A longitudinal causal graph analysis investigating modifiable risk factors and obesity in a European cohort of children and adolescents.

Childhood obesity is a complex disorder that appears to be influenced by an interacting system of many factors. Taking this complexity into account, we aim to investigate the causal structure underlying childhood obesity. Our focus is on identifying potential early, direct or indirect, causes of obesity which may be promising targets for prevention strategies. Using a causal discovery algorithm, we estimate a cohort causal graph (CCG) over the life course from childhood to adolescence. We adapt a popular method, the so-called PC-algorithm, to deal with missing values by multiple imputation, with mixed discrete and continuous variables, and that takes background knowledge such as the time-structure of cohort data into account. The algorithm is then applied to learn the causal structure among 51 variables including obesity, early life factors, diet, lifestyle, insulin resistance, puberty stage and cultural background of 5112 children from the European IDEFICS/I.Family cohort across three waves (2007-2014). The robustness of the learned causal structure is addressed in a series of alternative and sensitivity analyses; in particular, we use bootstrap resamples to assess the stability of aspects of the learned CCG. Our results suggest some but only indirect possible causal paths from early modifiable risk factors, such as audio-visual media consumption and physical activity, to obesity (measured by age- and sex-adjusted BMI z-scores) 6 years later.

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.

Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

OBJECTIVE: To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. METHODS: Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. RESULTS: The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. CONCLUSIONS: Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Digital media exposure and cognitive functioning in European children and adolescents of the I.Family study.

The digital environment can pose health risks through exposure to unhealthy content. Yet, little is known about its relation to children's cognitive functioning. This study investigates the association between digital media (DM) exposure and children's cognitive functioning. This cross-sectional study is based on examinations of children aged 8-18 years (N = 8673) of the I.Family cohort (2013-2014). Exposure to television, computer, smartphone and internet was self-reported (hours/day). Media multitasking (MMT) was defined as simultaneous use of computers with other digital or non-screen-based activities. Standard instruments were used to assess cognitive inflexibility (score: 0-39), decision-making ability (- 100 to + 100) and impulsivity (12-48). Adjusted regression coefficients and 99.9%CIs were calculated by generalized linear mixed-effects models. In total, 3261 participants provided data for impulsivity, 3441 for cognitive inflexibility and 4046 for decision-making. Exposure to smartphones and media multitasking were positively associated with impulsivity (ßsmartphone = 0.74; 99.9%CI = 0.42-1.07; ßMMT = 0.73; 99.9%CI = 0.35-1.12) and cognitive inflexibility (ßsmartphone = 0.32; 99.9%CI = -0.02-0.66; ßMMT = 0.39; 99.9%CI = 0.01-0.77) while being inversely associated with decision-making ability. Extensive smartphone/internet exposure combined with low computer/medium TV exposure was associated with higher impulsivity and cognitive inflexibility scores, especially in girls. DM exposure is adversely associated with cognitive functioning in children and adolescents. Children require protection against the likely adverse impact of digital environment.

Age-Specific Quantification of Overweight/Obesity Risk Factors From Infancy to Adolescence and Differences by Educational Level of Parents.

Objectives: To explore the age-dependent associations between 26 risk factors and BMI in early life, and differences by parental educational level. Methods: Data of 10,310 children (24,155 measurements) aged 2-16 years participating in a multi-centre European cohort from 2007 to 2014 were utilized. Trajectories of overweight/obesity risk factors and their age-specific associations with BMI were estimated using polynomial mixed-effects models. Results: Exposure to most unfavourable factors was higher in the low/medium compared to the high education group, e.g., for PC/TV time (12.6 vs. 10.6 h/week). Trajectories of various risk factors markedly changed at an age of 9-11 years. Having a family history of obesity, maternal BMI, pregnancy weight gain and birth weight were positively associated with BMI trajectories throughout childhood/adolescence in both education groups; associations of behavioural factors with BMI were small. Parental unemployment and migrant background were positively associated with BMI in the low/medium education group. Conclusion: Associations of risk factors with BMI trajectories did not essentially differ by parental education except for social vulnerabilities. The age period of 9-11 years may be a sensitive period for adopting unfavourable behaviours.

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.

Longitudinal association of childhood physical activity and physical fitness with physical activity in adolescence: insights from the IDEFICS/I.Family study.

BACKGROUND: This study aimed to examine associations of early childhood physical fitness and physical activity (PA) with PA during later childhood/early adolescence while accounting for gender differences. METHODS: We selected data of N = 4329 children from the IDEFICS/I. Family cohort (age 2.4-11.7 years) with data on baseline fitness and accelerometer measurements. At baseline, physical fitness tests were conducted including Flamingo balance, Backsaver sit and reach, Handgrip strength, Standing Long Jump, 40-m sprint and 20-m Shuttle run (to estimate cardio-respiratory fitness levels). PA was measured with Actigraph accelerometers over 3 days at baseline (ActiTrainer or GT1M) and 7 days at follow-up (GT3X). Evenson cutpoints were used to determine moderate-to-vigorous PA (MVPA) time, and children with ≥60mins/day of average MVPA were deemed as having met WHO guidelines at baseline and follow-up. Linear and logistic regressions were performed to examine longitudinal associations between meeting WHO guidelines, MVPA, and physical fitness tests at baseline with meeting WHO guidelines and MVPA at follow-up. Models were conducted on the entire sample, the sex-stratified sample, and stratified by sex and pubertal status at follow-up. RESULTS: Results showed that meeting WHO guidelines for MVPA at baseline was positively associated with MVPA (Standardized Beta (B) = 0.13, 95%CI:(5.6;11.1)) and meeting WHO guidelines at follow-up for the entire sample (OR = 2.1, 95%CI:(1.5; 3.14), and stratified by males (OR = 2.5, 95%CI:(1.5; 4.1)) and females (OR = 1.8, 95%CI:(1.0; 3.2)). This was also found for both male pre/early pubertal and pubertal groups but only in the female pre/early pubertal group, and not the female pubertal group (MVPA: B = .00, 95%CI:(- 6.1; 5.6), WHO: OR = 0.61, 95%CI:(0.23;1.6)). Models indicated that Standing Long jump, 40-m sprint, Shuttle run and Flamingo balance at baseline were associated with MVPA and meeting the guidelines at follow-up. CONCLUSIONS: Meeting WHO guidelines and certain fitness tests at baseline were strongly associated with MVPA and meeting WHO guidelines at follow-up, but this association varied with sex and pubertal status. Consequently, these findings underline the importance of ensuring sufficient physical activity in terms of quality and quantity for children at the earliest stages of life. TRIAL REGISTRATION: ISRCTN62310987.

Improving cardiorespiratory fitness protects against inflammation in children: the IDEFICS study.

BACKGROUND: Muscular and cardiorespiratory fitness (MF and CRF) have been related to inflammation. Thus, the aim of this study was to assess the relationship between fitness and high-sensitivity C-reactive protein (hs-CRP) in European children both in the cross-sectional and longitudinal analysis. METHODS: Three hundred and fifty-seven children (46.2% males) aged 2-9 years with hs-CRP measured, data from MF and CRF, diet quality, objectively measured physical activity (PA) and screen time at baseline and follow-up after 2 years were included. Body mass index z-score (zBMI), waist circumference (WC) and fat mass index (FMI) were assessed. MF and CRF were also dichotomized as follows: low-medium quartiles (Q1-Q3) and highest quartile (Q4). RESULTS: At follow-up, children with the highest CRF (Q4) showed a lower probability of having high hs-CRP. In the longitudinal analysis, children who improved their CRF over time showed a significantly lower probability (p < 0.05) of being in the highest hs-CRP category at follow-up, independently of the body composition index considered: odds ratio (OR) = 0.22 for zBMI, OR = 0.17 for WC, and OR = 0.21 for FMI. CONCLUSIONS: Improving CRF during childhood reduces the odds of an inflammatory profile, independently of body composition and lifestyle behaviours. These highlight the importance of enhancing fitness, especially CRF, to avoid an inflammatory state in children. IMPACT: Improvements in the cardiorespiratory profile during childhood could reverse an unfavourable inflammatory status. There is a longitudinal and inverse association between CRF and inflammation in children. This is the first longitudinal study assessing the relationship between fitness and inflammation during childhood that takes also into account the lifestyle behaviours. Results from the present study suggest a protective role of fitness already in childhood. Efforts to improve fitness in children should be aimed at as inflammation could trigger future cardiovascular disease.

Associations Between Psychosocial Well-Being, Stressful Life Events and Emotion-Driven Impulsiveness in European Adolescents.

Knowing the extent to which mental well-being and stressful life events during adolescence contribute to personality characteristics related to risk-taking behaviors, such as emotion-driven impulsiveness, is highly relevant for the development of health promotion measures. This study examined whether psychosocial well-being and different stressful life events are associated with emotion-driven impulsiveness. In total, 3,031 adolescents (52% girls; Mage = 13.6 years) were included from the I. Family Study, a cross-sectional examination on lifestyle-related behaviors conducted across eight European countries in 2013/14. Linear mixed-effects regression models showed that higher psychosocial well-being was associated with lower emotion-driven impulsiveness independent of socio-demographic, health-related, and parental variables. A higher number of stressful life events was associated with higher emotion-driven impulsiveness. Psychosocial well-being and stressful life events need to be further considered in the development and tailoring of health promotion strategies that aim to reduce emotion-driven impulsiveness.

Longitudinal association of inflammatory markers with markers of glycaemia and insulin resistance in European children.

PURPOSE: Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. METHODS: This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. RESULTS: Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (ß = -0.11, 95% CI = -0.15 to -0.07). CONCLUSIONS: IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.

25-Hydroxyvitamin D reference percentiles and the role of their determinants among European children and adolescents.

BACKGROUND/OBJECTIVES: To provide age- and sex-specific percentile curves of serum 25-hydroxyvitamin D (25(OH)D) by determinants from 3-<15 year-old European children, and to analyse how modifiable determinants influence 25(OH)D. SUBJECTS/METHODS: Serum samples were collected from children of eight European countries participating in the multicenter IDEFICS/I.Family cohort studies. Serum 25(OH)D concentrations were analysed in a central lab by a chemiluminescence assay and the values from 2171 children (N = 3606 measurements) were used to estimate percentile curves using the generalized additive model for location, scale and shape. The association of 25(OH)D with time spent outdoors was investigated considering sex, age, country, parental education, BMI z score, UV radiation, and dietary vitamin D in regressions models. RESULTS: The age- and sex-specific 5th and 95th percentiles of 25(OH)D ranged from 16.5 to 73.3 and 20.8 to 79.3 nmol/l in girls and boys, respectively. A total of 63% had deficient (<50 nmol/l), 33% insufficient (50-<75 nmol/l) and 3% sufficient (≥75 nmol/l) levels. 25(OH)D increased with increasing UV radiation, time spent outdoors, and vitamin D intake and slightly decreased with increasing BMI z score and age. The odds ratio (OR) for a non-deficient 25(OH)D status (reference category: deficient status) by one additional hour spent outdoors was 1.21, 95% CI [1.12-1.31], i.e., children who spent one more hour per day outdoors than other children had a 21% higher chance of a non-deficient than a deficient status. CONCLUSION: A majority of children suffer from deficient 25(OH)D. UV radiation, outdoor time, and dietary vitamin D are important determinants of 25(OH)D.

Ultra-processed foods consumption and diet quality of European children, adolescents and adults: Results from the I.Family study.

BACKGROUND AND AIMS: Food processing has been indicated as a factor capable of negatively affecting the global food system, including the profile of consumers' diets. The objectives of the present study were to provide a description of the consumption of ultra-processed foods (UPFs) in the large population of children, adolescents and adults from eight European countries participating to the I.Family study, and to investigate the association between UPFs intake and nutritional quality of the diet. METHODS AND RESULTS: Dietary intake was assessed using a 24-h dietary recall. The quality of the diet was evaluated by the Healthy Dietary Adherence Score (HDAS) using an FFQ. UPFs were classified according to the NOVA classification. Almost half of the daily energy intake of the 7073 participants came from UPFs, and this trend decreased progressively with age. UPFs contributed more than 50 % of the daily intake of total and saturated fat, carbohydrates and about 70 % of sugars intake in children and adolescents. No differences in UPFs consumption were found according to the educational and socio-economic status of the population. Energy intake increased across the quintiles of UPFs intake, while HDAS decreased. The frequency of consumption of fruit and vegetable, fish, and fibre rich foods was low in the fifth quintile of UPFs intake, both in adolescents and in adults. The consumption of foods rich in calories and low in nutritional content, operationally defined as "junk food", was significantly higher in the fifth quintile. CONCLUSIONS: In the population of the European I.Family study, UPFs contributed a large proportion of the daily energy intake, especially in children and adolescents. Higher consumption of UPFs was associated with a lower quality of the diet. REGISTRATION NUMBER FOR CLINICAL TRIALS: ISRCTN62310987.

Trajectories of objectively measured physical activity and childhood overweight: longitudinal analysis of the IDEFICS/I.Family cohort.

BACKGROUND: Since only few longitudinal studies with appropriate study designs investigated the relationship between objectively measured physical activity (PA) and overweight, the degree PA can prevent excess weight gain in children, remains unclear. Moreover, evidence is limited on how childhood overweight determines PA during childhood. Therefore, we analyzed longitudinal trajectories of objectively measured PA and their bi-directional association with weight trajectories of children at 2- and 6-year follow-ups. METHODS: Longitudinal data of three subsequent measurements from the IDEFICS/I.Family cohort study were used to analyze the bi-directional association between moderate-to-vigorous PA (MVPA) and weight status by means of multilevel regression models. Analyses comprised 3393 (2-year follow-up) and 1899 (6-year follow-up) children aged 2-15.9 years from eight European countries with valid accelerometer data and body mass index (BMI) measurements. For categorized analyses, children's weight status was categorized as normal weight or overweight (cutoff: 90th percentile of BMI) and children's PA as (in-) sufficiently active (cutoffs: 30, 45 and 60 min of MVPA per day). RESULTS: Children engaging in at least 60 min MVPA daily at baseline and follow-ups had a lower odds of becoming overweight (odds ratio [OR] at 2-year follow-up: 0.546, 95% CI: 0.378, 0.789 and 6-year follow-up: 0.393, 95% CI: 0.242, 0.638), compared to less active children. Similar associations were found for 45 min MVPA daily. On the other side, children who became overweight had the lowest odds to achieve 45 or 60 min MVPA daily (ORs: 0.459 to 0.634), compared to normal weight children. CONCLUSIONS: Bi-directional associations between MVPA and weight status were observed. In summary, at least 60 min MVPA are still recommended for the prevention of childhood overweight. To prevent excess weight gain, 45 min MVPA per day also showed preventive effects.

Impaired metabolic health over-time and high abdominal fat are prospectively associated with high-sensitivity C-reactive protein in children: The IDEFICS study.

BACKGROUND: Metabolic risk and inflammatory state have an early life onset and are associated with future diseases. OBJECTIVES: To assess the association between metabolic syndrome (MetS) and metabolic health with high-sensitive C-reactive protein (hsCRP), cross-sectionally and longitudinally, in children. METHODS: 2913 European children (2-10 years) from eight countries from the IDEFICS study were investigated. Data were collected at baseline and 2 years later (follow-up). A MetS z-score was computed with waist circumference (WC), insulin resistance index, blood pressure, high-density lipoprotein cholesterol and triglycerides. Metabolically unhealthy (MU) status was assessed. Multi-level linear and logistic regressions were performed. RESULTS: Among the MetS markers, WC was more consistently associated with hsCRP cross-sectional and prospectively. Baseline MetS score was significantly associated with greater risk of high hsCRP at follow-up and with prevalence and incidence of hsCRP. Those children who became MU overtime were significantly (P < .05) associated with future higher levels of hsCRP, independently of weight status at baseline. CONCLUSIONS: Transition over time to a MU state was associated with higher levels of hsCRP at follow-up, independent of weight status at baseline. Screening of metabolic factors and routine measurement of WC are needed to prevent inflammatory status and related chronic diseases in children.

Cross-Sectional and Longitudinal Associations Between Psychosocial Well-Being and Cardiometabolic Markers in European Children and Adolescents.

OBJECTIVE: Research examining aspects of positive mental health as potential predictors of cardiometabolic health in young populations is scarce. We investigated the associations between psychosocial well-being and waist circumference (WAIST), blood pressure (BP), the homeostasis model assessment for insulin resistance, triglycerides, and high-density lipoprotein cholesterol considering life-style factors as mediators. METHODS: Data of European children and adolescents participating in the baseline (2007/2008), first follow-up (FU1; 2009/2010) and second follow-up (FU2; 2013/2014) examinations of the IDEFICS/I.Family study were used (ncross-sectional = 6519; nlongitudinal = 1393). A psychosocial well-being score was calculated from 16 items on emotional well-being, self-esteem, and social relationships (0-48 points). Cardiometabolic markers were transformed to age- and sex-specific and, in case of BP, also height-specific z scores. Life-style factors included diet, physical activity, sleep, and electronic media use. Applying path analysis, we obtained unstandardized estimates of direct and indirect effects of well-being on cardiometabolic markers. RESULTS: Cross-sectionally, well-being score showed a negative direct and a negative indirect effect through life-style factors on WAIST z score (estimate per 4-point increase, -0.051 [p = .001] and -0.014 [p < .001], respectively). Longitudinally, positive changes in well-being score between baseline and FU1 and between FU1 and FU2, respectively, demonstrated negative indirect effects through life-style factorsFU2 on WAIST z scoreFU2. Both cross-sectionally and longitudinally, higher levels of well-being showed lowering indirect effects on homeostasis model assessment, BP, and triglyceride z scores and an increasing indirect effect on high-density lipoprotein cholesterol z score through both life-style factors and WAIST z score. CONCLUSIONS: These results supported our hypothesis that a healthier life-style may be one mechanism through which higher well-being is linked with lower abdominal obesity and fewer other cardiometabolic disorders in young populations. TRIAL REGISTRATION: Pan-European IDEFICS/I.Family children cohort, ISRCTN registry number: ISRCTN62310987 (http://www.isrctn.com/ISRCTN62310987).

The role of lifestyle and non-modifiable risk factors in the development of metabolic disturbances from childhood to adolescence.

BACKGROUND: The study aimed to identify the effects of lifestyle, C-reactive protein (CRP) and non-modifiable risk factors on metabolic disturbances in the transition from childhood to adolescence. METHODS: In 3889 children of the IDEFICS/I.Family cohort, latent transition analysis was applied to estimate probabilities of metabolic disturbances based on waist circumference, blood pressure, blood glucose, and lipids assessed at baseline and at 2- and 6-year follow-ups. Multivariate mixed-effects models were used to assess the age-dependent associations of lifestyle, non-modifiable risk factors and CRP, with the transformed probabilities of showing abdominal obesity, hypertension, dyslipidemia, or several metabolic disturbances (reference: being metabolically healthy). RESULTS: Higher maternal body mass index, familial hypertension as well as higher CRP z-score increased the risk for all four metabolic outcomes while low/medium parental education increased the risk of abdominal obesity and of showing several metabolic disturbances. Out of the lifestyle factors, the number of media in the bedroom, membership in a sports club, and well-being were associated with some of the outcomes. For instance, having at least one media in the bedroom increased the risk for showing several metabolic disturbances where the odds ratio (OR) markedly increased with age (1.30 [95% confidence interval 1.18; 1.43] at age 8; 1.18 [1.14; 1.23] for interaction with age; i.e., resulting in an OR of 1.30 × 1.18 = 1.53 at age 9 and so forth). Further, entering puberty at an early age was strongly associated with the risk of abdominal obesity (2.43 [1.60; 3.69] at age 8; 0.75 [0.69; 0.81] for interaction with age) and the risk of showing several metabolic disturbances (2.46 [1.53; 3.96] at age 8; 0.71 [0.65; 0.77] for interaction with age). CONCLUSIONS: Various factors influence the metabolic risk of children revealing the need for multifactorial interventions. Specifically, removing media from children's bedroom as well as membership in a sports club seem to be promising targets for prevention.

Associations between sleep duration and insulin resistance in European children and adolescents considering the mediating role of abdominal obesity.

BACKGROUND: Short sleep duration has been suggested to lead to insulin resistance both directly by altering glucose metabolism and indirectly through obesity. This study aims to investigate associations between nocturnal sleep duration and insulin resistance considering abdominal obesity as a mediator. METHODS: We analysed data of 3 900 children aged 2-15 years participating in the second (2009/10) and third (2013/14) examination wave of the European IDEFICS/I.Family study (hereafter referred to as baseline and follow-up). Information on nocturnal sleep duration was collected by questionnaires and age-standardised (SLEEP z-score). The homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose obtained from blood samples; waist circumference (WAIST) was measured with an inelastic tape. HOMA and WAIST were used as indicators for insulin resistance and abdominal obesity, respectively, and transformed to age- and sex-specific z-scores. Cross-sectional and longitudinal associations between SLEEP z-score and HOMA z-score were investigated based on a path model considering WAIST z-score as a mediator adjusting for relevant confounders. RESULTS: Cross-sectionally, baseline SLEEP z-score was negatively associated with baseline WAIST z-score (unstandardised effect estimate -0.120, 95% confidence interval [-0.167; -0.073]). We observed no direct effect of baseline SLEEP z-score on baseline HOMA z-score but a negative indirect effect through baseline WAIST z-score (-0.042 [-0.058; -0.025]). Longitudinally, there was no direct effect of baseline SLEEP z-score on HOMA z-score at follow-up but a negative indirect effect through both baseline WAIST z-score and WAIST z-score at follow-up (-0.028 [-0.040; -0.016]). CONCLUSIONS: Our results do not support the hypothesis of an association between short sleep duration and insulin resistance independent of abdominal obesity. However, longer sleep duration may exert short and long term beneficial effects on insulin resistance through its beneficial effects on abdominal obesity.

Associations of whole blood polyunsaturated fatty acids and insulin resistance among European children and adolescents.

This study aims to examine the association of whole blood n-3 and n-6 polyunsaturated fatty acids (PUFA) with insulin resistance (IR) in children. Whole blood fatty acids were measured in 705 children aged 2-9 years of the European IDEFICS/I.Family cohort using gas chromatography in units of weight percentage of all detected fatty acids (%wt/wt). IR was determined by the Homeostasis Model Assessment for IR (HOMA). Mixed effect models were used to assess the associations between selected baseline PUFA and HOMA z-scores at baseline and after 2- and 6-year follow-ups using models with basic and additional confounder adjustment as well as stratified by sex and weight status. In the basic model, α-linolenic (ß = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (ß = 1.17 SD/%wt/wt, p = 0.001) were positively associated with baseline HOMA z-score. In the stratified analyses, α-linolenic acid was positively associated with HOMA z-score in girls only (ß = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (ß = - 0.13 SD/%wt/wt, p = 0.0063). In the fully adjusted model, no statistically significant associations were seen.Conclusions: Our overall results do not indicate a protective role of higher blood n-3 PUFA or an adverse role of higher blood arachidonic acid proportion on the risk of IR. What is Known: •Intervention studies reported a beneficial effect of n-3 PUFA supplementation on insulin resistance compared with placebo while observational studies in cildren are inconclusive. •Studies have shown a positive association of n-6 arachidonic acid and insulin resistance indicating an adverse role of arachidonic acid. What is New: •Cross-sectional and longitudinal analyses based on circulating blood fatty acid concentrations in a large cohort of European children and adolescents. •Overall results do not support a protective role of n-3 PUFA or an adverse role of arachidonic acid in insulin resistance.