Effectiveness and process evaluation in obesity and type 2 diabetes prevention programs in children: a systematic review and meta-analysis

Background: Obesity in children is one of the most severe public health challenges of the current century and Type 2 Diabetes Mellitus (T2DM) frequency is also escalating. More so, the importance of process evaluation (PE) in complex interventions is increasingly recognized. The present review, aims to identify the effectiveness in terms of body composition parameters in a generation of articles to prevent obesity and T2DM in children. We hypothesise that those studies reporting PE applying the latest implementation guidelines suggested by the researchers would potentially show positive changes in body composition compared to those not reporting it. Additionally, we will evaluate the implementation degree of PE in those articles considering it and describe the PE subcomponents. Lastly, we aim to assess the intervention target used and its results. Methods: A literature review was performed in parallel by 2 independent reviewers. A final number of 41 studies were selected for inclusion criteria. Results: Meta-analysis of BMI and zBMI found non-significant effects of the proposed interventions. Sub-group analysis revealed only a significant effect in studies which performed PE. Moreover, PE was reported in 42% effective studies and 57% non-effective studies. Fidelity and satisfaction were the most implemented PE subcomponents, although there was a generally low grade of PE use (7/41). The highest proportion of effectiveness (83%) was shown in interventions of physical activity alone while the intervention most used was 3-arm target (diet, PA and BS). Conclusions: Overall, obesity and T2DM prevention studies included in this review are not effective in terms of BMI and zBMI. Those studies performing PE reported to be effective in terms of BMI, while studies not reporting PE did not have positive results in terms of BMI and zBMI. In addition, none of the intervention studies included all PE indicators and most studies, which included PE in their interventions, did not provide full report of the PE components, according to the guidelines used for the present review. PROSPERO registration number: CRD42018093667

Association between PTPN1 polymorphisms and obesity-related phenotypes in European adolescents: influence of physical activity

Background: To study the associations of Protein Tyrosine Phosphatase-N1 (PTPN1) polymorphisms with obesity-related phenotypes in European adolescents, and the influence of physical activity on these relationships. Methods: Five polymorphisms of PTPN1 were genotyped in 1057 European adolescents (12–18 years old). We measured several phenotypes related to obesity, such as adiposity markers, and biochemical and clinical parameters. Physical activity was objectively measured by accelerometry. Results: The T, A, T, T and G alleles of the rs6067472, rs10485614, rs2143511, rs6020608 and rs968701 polymorphisms, respectively, were associated with lower levels of obesity-related phenotypes (i.e., body mass index, body fat percentage, hip circumference, fat mass index, systolic blood pressure and leptin) in European adolescents. In addition, the TATTG haplotype was associated with lower body fat percentage and fat mass index compared to the AACCA haplotype. Finally, when physical activity levels were considered, alleles of the rs6067472, rs2143511, rs6020608 and rs968701 polymorphisms were only associated with lower adiposity in active adolescents. Conclusions: PTPN1 polymorphisms were associated with adiposity in European adolescents. Specifically, alleles of these polymorphisms were associated with lower adiposity only in physically active adolescents. Therefore, meeting the recommendations of daily physical activity may reduce obesity risk by modulating the genetic predisposition to obesity. Impact: - Using gene-phenotype and gene*environment analyses, we detected associations between polymorphisms of the Protein Tyrosine Phosphatase-N1 (PTPN1) gene and obesity-related phenotypes, suggesting a mechanism that can be modulated by physical activity. - This study shows that genetic variability of PTPN1 is associated with adiposity, while physical activity seems to modulate the genetic predisposition. - This brings insights about the mechanisms by which physical activity positively influences obesity

Mediterranean diet, screen-time-based sedentary behavior and their interaction effect on adiposity in European adolescents: The HELENA study

Childhood obesity is a worldwide epidemic. Mediterranean diet (MD) is inversely associated with childhood obesity, but the interaction with other environmental factors, such screen time, might influence the health benefits of a high MD adherence in adolescents. The aim of the present study was to assess whether an association between MD and screen time exists in European adolescents. Moreover, we also explored whether sedentary time has a modulatory effect on the association between MD and adiposity. Adherence to the MD (24 h recalls), screen time (questionnaire), pubertal development, body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were evaluated in 2053 adolescents (54.7% females), aged 12.5–17.5 years. In females, MD adherence was associated with lower BMI and FMI only when they were exposed to less than 338 min/day of screen time (81.8% of females); MD adherence was also associated with lower WC only when females were exposed to less than 143 min/day of screen time (31.5% of females). No significant MD-screen time interaction was observed in males. In conclusion, screen-time-based sedentary behaviours had a modulatory effect in the association between MD adherence and adiposity in European female adolescents

Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11–19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual’s predisposition to overweight/obesity in European adolescents.European Commission FOOD-CT-2005-007034HELENA projectSpanish Ministry of Economy and Competitiveness RYC-2010-05957 RYC2011-09011Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn)Iberus Talent Pre-doctoral fellowships under the European Union 801586Instituto de Salud Carlos III CB15/0004

The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study

Background Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. Methods A total of 972 adolescents (51.3% females), aged 12.5–17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p < .05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. Results The uGRS and wGRS were significantly associated with ALT (p < .001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. Conclusions Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents

Mediterranean Diet, Screen-Time-Based Sedentary Behavior and Their Interaction Effect on Adiposity in European Adolescents: The HELENA Study

Childhood obesity is a worldwide epidemic. Mediterranean diet (MD) is inversely associated with childhood obesity, but the interaction with other environmental factors, such screen time, might influence the health benefits of a highMD adherence in adolescents. The aimof the present studywas to assess whether an association between MD and screen time exists in European adolescents. Moreover, we also explored whether sedentary time has a modulatory effect on the association between MD and adiposity. Adherence to the MD (24 h recalls), screen time (questionnaire), pubertal development, body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were evaluated in 2053 adolescents (54.7% females), aged 12.5–17.5 years. In females, MD adherence was associated with lower BMI and FMI only when they were exposed to less than 338 min/day of screen time (81.8% of females);MD adherence was also associated with lowerWC only when females were exposed to less than 143 min/day of screen time (31.5% of females). No significantMD-screen time interaction was observed in males. In conclusion, screen-time-based sedentary behaviours had a modulatory effect in the association between MD adherence and adiposity in European female adolescents.Iberus Talent Pre-doctoral fellowships 2018, under the European Union's H2020 research and innovation programme under Marie Sklodowska-Curie grant 801586Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, CIBERObn ISCIII-CB15/00043European Commission FOOD-CT-2005-007034HELENA projectSpanish Ministry of Economy and Competitiveness RYC-2010-05957 RYC-2011-09011Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn

Mediterranean diet and genetic determinants of obesity and metabolic syndrome in european children and adolescents

Childhood obesity and metabolic syndrome (MetS) are multifactorial diseases influenced by genetic and environmental factors. The Mediterranean Diet (MD) seems to modulate the genetic predisposition to obesity or MetS in European adults. The FTO gene has also been shown to have an impact on the MD benefits to avoid obesity or MetS. Since these interaction effects have been scarcely analyzed in European youth, the aim was to describe the gene¿MD interplay, analyzing the impact of the genetic factors to reduce the obesity and MetS risk through MD adherence, and the MD impact in the obesity and MetS genetic profile. From the limited evidence on gene¿MD interaction studies in European youth, a study showed that the influence of high MD adherence on adiposity and MetS was only observed with a limited number of risk alleles; the gene¿MD interplay showed sex-specific differences, being higher in females. Most results analyzed in European adults elucidate that, the relationship between MD adherence and both obesity and MetS risk, could be modulated by obesity genetic variants and vice versa. Further research is needed, to better understand the inter-individual differences in the association between MD and body composition, and the integration of omics and personalized nutrition considering MD.Miguel Seral-Cortes has received funding from the Iberus Talent Pre-doctoral fellowships 2018, under the European Union's H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No 801586

Effect of Mediterranean Diet Adherence and Its Interaction with Genetic Susceptibility to Obesity on Adiposity in European Children: The IDEFICS/I.Family Study

The Mediterranean Diet (MD) has been associated with a better adiposity profile in different cohorts of European children. However, these beneficial effects might be influenced by genetic variations, which could potentially modulate the MD–adiposity association. Objectives: To investigate if higher adherence to the MD, or any of the MD food groups, is associated with lower adiposity during youth. Also, to observe the degree by which the adherence to the MD or any of the MD food groups could modulate the genetic susceptibility to obesity, in relation to adiposity. Methods: Design: Cohort study with three measurement surveys: baseline (T0), follow-up 1 (T1), and follow-up 2 (T3), between 2007 and 2014. Setting: The pan-European IDEFICS/I.Family cohort. Participants: 3098 children aged 2–16 years were genotyped. A total of 1907 participants at time measurement 3 (T3) were included, with complete information in all parameters of interest. Outcome measures: body mass index (BMI) and waist circumference (WC). A 7-item Mediterranean Diet Score (MDS) to assess the degree of MD adherence, and a genome-wide polygenic risk score (PRS) for BMI previously built within the IDEFICS/I.Family consortium, from a previous GWAS to capture obesity risk. Statistical analysis: In T3, multiple linear regressions to test MD–adiposity and MD-food-groups–adiposity associations, adjusted by age, sex, parental education, genetic susceptibility to obesity, population stratification, region of residence, screen sedentary time (SST), and physical activity. Then, the same models were used to estimate gene x diet effects, based on the PRS x MD adherence. Results: No associations were found between MDS and BMI or WC adiposity markers (p-value 0.26, B 0.10). In terms of food groups, higher vegetable consumption was inversely associated to BMI (p-value < 0.01, B −0.01) and WC (p-value 0.01, B −0.02), although no gene x vegetables interaction effects were found (BMI p-value 0.43, B < 0.01; WC p-value 0.49, B 0.01). Age and SST were also significantly associated to BMI (p-value 0.01, B −0.12; p-value < 0.01, B 0.02), and only SST to WC (p-value 0.03, B 0.05), respectively. Conclusions: Higher consumption of vegetables might be associated with lower obesity, irrespective of their obesity genetic risk