Efficacy of different 8 h time-restricted eating schedules on visceral adipose tissue and cardiometabolic health: A study protocol.

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.

Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

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.

Medical imaging in the assessment of cardiovascular disease risk.

PURPOSE OF REVIEW: The prevalence of obesity has exponentially increased during the past years. The assessment of human adipose tissue distribution enables the identification of diverse ectopic adipose tissue depots, and helps to explain its relationship with cardiovascular health status. In this review, we summarize the current methods used in the assessment of human adipose tissue distribution, and we discuss the relationship between ectopic adipose tissue distribution and the risk of developing cardiovascular diseases and metabolic complications. RECENT FINDINGS: The reference instruments to assess human adipose tissue distribution nowadays are the computed tomography and the magnetic resonance imaging (MRI). Today, MRI is the preferred imaging technique and enables the measurement of variations in the distribution of body adipose tissue among different phenotypes and individuals. This technique has helped to better understand the relationship between different ectopic adipose tissue depots and its relationship with cardiometabolic health among individuals. SUMMARY: Although body composition can be assessed by simple techniques, these calculations can provide erroneous results and conclusions, requiring complex interpretations when diverse metabolic situations are concomitantly engaged. Contrarily, medical imaging techniques (e.g. MRI) enables to objectively and unbiasedly measure changes that may occur during longitudinal studies (e.g. pharmacological drug interventions).

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.

Reproducibility of the energy metabolism response to an oral glucose tolerance test: influence of a postcalorimetric correction procedure.

PURPOSE: Metabolic flexibility (MetF), which is a surrogate of metabolic health, can be assessed by the change in the respiratory exchange ratio (RER) in response to an oral glucose tolerance test (OGTT). We aimed to determine the day-to-day reproducibility of the energy expenditure (EE) and RER response to an OGTT, and whether a simulation-based postcalorimetric correction of metabolic cart readouts improves day-to-day reproducibility. METHODS: The EE was assessed (12 young adults, 6 women, 27 ± 2 years old) using an Omnical metabolic cart (Maastricht Instruments, Maastricht, The Netherlands) after an overnight fast (12 h) and after a 75-g oral glucose dose on 2 separate days (48 h). On both days, we assessed EE in 7 periods (one 30-min baseline and six 15-min postprandial). The ICcE was performed immediately after each recording period, and capillary glucose concentration (using a digital glucometer) was determined. RESULTS: We observed a high day-to-day reproducibility for the assessed RER (coefficients of variation [CV] < 4%) and EE (CVs < 9%) in the 7 different periods. In contrast, the RER and EE areas under the curve showed a low day-to-day reproducibility (CV = 22% and 56%, respectively). Contrary to our expectations, the postcalorimetric correction procedure did not influence the day-to-day reproducibility of the energy metabolism response, possibly because the Omnical's accuracy was ~ 100%. CONCLUSION: Our study demonstrates that the energy metabolism response to an OGTT is poorly reproducible (CVs > 20%) even using a very accurate metabolic cart. Furthermore, the postcalorimetric correction procedure did not influence the day-to-day reproducibility. Trial registration NCT04320433; March 25, 2020.

Association of meal timing with body composition and cardiometabolic risk factors in young adults.

PURPOSE: To investigate the association of meal timing with body composition and cardiometabolic risk factors in young adults. METHODS: In this cross-sectional study participated 118 young adults (82 women; 22 ± 2 years old; BMI: 25.1 ± 4.6 kg/m2). Meal timing was determined via three non-consecutive 24-h dietary recalls. Sleep outcomes were objectively assessed using accelerometry. The eating window (time between first and last caloric intake), caloric midpoint (local time at which ≥ 50% of daily calories are consumed), eating jetlag (variability of the eating midpoint between non-working and working days), time from the midsleep point to first food intake, and time from last food intake to midsleep point were calculated. Body composition was determined by DXA. Blood pressure and fasting cardiometabolic risk factors (i.e., triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and insulin resistance) were measured. RESULTS: Meal timing was not associated with body composition (p > 0.05). The eating window was negatively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.348, ß = - 0.605; R2 = 0.234, ß = - 0.508; all p ≤ 0.003). The time from midsleep point to first food intake was positively related to HOMA-IR and cardiometabolic risk score in men (R2 = 0.212, ß = 0.485; R2 = 0.228, ß = 0.502; all p = 0.003). These associations remained after adjusting for confounders and multiplicity (all p ≤ 0.011). CONCLUSIONS: Meal timing seems unrelated to body composition in young adults. However, a longer daily eating window and a shorter time from midsleep point to first food intake (i.e., earlier first food intake in a 24 h cycle) are associated with better cardiometabolic health in young men. CLINICAL TRIAL REGISTRATION: NCT02365129 ( https://www. CLINICALTRIALS: gov/ct2/show/NCT02365129?term=ACTIBATE&draw=2&rank=1 ).

Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: The role of cardiorespiratory fitness.

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 differences 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.

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.

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.

Effect of Moderate Versus Vigorous Exercise Intensity on Body Composition in Young Untrained Adults: The Activating Brown Adipose Tissue Through Exercise (ACTIBATE) Randomized Controlled Trial.

The present study aimed to investigate the effect of a 24-week aerobic + resistance training programs at moderate versus vigorous intensity on body composition, and the persistence of the changes after a 10-month free-living period, in young untrained adults. This report is based on a secondary analysis from the activating brown adipose tissue through exercise (ACTIBATE) single-center unblinded randomized controlled trial. A total of 144 young adults (65.6% women) aged 18-25 years were randomly allocated to three different groups: (a) aerobic + resistance exercise training program based on the international physical activity recommendations at vigorous intensity (Ex-Vigorous group), (b) at moderate intensity (Ex-Moderate group), and (c) control group (no exercise). Body composition outcomes were determined by a dual-energy X-ray absorptiometry scanner. Both Ex-Vigorous and Ex-Moderate decreased body weight, fat mass, and visceral adipose tissue mass in a similar manner (all p < .04). After a 10-month free-living period, these parameters returned to baseline levels in both exercise groups (all ps < .03). No differences between the exercise groups and the control group were noted in lean mass changes (all ps > .1). A 24-week aerobic + resistance training intervention based on the international physical activity recommendations was enough to improve body weight, fat mass, and visceral adipose tissue mass in untrained young adults, independently of the exercise intensity (moderate vs. vigorous).

Interplay of physical activity and genetic variants of the endothelial lipase on cardiovascular disease risk factors.

BACKGROUND: The aim of this study was to investigate the association of endothelial lipase gene (LIPG) polymorphisms with cardiovascular disease (CVD) risk factors in adolescents and their interaction with physical activity. METHODS: Six polymorphisms of LIPG were genotyped in 1057 European adolescents (12-18 years old) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. CVD risk factors related to lipid profile, blood pressure, adiposity and glucose regulation were recorded. Physical activity was objectively measured by accelerometry. RESULTS: The major C allele of rs2000813, the minor T allele of rs2276269 and the minor G allele of rs9951026 were associated with lower levels of several CVD risk factors related to lipid profile. We also found a significant association of the TTACA LIPG haplotype (rs2000812, rs2000813, rs8093249, rs2276269 and rs9951026) with higher concentrations of low-density cholesterol and apolipoprotein B. Finally, the interaction between physical activity and the polymorphisms rs2000813, rs2276269 and rs9951026 had a significant influence on several CVD risk factors. CONCLUSIONS: LIPG polymorphisms were significantly associated with CVD risk factors in European adolescents. Interestingly, alleles of these polymorphisms were associated with a better cardiovascular profile in physically active adolescents only. High physical activity may reduce the development of CVD, modulating its genetic risk. IMPACT: Using gene-phenotype and gene × environment analyses, we detected associations between the endothelial lipase gene and cardiovascular risk factors, along with interactions with physical activity. This study shows that physical activity may modulate the influence of LIPG gene on cardiovascular risk in adolescents. These results bring insights into the mechanisms by which physical activity positively influences CVD in adolescents.

Associations of fitness and physical activity with specific abdominal fat depots in children with overweight/obesity.

OBJECTIVES: To examine the relationship between physical fitness and physical activity (PA) with specific abdominal fat depots and their potential implications for cardiometabolic risk and insulin resistance (IR) in children with overweight/obesity. MATERIALS AND METHODS: A total of 116 children with overweight/obesity (10.7 ± 1.1 year, 54% girls) participated in the study. Abdominal visceral (VAT), subcutaneous (ASAT), and intermuscular abdominal adipose tissue (IMAAT) were assessed by magnetic resonance imaging. The cardiometabolic risk (MetS) score and the insulin resistance homeostasis model assessment (HOMA-IR) were calculated. Health-related physical fitness components (treadmill test, and 20 m shuttle run, handgrip, standing broad jump and 4 × 10 m tests) were evaluated, and PA was measured (accelerometry). Children were categorized as fit or unfit for each specific fitness test, and as active or inactive. RESULTS: Higher VAT, ASAT, and IMAAT were associated with higher MetS score and HOMA-IR (all p < 0.02). A better performance in all fitness tests and total and vigorous PA were strongly associated with lower VAT (all p < 0.04), ASAT (all p < 0.005), and IMAAT (all p < 0.005). Fit or active children had lower VAT, ASAT, and IMAAT (all p < 0.03) than their unfit or inactive counterparts. CONCLUSION: These results reinforce the importance of having adequate fitness and PA levels to reduce abdominal fat accumulation in children. Given that VAT, ASAT, and IMAAT are associated with higher risk of developing cardiovascular diseases and type 2 diabetes, the improvement of physical fitness by the promotion of PA should be goals of lifestyle interventions for improving health in children with overweight/obesity.

Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity.

AIM: Adipokines seem to play a role in bone morphogenesis, although this also depends on the mechanical forces applied to the skeleton. The aim was to assess the relationships of resting leptin and adiponectin with bone parameters and whether high muscular fitness levels affect these relationships in children with overweight or obesity. METHODS: This cross-sectional study took part from 2014 to 2016 in Granada, Spain. Participants were recruited from University Hospitals, and we also used advertisements in local media and school contacts in the city. Adipokines were analysed in plasma. Muscular fitness was assessed by one repetition maximum in bench and leg press tests. Dual-energy X-ray absorptiometry was used to measure bone parameters. RESULTS: We included 84 children (10.0 ± 1.2y; 63% boys) in this analysis. Leptin was negatively associated with lumbar spine bone mineral content (ß = -0.162, p = 0.053). No significant interaction was found for muscular fitness. Simple slope estimates suggested that children performing more than 133.3 kg in leg press test ameliorated the negative association between leptin and lumbar spine bone mineral content. CONCLUSION: Leptin levels were negatively associated with lumbar spine bone mineral content in children with overweight or obesity. A high muscular fitness at the lower body could counteract this association.

Validity, reliability, and calibration of the physical activity unit 7 item screener (PAU-7S) at population scale.

BACKGROUND: Validation of self-reported tools, such as physical activity (PA) questionnaires, is crucial. The aim of this study was to determine test-retest reliability, internal consistency, and the concurrent, construct, and predictive validity of the short semi-quantitative Physical Activity Unit 7 item Screener (PAU-7S), using accelerometry as the reference measurement. The effect of linear calibration on PAU-7S validity was tested. METHODS: A randomized sample of 321 healthy children aged 8-16 years (149 boys, 172 girls) from the nationwide representative PASOS study completed the PAU-7S before and after wearing an accelerometer for at least 7 consecutive days. Weight, height, and waist circumference were measured. Cronbach alpha was calculated for internal consistency. Test-retest reliability was determined by intra-class correlation (ICC). Concurrent validity was assessed by ICC and Spearman correlation coefficient between moderate to vigorous PA (MVPA) derived by the PAU-7S and by accelerometer. Concordance between both methods was analyzed by absolute agreement, weighted kappa, and Bland-Altman statistics. Multiple linear regression models were fitted for construct validity and predictive validity was determined by leave-one-out cross-validation. RESULTS: The PAU-7S overestimated MVPA by 18%, compared to accelerometers (106.5 ± 77.0 vs 95.2 ± 33.2 min/day, respectively). A Cronbach alpha of 0.76 showed an acceptable internal consistency of the PAU-7S. Test-retest reliability was good (ICC 0.71 p < 0.001). Spearman correlation and ICC coefficients of MVPA derived by the PAU-7S and accelerometers increased from 0.31 to 0.62 and 0.20 to 0.62, respectively, after calibration of the PAU-7S. Between-methods concordance improved from a weighted kappa of 0.24 to 0.50 after calibration. A slight reduction in ICC, from 0.62 to 0.60, yielded good predictive validity. Multiple linear regression models showed an inverse association of MVPA with standardized body mass index (ß - 0.162; p < 0.077) and waist to height ratio (ß - 0.010; p < 0.014). All validity dimensions were somewhat stronger in boys compared to girls. CONCLUSION: The PAU-7S shows a good test-retest reliability and acceptable internal consistency. All dimensions of validity increased from poor/fair to moderate/good after calibration. The PAU-7S is a valid instrument for measuring MVPA in children and adolescents. TRIAL REGISTRATION: Trial registration number ISRCTN34251612 .

Relationships between diet and basal fat oxidation and maximal fat oxidation during exercise in sedentary adults.

BACKGROUND AND AIMS: To study the relationships between different dietary factors (i.e., energy, macronutrient and fatty acid intake, food group consumption, and dietary pattern) and basal fat oxidation (BFox) and maximal fat oxidation during exercise (MFO) in sedentary adults. METHOD AND RESULTS: A total of 212 (n = 130 women; 32.4 ± 15.1 years) sedentary healthy adults took part in the present study. Information on the different dietary factors examined was gathered through a food frequency questionnaire and three nonconsecutive 24 h recalls. Energy and macronutrient intakes and food consumption were then estimated and dietary patterns calculated. BFox and MFO were measured by indirect calorimetry following standard procedures. Our study shows that dietary fiber intake was positively associated with BFox after taking into consideration the age, sex, and energy intake. A significant positive association between nut consumption and BFox was observed, which became nonsignificant after taking into consideration the age and energy intake. Fat intake and the dietary quality index (DQI), and the DQI for the Mediterranean diet were positively associated with MFO, which was attenuated after taking sex, age, and energy intake into consideration. CONCLUSION: A higher dietary fiber intake and fat intake are associated with higher BFox and MFO, respectively, in sedentary adults. CLINICAL TRIALS: ClinicalTrials.gov, ID: NCT02365129 (https://clinicaltrials.gov/ct2/show/study/NCT02365129) & ID: NCT03334357 (https://clinicaltrials.gov/ct2/show/NCT03334357).

Cardiorespiratory fitness, muscular strength, and obesity in adolescence and later chronic disability due to cardiovascular disease: a cohort study of 1 million men.

AIMS: Cardiorespiratory fitness, muscular strength, and obesity in adulthood are risk factors for cardiovascular disease (CVD). However, little is known regarding the associations of these risk factors, already in adolescence, with later disability due to chronic CVD. Hence, we investigated associations of cardiorespiratory fitness, muscular strength, and body mass index (BMI) in adolescence with later chronic disability due to specific causes of CVD disability (i.e. cerebrovascular disease, ischaemic heart disease and heart failure). METHODS AND RESULTS: This population-based cohort study included 1 078 685 male adolescents (16-19 years) from the Swedish military conscription register from 1972 to 1994. Cardiorespiratory fitness (bicycle ergometer test), muscular strength (knee extension strength), and BMI were measured during the conscription examination. Information about disability pension due to CVD was retrieved from the Social Insurance Agency during a mean follow-up of 28.4 years. Cardiorespiratory fitness was strongly and inversely associated with later risk of chronic CVD disability for all investigated causes. The association was particularly strong for ischaemic heart diseases (hazard ratio 0.11, 95% confidence interval 0.05-0.29 for highest vs. lowest fitness-quintiles). Furthermore, overweight/obesity were associated with CVD disability for all investigated causes. Conversely, associations of muscular strength with CVD disability were generally weak. CONCLUSIONS: This study provides evidence for associations between low levels of cardiorespiratory fitness and obesity with later risk of chronic disability due to CVD. Preventive actions may begin at young ages and include promotion of cardiorespiratory fitness and healthy body weight.

Association between CNTF Polymorphisms and Adiposity Markers in European Adolescents.

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.

Association of UCP1, UCP2 and UCP3 gene polymorphisms with cardiovascular disease risk factors in European adolescents: the HELENA study.

BACKGROUND: Cardiovascular diseases (CVDs) are responsible for 31% of all deaths worldwide. Genetic predisposition to CVDs in adolescents remains largely unknown. The aim of this study was to examine the association of UCP1, UCP2 and UCP3 gene polymorphisms with CVD risk factors in European adolescents. METHOD: A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the HELENA study. A total of 18 polymorphisms of UCP1, UCP2 and UCP3 genes were genotyped. We measured serum total cholesterol, high-density lipoprotein,low-density lipoprotein, ApoA1, ApoB, leptin, triglycerides, glucose, insulin and blood pressure, and calculated HOMA (homeostatic model assessment), Quantitative Insulin Sensitivity Check Index (QUICKI) and a CVD risk score. RESULTS: The G allele of UCP2 rs2735572 and T allele of UCP2 rs17132534 were associated with higher diastolic blood pressure (P = 0.001; false discovery rate [FDR] = 0.009 and P = 8e-04; FDR = 0.009, respectively). We observed that the AATAG haplotype of UCP1 was associated with higher serum ApoB/ApoA1 (P = 0.008; FDR = 0.031) and ApoB levels (P = 0.008; FDR = 0.031). Moreover, the ACC haplotype of UCP3 was associated with a higher CVD risk score (P = 0.0036; FDR = 0.01). CONCLUSIONS: Two UCP2 polymorphisms and haplotypes of UCP1 and UCP3 were associated with CVD risk factors. These findings suggest that UCPs may have a role in the development of CVD already in adolescents.

Inflammatory markers and bone mass in children with overweight/obesity: the role of muscular fitness.

OBJECTIVES: To examine which inflammatory markers are associated with bone mass and whether this association varies according to muscular fitness in children with overweight/obesity. METHODS: Plasma interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor, vascular endothelial growth factor A (VEGF), and C-reactive protein were analyzed in 55 children aged 8-11 years. A muscular fitness score was computed. Bone mineral content (BMC) of the total body-less head (TBLH) and lumbar spine (LS) were assessed using dual-energy x-ray absorptiometry. RESULTS: IL-6 (ß = -0.136) and VEGF (ß = -0.099) were associated with TBLH BMC, while TNF-α (ß = -0.345) and IL-1ß (ß = 0.212) were associated with LS BMC (P < 0.05). The interaction effect of muscular fitness showed a trend in the association of VEGF with TBLH BMC (P = 0.122) and TNF-α with LS BMC (P = 0.057). Stratified analyses by muscular fitness levels showed an inverse association of VEGF with TBLH BMC (ß = -0.152) and TNF-α with LS BMC (ß = -0.491) in the low-fitness group, while no association was found in the high-fitness group. CONCLUSION: IL-6, VEGF, TNF-α, and IL-1ß are significantly associated with bone mass. Higher muscular fitness may attenuate the adverse effect of high VEGF and TNF-α on bone mass.

Prevalence of severe/morbid obesity and other weight status and anthropometric reference standards in Spanish preschool children: The PREFIT project.

BACKGROUND: Childhood obesity has become a major health problem in children under the age of 5 years. Providing reference standards would help paediatricians to detect and/or prevent health problems related to both low and high levels of body mass and to central adiposity later in life. Therefore, the aim of this study was to examine the prevalence of different weight status categories and to provide sex- and age-specific anthropometry reference standards for Spanish preschool children. METHODS: A total of 3178 preschool children (4.59±0.87 years old) participated in this study. Prevalence of different degrees of obesity (mild, severe, and morbid) and other weight status categories were determined. RESULTS: Reference standards were obtained. Prevalence of overweight and obese preschool children in the Spanish population ranged from 21.4 to 34.8%. Specifically, the obesity prevalence was 3.5, 1.2, and 1.3% of these subjects were categorized as mild, severe, and morbid obese. Sex- and age-specific reference standards for anthropometric parameters are provided for every 0.25 years (i.e. every trimester of life). CONCLUSION: Our results show a high prevalence of overweight/obese preschoolers. The provided sex- and age-specific anthropometric reference standards could help paediatricians to track and monitor anthropometric changes at this early stage in order to prevent overweight/obesity.