than just measuring muscle mass, that might be useful for managing malnutrition. This study aimed to (i) characterize the physical condition of hospitalized older adults in comparison to previously published reference percentile values of same age adults and (ii) to examine the association between the nutritional status and physical performance of older inpatients. Methods: A total of 604 inpatients (age 84.3 ± 6.8 years, 50.3% women) participated in this cross-sectional study. Patients were assessed for nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF)) and physical performance (handgrip strength and the Short Physical Performance Battery (SPPB)). Results: During hospitalization, 65.7% of the inpatients were at risk of malnutrition or malnourished. More than a half of the older inpatients were unfit (≤P25) for handgrip strength (52.0%) and SPPB total score (86.3%) as well as for two of its subtests, gait speed (86.7%) and 5 times sit-to-stand (91.1%) tests. Patients' nutritional status was significantly associated with better physical performance within all tests (all p < 0.001), as their nutritional status improved so did their physical performance (all p for trend <0.001). Hence, being at risk of malnutrition or malnourished significantly increased the likelihood for being classified as unfit according to handgrip strength (OR: 1.466, 95% CI: 1.045–2.056), SPPB total score (OR: 2.553, 95% CI: 1.592–4.094) and 4-m walking test (OR: 4.049, 95% CI: 2.469–6.640) (all p < 0.05), and as frail (OR: 4.675, 95% CI: 2.812–7.772) according to the SPPB frailty threshold (p < 0.001). Conclusions: This study reinforces the use of handgrip strength and SPPB, as well as its subtests (gait speed and 5 times sit-to-stand tests), in hospitalized older adults as alternative measures of muscle mass for malnutrition management. Hence, it seems that risk of malnutrition or malnutrition assessed by MNA-SF might help to predict poor physical performance in older inpatients.
  • PublicationOpen Access
    Understanding the association of intrapancreatic fat deposition with adiposity and components of metabolic syndrome in children and adolescents: a systematic review and meta-analysis
    (Elsevier, 2025-05-06) Izquierdo Rodríguez, Claudia; Cadenas-Sánchez, Cristina; Santos Martín, José Luis; Ruiz, Jonatan R.; Medrano Echeverría, María; Martínez Vizcaíno, Vicente; Goran, Michael I.; Labayen Goñi, Idoia; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
    Background: Intrapancreatic fat deposition is associated with increased cardiovascular risk in adults, but the association is less clear in children. Our goal in this work was therefore to conduct a systematic review and meta-analysis of the associations between intrapancreatic fat deposition with adiposity and components of metabolic syndrome in children and adolescents. Methods: Systematic searches were conducted in MEDLINE, Web of Science, and Scopus from database inception to January 11, 2025 (registration number: CRD42022374159). Random-effects meta-analysis was performed to obtain pooled correlations estimates of the association of intrapancreatic fat deposition with various adiposity related outcomes (i.e., overall/central adiposity and specific fat depots; primary outcome) and cardiometabolic risk factors (i.e., glycaemic traits, insulin resistance/sensitivity, insulin secretion surrogates, plasma lipids, and blood pressure; secondary outcomes). Risk of bias and the quality of evidence were evaluated. Findings: We identified a total of 252 studies, of which 15 unique studies (N = 1261 participants, mean age ranged 10.6–17.7 years, 44.4% females) were eligible for meta-analysis. Magnetic resonance imaging-measured intrapancreatic fat deposition showed a small to medium positive significant association with adiposity (n = 53 studies, r = 0.24 [95% CI:0.19; 0.29], I2 = 61.5%), impaired glycaemic traits and insulin sensitivity (n = 11 studies, r = 0.15 [95% CI:0.03; 0.26], I2 = 58.9%), and HDL levels (n = 7 studies, pooled r = 0.11 [95% CI: 0.01; 0.20], I2 = 0%), and increased blood pressure (n = 6 studies, pooled r = 0.15 [95% CI: 0.05; 0.25], I2 = 0%). Interpretation: Intrapancreatic fat deposition may increase the risk of cardiometabolic disturbances in children. Therefore, it requires more attention in clinical research as an early indicator of ectopic fat deposition, insulin resistance and metabolic syndrome. Longitudinal studies are necessary to understand the temporal dynamics of these associations and to determine the long-term impact of intrapancreatic fat deposition on the risk of developing type 2 diabetes and cardiovascular diseases.
  • PublicationOpen Access
    Effects of a family-based lifestyle intervention plus supervised exercise training on abdominal fat depots in children with overweight or obesity: a secondary analysis of a nonrandomized clinical trial
    (American Medical Association, 2022) Cadenas-Sánchez, Cristina; Cabeza Laguna, Rafael; Idoate, Fernando; Osés Recalde, Maddi; Medrano Echeverría, María; Villanueva Larre, Arantxa; Arenaza Etxeberría, Lide; Sanz Muñoz, Aritz; Ortega, Francisco B.; Ruiz, Jonatan R.; Labayen Goñi, Idoia; Ciencias de la Salud; Ingeniería Eléctrica, Electrónica y de Comunicación; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Institute of Smart Cities - ISC; Osasun Zientziak; Ingeniaritza Elektrikoa, Elektronikoaren eta Telekomunikazio Ingeniaritzaren
    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.