Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3-15 Years.

BACKGROUND: Reference values of ferritin and transferrin for European children do not exist. OBJECTIVE: We aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15-y-old children based on cohort data and to investigate determinants of iron status. METHODS: A total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. RESULTS: The age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 µg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: ß = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: ß = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 µg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. CONCLUSIONS: Age-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.

Factors affecting continuous participation in follow-up evaluations during a lifestyle intervention programme for type 2 diabetes prevention: The Feel4Diabetes-study.

AIMS: Community- and school-based lifestyle interventions are an efficient method of preventing type 2 diabetes in vulnerable populations. Many participants, however, fail to complete the necessary follow-ups. We investigated factors affecting the continuous participation in follow-up evaluations during the Feel4Diabetes-study, a multilevel intervention programme implemented across Europe. METHODS: Socioeconomic, sociodemographic and clinical factors were assessed for 2702 participants within six participating countries: Bulgaria and Hungary (low-to-middle-income countries, LMIC), Belgium and Finland (high-income countries, HIC) and Greece and Spain (high-income countries under austerity measures, HICAM). RESULTS: Statistically significant differences were detected with respect to sex, control group, education level, employment status, BMI and blood pressure measurements (systolic and diastolic blood pressure). Post hoc analysis revealed significant differences within socioeconomic regions. Higher levels of education were associated with significantly lower attrition in HIC (p < 0.05) and HICAM (p < 0.001), higher employment status was associated with lower attrition in HICAM (p < 0.001) and being female was associated with lower attrition in LMIC (p < 0.001). Surprisingly, the intervention group exhibited higher-than-expected attrition in HIC (p < 0.001) and HICAM (p = 0.003), and lower attrition in LMIC (p = 0.007). When tested together in the same multivariable predictive model, all sociodemographic and socioeconomic variables along with higher BMI retained their statistical significance, while systolic and diastolic blood pressure failed to remain significant. CONCLUSIONS: Key socioeconomic and sociodemographic factors along with BMI play a significant role in determining continuous participation in follow-up evaluations during school- and community-based intervention programmes.

Physical activity in relation to metabolic health and obesity: The Feel4Diabetes study.

AIM: To examine physical activity levels in association with metabolic health and estimate the stability of metabolically healthy obese (MHO) phenotypes over a 2-year period. METHODS: In total, 2848 men and women from families at risk of the development of diabetes were recruited. Participants were classified as obese or non-obese and metabolic health was defined using five existing definitions. Physical activity was estimated with the International Physical Activity Questionnaire and pedometers. RESULTS: Prevalence of the MHO phenotype varied among definitions (0% to 20.2%). Overall, the MHO were more active than the metabolically unhealthy obese (MUO). Daily sitting hours (odds ratio [OR] = 1.055, 95% confidence interval [CI]: 1.009-1.104) and daily steps (per 500; OR = 0.934, 95% CI: 0.896-0.973) were remarkable predictors of metabolic health in individuals with obesity; and likewise, in individuals without obesity. After 2 years, 44.1% of baseline MHO adults transitioned to MUO, while 84.0% of the MUO at baseline remained at the same phenotype. Although physical activity was not a major determinant in phenotype transitioning, daily steps were associated with the maintenance of metabolic health over time in the non-obese group. CONCLUSION: A universally accepted definition for MHO is needed. Being physically active can contribute to a metabolically healthy profile even in the presence of obesity; still, MHO is a transient condition and physical activity alone may not be an adequate factor for its maintenance.

The role of psychosocial well-being and emotion-driven impulsiveness in food choices of European adolescents.

BACKGROUND: It is unclear whether a hypothetical intervention targeting either psychosocial well-being or emotion-driven impulsiveness is more effective in reducing unhealthy food choices. Therefore, we aimed to compare the (separate) causal effects of psychosocial well-being and emotion-driven impulsiveness on European adolescents' sweet and fat propensity. METHODS: We included 2,065 participants of the IDEFICS/I.Family cohort (mean age: 13.4) providing self-reported data on sweet propensity (score range: 0 to 68.4), fat propensity (range: 0 to 72.6), emotion-driven impulsiveness using the UPPS-P negative urgency subscale, and psychosocial well-being using the KINDLR Questionnaire. We estimated, separately, the average causal effects of psychosocial well-being and emotion-driven impulsiveness on sweet and fat propensity applying a semi-parametric doubly robust method (targeted maximum likelihood estimation). Further, we investigated a potential indirect effect of psychosocial well-being on sweet and fat propensity mediated via emotion-driven impulsiveness using a causal mediation analysis. RESULTS: If all adolescents, hypothetically, had high levels of psychosocial well-being, compared to low levels, we estimated a decrease in average sweet propensity by 1.43 [95%-confidence interval: 0.25 to 2.61]. A smaller effect was estimated for fat propensity. Similarly, if all adolescents had high levels of emotion-driven impulsiveness, compared to low levels, average sweet propensity would be decreased by 2.07 [0.87 to 3.26] and average fat propensity by 1.85 [0.81 to 2.88]. The indirect effect of psychosocial well-being via emotion-driven impulsiveness was 0.61 [0.24 to 1.09] for average sweet propensity and 0.55 [0.13 to 0.86] for average fat propensity. CONCLUSIONS: An intervention targeting emotion-driven impulsiveness, compared to psychosocial well-being, would be marginally more effective in reducing sweet and fat propensity in adolescents.

Genotyping of Toxoplasma gondii in domestic animals from Campeche, México, reveals virulent genotypes and a recombinant ROP5 allele.

Toxoplasma gondii has at least 318 genotypes distributed worldwide, and tropical regions usually have greater genetic diversity. Campeche is a state located in the southeastern region of México and has favourable climate conditions for the replication and dissemination of this protozoan, similar to those in South American countries where broad genetic diversity has been described. Thus, in this study, 4 T. gondii isolates were obtained from tissues of stray dogs and free-range chickens in Campeche, México, and were genotyped by Mn-PCR-RFLP with 10 typing markers (SAG1, altSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) and 5 virulence markers (CS3, ROP16, ROP17, ROP18 and ROP5) to provide new information about the distribution and virulence prediction of T. gondii genotypes. Two isolates of T. gondii genotype #116 and 2 of genotype #38 were obtained from stray dogs and chickens, respectively. The parasite load found in these species was between <50 and more than 35 000 tachyzoites per mg of tissue. Virulence marker genotyping revealed a recombinant 1&3 ROP5 RFLP pattern in 2 ToxoDB #116 isolates with no prediction of virulence in a murine model, while in the 2 ToxoDB #38 isolates, the ROP18/ROP5 combination predicted high virulence. Considering all the typed markers, there is a predominance of type I and III alleles, as constantly reported for the isolates characterized in various regions of México. It is crucial to determine their phenotype to corroborate the genetic virulence profile of the T. gondii isolates obtained in this study.

Cardiometabolic risk assessment: A school-based study in Brazilian adolescent.

BACKGROUND AND AIMS: Recently, new indices combining routine and low-cost anthropometric and biochemical measurements have emerged. Among them, the visceral adiposity index (VAI) and lipid accumulation product (LAP) are being investigated for the prediction of altered blood pressure (BP) and insulin resistance (IR). Therefore, this study aimed to evaluate whether visceral adiposity index (VAI) and height-corrected lipid accumulation product (HLAP) are predictors of cardiometabolic risk in Brazilian adolescents. METHODS AND RESULTS: Data were obtained from the Cardiovascular Risk in Adolescents (ERICA) study, a cross-sectional, national, multicenter, school-based survey conducted between 2013 and 2014 in Brazil. The sample consisted of 37,815 adolescents aged 12-17 years of both genders attending the last 3 years of elementary or secondary school from public and private schools located in 273 municipalities with more than 100,000 inhabitants. A Poisson regression was performed to verify associations between VAI and HLAP indices and the presence of altered BP and IR according to sex. In addition, receiver operating characteristic curve (ROC) analysis was applied to compare the predictive ability and determine the cut-off points of the VAI and HLAP indices in identifying cardiometabolic risk obtained by altered BP and IR. The prevalences of altered BP and IR were 24.49 % (95 % confidence interval [CI]: 23.14-25.87) and 24.22 % (95 % CI: 22.70-25.80), respectively. CONCLUSIONS: The VAI and HLAP indices are good predictors of cardiometabolic risk in Brazilian adolescents. HLAP showed better performance in identifying insulin resistance in males.

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.

Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Addressing chronic diseases: a comparative study of policies towards type-2 diabetes and hypertension in selected European countries.

BACKGROUND: Type-2 diabetes (T2D) and hypertension (HTN) are two of the most prevalent non-communicable diseases (NCDs): they both cause a relevant number of premature deaths worldwide and heavily impact the national health systems. This study illustrates the impact of HTN and T2D in four European countries (Albania, Bulgaria, Greece and Spain) and compares their policies towards the monitoring and management of HTN and T2D and the prevention of NCDs as a whole. This analysis is conducted throughout the DigiCare4You Project (H2020)-which implements an innovative solution involving digital tools for the prevention and management of T2D and HTN. METHODS: The analysis is implemented through desk research, and it is enriched with additional information directly provided by the local coordinators in the four countries, by filling specific semi-structured forms. RESULTS: The countries exhibit significant differences in the prevalence of HTN and T2D and available policies and programs targeted to these two chronic conditions. Each country has implemented strategies for HTN and T2D, including prevention initiatives, therapeutic guidelines, educational programs and children's growth monitoring programs. However, patient education on proper disease management needs improvement in all countries, registries about patients affected by HTN and T2D are not always available, and not all countries promoted acts to contain the increasing rates of risk factors related to NCDs. CONCLUSIONS: While political awareness of the risks associated with HTN, T2D and NCDs in general is growing, there is a collective need for countries to strengthen their policies for preventing and managing these chronic diseases.

Parental practices and children's lifestyle correlates of childhood overweight/obesity in Europe: The Feel4Diabetes study.

BACKGROUND: Parental influences on children's eating and physical activity (PA) and consequently on their weight are fundamental. The present study aimed to identify the predominant correlates of childhood overweight/obesity among a variety of parental practices and children's lifestyle indices in a large sample of children in Europe. METHODS: Families from low socio-economic status regions were recruited through schools, located in six European countries (Belgium, Finland, Greece, Spain, Bulgaria and Hungary). Seven thousand three hundred ninety-seven children 4-12 years old and their parents were selected using the FINDRISC-questionnaire. Parental practices assessed included parental role modelling, permissiveness and reward. Children's dietary intake and lifestyle behaviours were assessed through parent-reported questionnaires. RESULTS: Regarding parental practices, it was revealed that being sometimes (odds ratio [OR] = 1.26; 95% confidence interval [CI] = 1.10-1.43) or rarely (OR = 1.43; 95% CI = 1.21-1.69) physically active with the child was associated with greater overweight/obesity risk, whereas rare permission of computer/mobile/tablet (OR = 0.81; 95% CI = 0.67-0.98) and sometimes (OR = 0.77; 95% CI = 0.68-0.88) or rare (OR = 0.77; 95% CI = 0.66-0.91) reward with PA were associated with lower risk. Regarding children's lifestyle factors, consuming > 3 cups/week fresh fruit juices (OR = 1.28; 95% CI = 1.13-1.45), skipping breakfast (OR = 1.37; 95% CI = 1.17-1.61), absence of 1 h of daily PA (OR = 1.40; 95% CI = 1.24-1.58) and increased daily screen time (ST) (OR = 1.23; 95% CI = 1.09-1.39) were associated with greater overweight/obesity risk. All the variables were adjusted for maternal education, child's sex and age. CONCLUSIONS: These findings emphasize the necessity of family-centered approaches in health promotion and obesity prevention programs for children. Such programs should focus on parents as the primary role models in exerting positive influence and encouraging healthy eating habits, PA, and ST behaviors in their children, which in turn, may have a substantial impact on children's overall weight status.

van der Waals Materials for Overcoming Fundamental Limitations in Photonic Integrated Circuitry.

With the advance of on-chip nanophotonics, there is a high demand for high-refractive-index and low-loss materials. Currently, this technology is dominated by silicon, but van der Waals (vdW) materials with a high refractive index can offer a very advanced alternative. Still, up to now, it was not clear if the optical anisotropy perpendicular to the layers might be a hindering factor for the development of vdW nanophotonics. Here, we studied WS2-based waveguides in terms of their optical properties and, particularly, in terms of possible crosstalk distance. Surprisingly, we discovered that the low refractive index in the direction perpendicular to the atomic layers improves the characteristics of such devices, mainly due to expanding the range of parameters at which single-mode propagation can be achieved. Thus, using anisotropic materials offers new opportunities and novel control knobs when designing nanophotonic devices.

A Ca2+-Dependent Mechanism Boosting Glycolysis and OXPHOS by Activating Aralar-Malate-Aspartate Shuttle, upon Neuronal Stimulation.

Calcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In embryonic mouse cortical neurons using glucose as only fuel, activation by NMDA elicits a strong workload (ATP demand)-dependent on Na+ and Ca2+ entry, and stimulates glucose uptake, glycolysis, pyruvate and lactate production, and oxidative phosphorylation (OXPHOS) in a Ca2+-dependent way. We find that Ca2+ upregulation of glycolysis, pyruvate levels, and respiration, but not glucose uptake, all depend on Aralar/AGC1/Slc25a12, the mitochondrial aspartate-glutamate carrier, component of the malate-aspartate shuttle (MAS). MAS activation increases glycolysis, pyruvate production, and respiration, a process inhibited in the presence of BAPTA-AM, suggesting that the Ca2+ binding motifs in Aralar may be involved in the activation. Mitochondrial calcium uniporter (MCU) silencing had no effect, indicating that none of these processes required MCU-dependent mitochondrial Ca2+ uptake. The neuronal respiratory response to carbachol was also dependent on Aralar, but not on MCU. We find that mouse cortical neurons are endowed with a constitutive ER-to-mitochondria Ca2+ flow maintaining basal cell bioenergetics in which ryanodine receptors, RyR2, rather than InsP3R, are responsible for Ca2+ release, and in which MCU does not participate. The results reveal that, in neurons using glucose, MCU does not participate in OXPHOS regulation under basal or stimulated conditions, while Aralar-MAS appears as the major Ca2+-dependent pathway tuning simultaneously glycolysis and OXPHOS to neuronal activation.SIGNIFICANCE STATEMENT Neuronal activation increases cell workload to restore ion gradients altered by activation. Ca2+ is involved in matching increased workload with ATP production, but the mechanisms are still unknown. We find that glycolysis, pyruvate production, and neuronal respiration are stimulated on neuronal activation in a Ca2+-dependent way, independently of effects of Ca2+ as workload inducer. Mitochondrial calcium uniporter (MCU) does not play a relevant role in Ca2+ stimulated pyruvate production and oxygen consumption as both are unchanged in MCU silenced neurons. However, Ca2+ stimulation is blunt in the absence of Aralar, a Ca2+-binding mitochondrial carrier component of Malate-Aspartate Shuttle (MAS). The results suggest that Ca2+-regulated Aralar-MAS activation upregulates glycolysis and pyruvate production, which fuels mitochondrial respiration, through regulation of cytosolic NAD+/NADH ratio.

Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children's cohort.

AIMS/HYPOTHESIS: There is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution. METHODS: Genotyping was successful in 2825 children aged 2-14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15-P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin. RESULTS: A variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10-8). Two variants associated with low z-insulin (P15, p value <5×10-6) were located on the RBFOX1 and SH3RF3 genes. These genes have previously been associated with both metabolic traits and dementia phenotypes. While variants associated with P50 showed stable associations across the insulin spectrum, we found that associations with variants identified through GWA analyses of P15 and P85 varied across quantiles of log-insulin. CONCLUSIONS/INTERPRETATION: The above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker-disease associations.

Cardiometabolic risk profile among children with migrant parents and role of parental education: the IDEFICS/I.Family cohort.

BACKGROUND AND AIMS: Evidence shows that migrant children have a higher risk of developing obesity than those with native parents. We aimed to investigate the association between parental migration background and cardiometabolic health in children and adolescents in Europe. METHODS AND RESULTS: We included 8745 children aged 2-17 from the second follow-up of the European IDEFICS/I.Family cohort. Linear regression models were used to investigate the association between parental migration background (one or two migrant parent(s) vs native parents) and body mass index (BMI), metabolic syndrome (MetS) score and its individual components. Outcome variables were parametrized as age and sex-specific z-scores. We adjusted for age, sex, country, and parental education, and additionally for parental income, lifestyle including dietary factors, and maternal BMI. On average, children with two migrant parents had higher z-scores of BMI (+0.24 standard deviation (SD)) and MetS score (+0.30 SD) compared to those with native parents, whereas no significant differences were seen for children with one migrant parent. Associations were attenuated when controlling for maternal BMI and sports club activity. Parental education modified the associations with BMI and MetS z-scores such that they were more pronounced in children with low parental education. CONCLUSION: Children with two migrant parents were at higher risk for adverse cardiometabolic health compared to children with native parents, especially in families with low parental education. These associations were explained by lower physical activity and maternal body weight and encourages early intervention strategies by schools and communities.

Associations Between Eating Speed, Diet Quality, Adiposity, and Cardiometabolic Risk Factors.

OBJECTIVE: To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children. STUDY DESIGN: A cross-sectional study in 1371 preschool age children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the ß-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile. RESULTS: Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (ß, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (ß, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (ß, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (ß, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (ß, -0.5 points; 95% CI, -0.9 to -0.1 points). CONCLUSIONS: Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations.

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.

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.

Adherence to the EAT-Lancet sustainable reference diet and cardiometabolic risk profile: cross-sectional results from the ELSA-Brasil cohort study.

PURPOSE: The EAT-Lancet Commission released a reference sustainable diet to improve human health and respect the planetary boundaries. The Planetary Health Diet Index (PHDI) was developed with the purpose of evaluate the adherence to this reference diet. The aim of the present study was to evaluate the association between adherence to the EAT-Lancet diet with cardiometabolic risk profile. METHODS: We used the cross-sectional baseline data from 14,155 participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter ongoing cohort study. Dietary data were collected using a 114-item validated food frequency questionnaire. The PHDI was used to assess the adherence to the EAT-Lancet diet. It consists of 16 components and the total score can range from 0 to 150 points. Linear, logistic and quasi-Poisson regression models were built to evaluate the associations between PHDI and the outcomes. RESULTS: Individuals with higher adherence to EAT-Lancet diet (PHDI, 5th quintile) had lower values for systolic blood pressure (ß - 0.84; 95% CI - 1.66: - 0.01), diastolic blood pressure (ß - 0.70; 95% CI - 1.24: - 0.15), total cholesterol (ß - 3.15; 95% CI - 5.30: - 1.01), LDL-c (ß - 4.10; 95% CI - 5.97: -  2.23), and non-HDL-cholesterol (ß - 2.57; 95% CI - 4.62: - 0.52). No association was observed for HDL-c, triglycerides and HOMA-IR. CONCLUSIONS: Our results indicate that higher adherence to the EAT-Lancet diet is associated with lower levels of blood pressure, total cholesterol, LDL-c, and non-HDL-c.

Clinical and physical characteristics of thinness in adolescents: the HELENA study.

PURPOSE: Thinness in adolescence has not been studied as extensively as overweight or obesity. The aim of this study was to assess the prevalence, characteristics, and health impacts of thinness in a European adolescent population. METHODS: This study included 2711 adolescents (1479 girls, 1232 boys). Blood pressure, physical fitness, sedentary behaviors, physical activity (PA), and dietary intake were assessed. A medical questionnaire was used to report any associated diseases. A blood sample was collected in a subgroup of the population. Thinness and normal weight were identified using the IOTF scale. Thin adolescents were compared with adolescents of normal weight. RESULTS: Two hundred and fourteen adolescents (7.9%) were classified as being thin; the prevalence rates were 8.6% in girls and 7.1% in boys. Systolic blood pressure was significantly lower in adolescents with thinness. The age at the first menstrual cycle was significantly later in thin female adolescents than in those with normal weight. Upper-body muscular strength measured in performance tests and time spent in light PA were significantly lower in thin adolescents. The Diet Quality Index was not significantly lower in thin adolescents, but the percentage of adolescents who skipped breakfast was higher in adolescents with a normal weight (27.7% vs 17.1%). Serum creatinine level and HOMA-insulin resistance were lower and vitamin B12 level was higher in thin adolescents. CONCLUSIONS: Thinness affects a notable proportion of European adolescents with no physical adverse health consequences.

Relative validity of the Planetary Health Diet Index by comparison with usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet among European adolescents: the HELENA study.

PURPOSE: The EAT-Lancet Commission proposed an evidence-based global reference diet to improve human health within planetary boundaries. Recently, the Planetary Health Diet Index (PHDI) was developed based on the EAT-Lancet recommendations and validated among Brazilian adults. However, the relative validity of the PHDI in adolescents has yet to be assessed. Thus, we aimed to evaluate the relative validity of the PHDI in European adolescents. METHODS: We used cross-sectional data from 1804 adolescents (12.5-17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. The PHDI (0-150 points) was calculated based on dietary intake data from two non-consecutive 24-h dietary recalls. Associations between the PHDI and usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet were evaluated using multivariable-adjusted mixed-effects linear regression models. RESULTS: Higher PHDI score was associated with greater intakes of nutrients predominantly from plant-source foods, such as vegetable protein, vitamin E, and folate and with lower intake of nutrients predominately from animal-source foods, such as total and saturated fat, cholesterol, and animal protein. Furthermore, a higher PHDI score was also positively associated with plasma ß-carotene, vitamin C, vitamin D, folate, and ferritin concentrations, while negatively associated with trans-fatty acids concentration. Moreover, higher PHDI was related to a greater adherence to the Mediterranean dietary pattern. CONCLUSIONS: The PHDI showed good relative validity among adolescents in the HELENA study. Hence, future research should assess adherence to the PHDI and long-term health outcomes.