Open 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.
Open Access
European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network
(BMJ Publishing Group, 2023) Ortega, Francisco B.; Leskošek, Bojan; Blagus, Rok; Gil Cosano, José J.; Mäestu, Jarek; Tomkinson, Grant R.; Ruiz, Jonatan R.; Mäestu, Evelin; Starc, Gregor; Milanovic, Ivana; Tammelin, Tuija H.; Soric, Maroje; Scheuer, Claude; Carraro, Attilio; Kaj, Mónika; Csányi, Tamás; Sardinha, Luis B.; Lenoir, Matthieu; Emeljanovas, Arunas; Mieziene, Brigita; Sidossis, Labros S.; Pihu, Maret; Lovecchio, Nicola; Konstabel, Kenn; Tambalis, Konstantinos D.; Stefan, Lovro; Drenowatz, Clemens; Rubín, Lukáš; Gontarev, Seryozha; Castro Piñero, José; Vanhelst, Jérémy; O'Keeffe, Brendan; Veiga, Óscar L.; Gisladottir, Thordis; Sandercock, Gavin; Misigoj-Durakovic, Marjeta; Niessner, Claudia; Riso, Eva-María; Popovic, Stevo; Kuu, Saima; Chinapaw, Mai; Clavel, Iván; Labayen Goñi, Idoia; Dobosz, Janusz; Colella, Dario; Kriemler, Susi; Salaj, Sanja; Noriega, María José; Bös, Klaus; Sánchez López, Mairena; Lakka, Timo A.; Tabacchi, Garden; Novak, Dario; Ahrens, W.; Wedderkopp, Niels; Jurak, Gregor; Ciencias de la Salud; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Objectives (1) To develop reference values for health-related fitness in European children and adolescents aged 6-18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. Methods This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test-retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. Results A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu). Conclusion This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe.
Open Access
Association between UCP1, UCP2, and UCP3 gene polymorphisms with markers of adiposity in European adolescents: The HELENA study
(Wiley, 2019) Pascual Gamarra, José Miguel; Salazar-Tortosa, Diego; Martínez Téllez, Borja; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Manios, Yannis; Nova, Esther; Gesteiro, Eva; Moreno, Luis A.; Meirhaeghe, Aline; Ruiz, Jonatan R.; Osasun Zientziak; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD; Ciencias de la Salud
Aims: To examine the association between UCP1, UCP2, and UCP3 gene polymorphisms with adiposity markers in European adolescents and to test if there were gene interactions with objectively measured physical activity and adiposity. Methods: A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. A total of 18 polymorphisms in UCP1, UCP2, and UCP3 genes were genotyped. We measured weight, height, waist, and hip circumferences and triceps and subscapular skinfold thickness. Physical activity was objectively measured by accelerometry during 7 days. Results: The C allele of the UCP1 rs6536991 polymorphism was associated with a lower risk of overweight (odds ratio [OR]: T/C + C/C vs T/T) = 0.72; 95% confidence interval [CI]: 0.53-0.98; P = 0.034; false discovery rate [FDR] = 0.048). There was a significant interaction between UCP1 rs2071415 polymorphism and physical activity with waist-to-hip ratio (P = 0.006; FDR = 0.026). Adolescents who did not meet the physical activity recommendations (less than 60 min/day of moderate to vigorous physical activity) and carrying the C/C genotype had higher waist-to-hip ratio (+ 0.067; 95% CI, 0.028-0.106; P = 0.003), while no differences across genotypes were observed in adolescents meeting the recommendations. Conclusions: Two UCP1 polymorphisms were associated with adiposity in European adolescents. Meeting the daily physical activity recommendations may overcome the effect of the UCP1 rs2071415 polymorphism on obesity-related traits.
Open Access
Single nucleotide polymorphisms of ADIPOQ gene associated with cardiovascular disease risk factors in European adolescents: the HELENA study
(Wolters Kluwer, 2020) Salazar-Tortosa, Diego; Pascual Gamarra, José Miguel; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Béghin, Laurent; Michels, Nathalie; González Gross, Marcela; Manios, Yannis; Lambrinou, Christina-Paulina; Moreno, Luis A.; Meirhaeghe, Aline; Castillo, Manuel J.; Ruiz, Jonatan R.; Ciencias de la Salud; Osasun Zientziak
Objectives: Cardiovascular diseases (CVDs) are responsible of 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. Aims of present research are to examine the association of ADIPOQ gene polymorphisms with cardiovascular disease risk factors in European adolescents. Methods: A total of 14 polymorphisms in the ADIPOQ gene were genotyped in 1057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. We measured serum lipids and a CVD risk score, along with weight, height, triceps, and subscapular skinfold thickness, leptin, insulin and other markers of glucose regulation. Results: The rs822393, rs822395 and rs7649121 polymorphisms of ADIPOQ gene were significantly associated with several CVD risk factors [i.e. high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, SBP and CVD risk score] in European adolescents. We also found an association of the TGAAGT ADIPOQ haplotype (rs822393, rs16861210, rs822395, rs822396, rs12495941 and rs7649121) with HDL-C and ApoA1 levels. Conclusion: Several individual polymorphisms (rs822393, rs822395 and rs7649121) and a haplotype of ADIPOQ gene were significantly associated with cardiovascular disease risk factors in European adolescents.
Open Access
Interaction effect of the Mediterranean diet and an obesity genetic risk score on adiposity and metabolic syndrome in adolescents: the HELENA study
(MDPI, 2020) Seral-Cortes, Miguel; Sabroso-Lasa, Sergio; Miguel Etayo, Carmen de; González Gross, Marcela; Gesteiro, Eva; Molina Hidalgo, Cristina; Henauw, Stefaan de; Erhardt, Éva; Manios, Yannis; Karaglani, Eva; Widhalm, Kurt; Kafatos, Antonios; Béghin, Laurent; Meirhaeghe, Aline; Salazar-Tortosa, Diego; Ruiz, Jonatan R.; Moreno, Luis A.; Esteban, Luis Mariano; Labayen Goñi, Idoia; Ciencias de la Salud; Osasun Zientziak
Obesity and metabolic syndrome (MetS) are worldwide major health challenges. The Mediterranean diet (MD) is associated with a better cardiometabolic profile, but these beneficial effects may be influenced by genetic variations, modulating the predisposition to obesity or MetS. The aim was to assess whether interaction effects occur between an obesity genetic risk score (obesity-GRS) and the MD on adiposity and MetS in European adolescents. Multiple linear regression models were used to assess the interaction effects of an obesity-GRS and the MD on adiposity and MetS and its components. Interaction effects between the MD on adiposity and MetS were observed in both sex groups (p < 0.05). However, those interaction effects were only expressed in a certain number of adolescents, when a limited number of risk alleles were present. Regarding adiposity, a total of 51.1% males and 98.7% females had lower body mass index (BMI) as a result of higher MD adherence. Concerning MetS, only 9.9% of males with higher MD adherence had lower MetS scores. However, the same effect was observed in 95.2% of females. In conclusion, obesity-related genotypes could modulate the relationship between MD adherence and adiposity and MetS in European adolescents; the interaction effect was higher in females than in males.
Open Access
Association between CNTF polymorphisms and adiposity markers in European adolescents
(Mosby/Elsevier, 2020) Pascual Gamarra, José Miguel; Salazar-Tortosa, Diego; Labayen Goñi, Idoia; Rupérez, Azahara I.; Censi, Laura; Béghin, Laurent; Michels, Nathalie; González Gross, Marcela; Manios, Yannis; Lambrinou, Christina-Paulina; Moreno, Luis A.; Meirhaeghe, Aline; Castillo, Manuel J.; Ruiz, Jonatan R.; Ciencias de la Salud; Osasun Zientziak
Objective: To examine the association between polymorphisms of the ciliary neurotrophic factor gene (CNTF) and total and central adiposity markers in adolescents. Study design: This cross-sectional study involved 1057 European adolescents aged 12-18 years enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. Five polymorphisms of CNTF were genotyped, and the weight, height, waist and hip circumference, and triceps and subscapular skinfold thickness of the subjects were measured and recorded. Results: The T allele of rs2509914, the C allele of rs2515363, and the G allele of rs2515362 were significantly associated (after Bonferroni correction) with higher values for several adiposity markers under different inheritance models. The CNTF CCGGA haplotype (rs2509914, rs17489568, rs2515363 rs1800169, and rs2515362) was also significantly associated with lower body mass index, waist circumference, waist/height ratio, and waist/hip ratio values compared with the TCCGG haplotype under several inheritance models. Conclusions: Three polymorphisms—rs2509914, rs2515363, and rs2515362—and the CCGGA haplotype of CNTF were significantly associated with adiposity in European adolescents. These results suggest the potential role of CTNF in the development of obesity-related phenotypes.
Open Access
Adherence to the Mediterranean diet in metabolically healthy and unhealthy overweight and obese European adolescents: the HELENA study
(Springer, 2019) Arenaza Etxeberría, Lide; Huybrechts, Inge; Ortega, Francisco B.; Ruiz, Jonatan R.; Henauw, Stefaan de; Manios, Yannis; Marcos, Ascensión; Julián, Cristina; Widhalm, Kurt; Labayen Goñi, Idoia; Institute on Innovation and Sustainable Development in Food Chain - ISFOOD
Purpose To examine the adherence to the Mediterranean dietary pattern (MDP) in metabolically healthy overweight or obese (MHO) and metabolically unhealthy obese (MUO) European adolescents. Methods In this cross-sectional study, 137 overweight/obese adolescents aged 12-17 years old from the HELENA study were included. Height, weight, waist circumference and skinfold thickness were measured and body mass index and body fat percent were calculated. Systolic and diastolic blood pressure, glucose, HDL cholesterol, triglycerides and cardiorespiratory fitness (20 m shuttle run test) were measured. MHO and MUO phenotypes were categorized following the Jolliffe and Janssen criteria. Two non-consecutive 24 h recalls were used for dietary intake assessment and the adherence to the MDP was calculated using the Mediterranean dietary pattern score (MDP score) (range 0-9). Results A total of 45 (22 girls) adolescents (32.8%) were categorized as MHO. The adherence to the MDP was significantly higher in MHO than in MUO adolescents regardless of age, sex, body fat percentage, energy intake and center (MDP score: 4.6 +/- 1.6 vs. 3.9 +/- 1.5, p = 0.036), but this difference became non-significant after further adjustment for cardiorespiratory fitness. Participants who had a low adherence to the MDP (MDP score <= 4) had a higher likelihood of having MUO phenotype regardless of sex, age, energy intake, center and body fat percentage (OR 2.2; 95% CI 1.01-4.81, p = 0.048). Conclusions Adherence to the MDP might be beneficial to maintain metabolic health in overweight/obese adolescents, yet cardiorespiratory fitness seems to play a key role on the metabolic phenotype.