Open Access
Development of a prediction protocol for the screening of metabolic associated fatty liver disease in children with overweight or obesity
(Wiley, 2022) Osés Recalde, Maddi; Cadenas-Sánchez, Cristina; Medrano Echeverría, María; Galbete Jiménez, Arkaitz; Miranda Ferrúa, Emiliano; Ruiz, Jonatan R.; Sánchez-Valverde, Félix; Ortega, Francisco B.; Cabeza Laguna, Rafael; Villanueva Larre, Arantxa; Idoate, Fernando; Labayen Goñi, Idoia; Osasun Zientziak; Institute of Smart Cities - ISC; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud; Gobierno de Navarra / Nafarroako Gobernua
Background: the early detection and management of children with metabolic associ-ated fatty liver disease (MAFLD) is challenging. Objective: to develop a non-invasive and accurate prediction protocol for the identi-fication of MAFLD among children with overweight/obesity candidates to confirma-tory diagnosis. Methods: a total of 115 children aged 8–12 years with overweight/obesity, rec-ruited at a primary care, were enrolled in this cross-sectional study. The external vali-dation 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 reso-nance imaging (MRI). Fasting blood biochemical parameters were measured, and25 candidates’ single nucleotide polymorphisms (SNPs) were determined. Variablespotentially associated with the presence of MAFLD were included in a multivariatelogistic regression. Results: children with MAFLD (36%) showed higher plasma triglycerides (TG),insulin, homeostasis model assessment ofinsulin resistance (HOMA-IR), alanineaminotransferase (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). Threebiochemical- and/or SNPs-based predictive models were developed, showingstrong discriminatory capacity (AUC-ROC: 0.708–0.888) but limited diagnosticperformance (sensitivity 67%–82% and specificity 63%–69%). A prediction proto-col 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.
Open Access
Effects of exercise on bone marrow adipose tissue in children with overweight/obesity: role of liver fat
(Oxford University Press, 2024-08-07) Labayen Goñi, Idoia; Cadenas-Sánchez, Cristina; Idoate, Fernando; Gracia-Marco, Luis; Medrano Echeverría, María; Alfaro-Magallanes, Víctor Manuel; Alcántara Alcántara, Juan Manuel; Rodríguez Vigil, Beatriz; Osés Recalde, Maddi; Ortega, Francisco B.; Ruiz, Jonatan R.; Cabeza Laguna, Rafael; Ingeniería Eléctrica, Electrónica y de Comunicación; Ingeniaritza Elektrikoa, Elektronikoa eta Telekomunikazio Ingeniaritza; Agronomía, Biotecnología y Alimentación; Agronomia, Bioteknologia eta Elikadura; Ciencias de la Salud; Osasun Zientziak; Institute of Smart Cities - ISC; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Gobierno de Navarra / Nafarroako Gobernua
Context: Exercise reduces adiposity, but its influence on bone marrow fat fraction (BMFF) is unknown; nor is it known whether a reduction in liver fat content mediates this reduction. Objectives: This work aimed to determine whether incorporating exercise into a lifestyle program reduces the lumbar spine (LS) BMFF and to investigate whether changes in liver fat mediate any such effect.Methods Ancillary analysis of a 2-arm, parallel, nonrandomized clinical trial was conducted at primary care centers in Vitoria-Gasteiz, Spain. A total of 116 children with overweight/obesity 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]). The compared interventions consisted of a family-based lifestyle program (two 90-minute sessions/month) and the same program plus supervised exercise (three 90-minute sessions/week). The primary outcome examined was the change in LS-BMFF between baseline and 22 weeks, as estimated by magnetic resonance imaging. The effect of changes in hepatic fat on LS-BMFF were also recorded.Results Mean weight loss difference between groups was 1.4 +/- 0.5 kg in favor of the exercise group. Only the children in the exercise group experienced a reduction in LS-BMFF (effect size [Cohen d] -0.42; CI, -0.86 to -0.01). Importantly, 40.9% of the reductions in LS-BMFF were mediated by changes in percentage hepatic fat (indirect effect: beta=-0.104; 95% CI, -0.213 to -0.019). The effect of changes in hepatic fat on LS-BMFF was independent of weight loss.Conclusion The addition of exercise to a family-based lifestyle program designed to reduce cardiometabolic risk improves bone health by reducing LS-BMFF in children with overweight or obesity. This beneficial effect on bone marrow appears to be mediated by reductions in liver fat.
Open 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.
Open Access
Associations of dietary energy density with body composition and cardiometabolic risk in children with overweight and obesity: role of energy density calculations, under-reporting energy intake and physical activity
(Cambridge University Press, 2019) Gómez Bruton, Alejandro; Arenaza Etxeberría, Lide; Medrano Echeverría, María; Mora González, José; Cadenas-Sánchez, Cristina; Migueles, Jairo H.; Muñoz-Hernández, Victoria; Merchán Ramírez, Elisa; Martínez Ávila, Wendy D.; Maldonado, José; Osés Recalde, Maddi; Tobalina, Ignacio; Gracia-Marco, Luis; Vicente Rodríguez, Germán; Ortega, Francisco B.; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8-12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0 019), body fat percentage (P=0 005), abdominal fat (P=0 008) and fat mass index (P=0 018), while EDSL was positively associated with body fat percentage (P=0 008) and fat mass index (P=0 026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.
Open 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.
Open Access
Association of breakfast quality and energy density with cardiometabolic risk factors in overweight/obese children: role of physical activity
(MDPI, 2018) Arenaza Etxeberría, Lide; Muñoz-Hernández, Victoria; Medrano Echeverría, María; Osés Recalde, Maddi; Amasene, María; Merchán Ramírez, Elisa; Cadenas-Sánchez, Cristina; Ortega, Francisco B.; Ruiz, Jonatan R.; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
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 (= -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.
Open 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.
Open Access
Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: the role of cardiorespiratory fitness
(Wiley, 2023) Cadenas-Sánchez, Cristina; Medrano Echeverría, María; Villanueva Larre, Arantxa; Cabeza Laguna, Rafael; Idoate, Fernando; Osés Recalde, Maddi; Rodríguez Vigil, Beatriz; Álvarez de Eulate, Natalia; Alberdi Aldasoro, Nerea; Ortega, Francisco B.; 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
Objectives: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under- studied. Therefore, the aims of this study were: (i) to examine the differ-ences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. Methods: A total of 114 children with overweight/obesity (10.6 ±1.1 years, 62 girls) were included. Children were classified as MHO (n=68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. Results: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference =12.4%– 25.8%, all p<0.035). MUO- unfit had more VAT and ASAT content than those MUO- fit and MHO- fit (difference =34.8%– 45.3%, all p<0.044). MUO- unfit shows also greater IMAAT fat fraction than those MUO- fit and MHO- fit peers (difference =16.4%– 13.9% respectively, all p≤0.001). In addition, MHO- unfit presented higher IMAAT fat fraction than MHO- fit (difference =13.4%, p<0.001). MUO- unfit presented higher psoas fat fraction than MHO- fit (difference =29.1%, p=0.008). Conclusions: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.
Open Access
Influence of physical activity on bone mineral content and density in overweight and obese children with low adherence to the Mediterranean dietary pattern
(MDPI, 2018) Muñoz-Hernández, Victoria; Arenaza Etxeberría, Lide; Gracia-Marco, Luis; Medrano Echeverría, María; Merchán Ramírez, Elisa; Martínez Ávila, Wendy D.; Osés Recalde, Maddi; Ruiz, Jonatan R.; Ortega, Francisco B.; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
The objective of the present cross-sectional study was to examine the associations of physical activity and the adherence to the Mediterranean dietary pattern (MDP) with bone mineral content (BMC) and density (BMD) in children with overweight and obesity. A total of 177 (n = 80 girls) children with overweight and obesity aged 8 to 12 years old participated in the study. Both BMC and BMD were assessed by Dual-Energy X-ray absorptiometry. Dietary patterns were assessed by the KIDMED questionnaire and two 24-hour recalls. Physical activity was assessed by accelerometers for 7 consecutive days (24 hours/day). Low adherence to the MDP was observed in 82.4% of participants. Higher physical activity levels (of at least moderate intensity) and lower sedentary time were significantly associated with BMC and BMD in children with low adherence to the MDP (all p < 0.05). No associations were observed between physical activity and BMC and BMD in children with high adherence to the MDP. In conclusion, engaging in moderate to vigorous physical activity and reducing the time spent in sedentary behavior might be particularly beneficial for improving bone health in overweight or obese children with poor adherence to the Mediterranean dietary pattern.
Open Access
Hepatic fat content and bone mineral density in children with overweight/obesity
(Springer Nature, 2018) Labayen Goñi, Idoia; Ruiz, Jonatan R.; Arenaza Etxeberría, Lide; Medrano Echeverría, María; Tobalina, Ignacio; Gracia-Marco, Luis; Ortega, Francisco B.; Rodríguez Vigil, Beatriz; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud
Objectives: To examine the influence of non-alcoholic fatty liver disease (NAFLD) and hepatic fat content on bone mineral density (BMD), and to investigate whether the relationship between NAFLD and BMD is independent of lifestyle factors related to BMD. Methods: Hepatic fat content (magnetic resonance imaging), BMD, lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry), moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and vitamin D intake (two 24 h recalls) were measured in 115 children with overweight/obesity aged 10.6 +/- 1.1 years old. Result: Children with NAFLD had lower BMD than children without NAFLD regardless of sex, puberty stage, lean mass index, fat mass, MVPA, and calcium and vitamin D intake (0.89 +/- 0.01 vs. 0.93 +/- 0.01 g/cm(2) for NAFLD and non-NAFLD, respectively, P < 0.01). Higher hepatic fat content was significantly associated with lower BMD regardless of confounders (adjusted P < 0.05). Conclusions: Findings of the current study suggest that hepatic fat accumulation is associated with decreased BMD independently of adiposity, and regardless of those lifestyle factors closely related to bone mineral accrual in children. These results may have implication in the clinical management of children with overweight/obesity given the high prevalence of pediatric NAFLD.