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Claudia Börnhorst,1 Tammo Reinders,1 Wolfgang Rathmann,2 Brenda Bongaerts,2 Ulrike Haug,1 Vanessa Didelez,1 Bianca Kollhorst1 1Leibniz Institute for Prevention Research and Epidemiology – BIPS, Department of Biometry and Data Management, Bremen, Germany; 2Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, GermanyCorrespondence: Bianca KollhorstLeibniz Institute for Prevention Research and Epidemiology – BIPS, Department of Biometry and Data Management, Achterstr. 30, Bremen, 28359, GermanyTel +49 421 21856980Email kollhorst@leibniz-bips.dePurpose: Investigating intended or unintended effects of sustained drug use is of high clinical relevance but remains methodologically challenging. This feasibility study aims to evaluate the usefulness of the parametric g-formula within a target trial for application to an extensive healthcare database in order to address various sources of time-related biases and time-dependent confounding.Patients and Methods: Based on the German Pharmacoepidemiological Research Database (GePaRD), we estimated the pancreatic cancer incidence comparing two hypothetical treatment strategies for type 2 diabetes mellitus (T2DM), i.e., (A) sustained metformin monotherapy vs (B) combination therapy with DPP-4 inhibitors after one year metformin monotherapy. We included 77,330 persons with T2DM who started metformin therapy at baseline between 2005 and 2011. Key aspects for avoiding time-related biases and time-dependent confounding were the emulation of a target trial over a 7-year follow-up period and application of the parametric g-formula.Results: Over the 7-year follow-up period, 652 out of the 77,330 study subjects had a diagnosis of pancreatic cancer. Assuming no unobserved confounding, we found evidence that the metformin/DPP-4i combination therapy increased the risk of pancreatic cancer compared to a sustained metformin monotherapy (risk ratio: 1.47; 95% bootstrap CI: 1.07– 1.94). The risk ratio decreased in sensitivity analyses addressing protopathic bias.Conclusion: While protopathic bias could not fully be ruled out, and computational challenges necessitated compromises in the analysis, the g-formula and target trial emulation proved useful: Self-inflicted biases were avoided, observed time-varying confounding was adjusted for, and the estimated risks have a clear causal interpretation.Keywords: target trial emulation, electronic health data, parametric g-formula, time-related bias, time-dependent confounding, type-2 diabetes mellitus

Dietary assessment is strongly affected by misreporting (both under- and over-reporting), which results in measurement error. Knowledge about misreporting is essential to correctly interpret potentially biased associations between diet and health outcomes. In young children, dietary data mainly rely on proxy respondents but little is known about determinants of misreporting here. The present analysis was conducted within the framework of the multi-centre IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study and is based on 6101 children aged 2–9 years with 24 h dietary recall (24-HDR) and complete covariate information. Adapted Goldberg cut-offs were applied to classify the 24-HDR as ‘over-report’, ‘plausible report’ or ‘under-report’. Backward elimination in the course of multi-level logistic regression analyses was conducted to identify factors significantly related to under- and over-reporting. Next to characteristics of the children and parents, social factors and parental concerns/perceptions concerning their child's weight status were considered. Further selective misreporting was addressed, investigating food group intakes commonly perceived as more or less socially desirable. Proportions of under-, plausible and over-reports were 8·0, 88·6 and 3·4 %, respectively. The risk of under-reporting increased with age (OR 1·19, 95 % CI 1·05, 1·83), BMI z-score of the child (OR 1·23, 95 % CI 1·10, 1·37) and household size (OR 1·12, 95 % CI 1·01, 1·25), and was higher in low/medium income groups (OR 1·45, 95 % CI 1·13, 1·86). Over-reporting was negatively associated with BMI z-scores of the child (OR 0·78, 95 % CI 0·69, 0·88) and higher in girls (OR 1·70, 95 % CI 1·27, 2·28). Further social desirability and parental concerns/perceptions seemed to influence the reporting behaviour. Future studies should involve these determinants of misreporting when investigating diet–disease relationships in children to correct for the differential reporting bias. [ABSTRACT FROM PUBLISHER]

Accurate food and nutrient intake assessment is essential for investigating diet–disease relationships. In the present study, food and nutrient intake assessment among European adolescents using 24 h recalls (mean of two recalls) and a FFQ (separately and the combination of both) were evaluated using concentration biomarkers. Biomarkers included were vitamin C, β-carotene, DHA+EPA, vitamin B12 (cobalamin and holo-transcobalamin) and folate (erythrocyte folate and plasma folate). For the evaluation of the food intake assessment 390 adolescents were included, while 697 were included for the nutrient intake assessment evaluation. Spearman rank and Pearson correlations, and validity coefficients, which are correlations between intake estimated and habitual true intake, were calculated. Correlations were higher between frequency of food consumption (from the FFQ) and concentration biomarkers than between mean food intake (from the recalls) and concentration biomarkers, especially for DHA+EPA (r 0·35 v. r 0·27). Most correlations were higher among girls than boys. For boys, the highest validity coefficients were found for frequency of fruit consumption (0·88) and for DHA+EPA biomarker (0·71). In girls, the highest validity coefficients were found for fruit consumption frequency (0·76), vegetable consumption frequency (0·74), mean fruit intake (0·90) and DHA+EPA biomarker (0·69). After exclusion of underreporters, correlations slightly improved. Correlations between usual food intakes, adjusted for food consumption frequency, and concentration biomarkers were higher than correlations between mean food intakes and concentration biomarkers. In conclusion, two non-consecutive 24 h recalls in combination with a FFQ seem to be appropriate to rank subjects according to their usual food intake. [ABSTRACT FROM PUBLISHER]

Objective: Measurement errors in dietary data lead to attenuated estimates of associations between dietary exposures and health outcomes. The present study aimed to compare and evaluate different approaches of handling implausible reports by exemplary analysis of the association between dietary intakes (total energy, soft drinks, fruits/vegetables) and overweight/obesity in children.Design: Cross-sectional multicentre study.Setting: Kindergartens/schools from eight European countries participating in the IDEFICS Study.Subjects: Children (n 5357) aged 2-9 years who provided one 24 h dietary recall and complete covariate information.Results: The 24 h recalls were classified into three reporting groups according to adapted Goldberg cut-offs: under-report, plausible report or over-report. In the basic logistic multilevel model (adjusted for age and sex, including study centre as random effect), the dietary exposures showed no significant association with overweight/obesity (energy intake: OR=0·996 (95 % CI 0·983, 1·010); soft drinks: OR = 0·999 (95 % CI 0·986, 1·013)) and revealed even a positive association for fruits/vegetables (OR = 1·009 (95 % CI 1·001, 1·018)). When adding the reporting group (dummy variables) and a propensity score for misreporting as adjustment terms, associations became significant for energy intake as well as soft drinks (energy: OR = 1·074 (95 % CI 1·053, 1·096); soft drinks: OR = 1·015 (95 % CI 1·000, 1·031)) and the association between fruits/vegetables and overweight/obesity pointed to the reverse direction compared with the basic model (OR = 0·993 (95 % CI 0·984, 1·002)).Conclusions: Associations between dietary exposures and health outcomes are strongly affected or even masked by measurement errors. In the present analysis consideration of the reporting group and inclusion of a propensity score for misreporting turned out to be useful tools to counteract attenuation of effect estimates. [ABSTRACT FROM AUTHOR]

Unlabelled: Sleep duration has been identified as risk factor for obesity already in children. Besides investigating the role of fat mass (FM), this study addressed the question whether endocrine mechanisms act as intermediates in the association between sleep duration and overweight/obesity. Within the framework of the IDEFICS study, the present research was conducted in 609 German resident children aged 2-9 years with information on fasting insulin, C-reactive protein and cortisol levels next to anthropometric measurements and parental questionnaires. Emphasising methodological aspects, an age-specific measure of sleep duration was derived to account for alteration in sleep duration during childhood/period of growth. Multivariate linear regression and quantile regression models confirmed an inverse relationship between sleep duration and measures of overweight/obesity. The estimate for the association of sleep duration and body mass index (BMI) was approximately halved after adjustment for FM, but remained significant. The strength of this association was also markedly attenuated when adjusting for insulin mainly for the upper BMI quantiles (Q80, β = -0.36 vs. β = -0.26; Q95, β = -0.87 vs. β = -0.47). Adjustment for cortisol and CrP did not yield this attenuation.Conclusion: The inverse relationship between sleep duration and BMI is mainly explained by the association between sleep duration and FM. Insulin may explain part of this association, in particular at the upper tail of the BMI distribution. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

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., (© 2023 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

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 KINDL R 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., (© 2023. The Author(s).)

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., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Börnhorst, Ahrens, De Henauw, Hunsberger, Molnár, Moreno, Russo, Schreuder, Sina, Tornaritis, Vandevijvere, Veidebaum, Vrijkotte, Wijnant and Wolters.)

Background: Living in single parent and blended families or as an only child-compared to living in two-parent biological families or with siblings, respectively-is associated with a higher body mass index (BMI) in cross-sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health., Objectives: This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS)., Methods: Cross-sectional data from 7804 children participating in the European multi-center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007-2010) were used. Family structure was assessed by a detailed interview. BMI z-score and the MetS were based on measured anthropometry, blood pressure, high-density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS., Results: Children from single-parent families had higher BMI z-scores in the cross-sectional (β = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two-parent families. Cross-sectionally, the number of siblings was associated with lower BMI z-scores (β = -0.07, 95% CI: -0.10 to -0.03) and lower MetS (β = -0.14, 95% CI: -0.26 to -0.01). Longitudinally, only children between baseline and follow-up had higher BMI z-scores at follow-up (β = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings., Conclusion: Obesity prevention measures should focus on single-parent households and families with an only child., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

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; M age  = 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., (© 2021. The Author(s).)

Objective: Chemerin is a novel inflammatory biomarker suggested to play a role in the development of metabolic disorders, providing new avenues for treatment and prevention. Little is known about the factors that predispose elevated chemerin concentrations. We therefore aimed to explore a range of lifestyle-associated, dietary, and metabolic factors as potential determinants of elevated chemerin concentrations in asymptomatic adults., Design: We used cross-sectional data from a random subsample of 2433 participants (1494 women and 939 men) aged 42-58 years of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort., Methods: Random forest regression (RFR) was applied to explore the relative importance of 32 variables as statistical predictors of elevated chemerin concentrations overall and by sex. Multivariable-adjusted linear regression was applied to evaluate associations between selected predictors and chemerin concentrations., Results: Results from RFR suggested BMI, waist circumference, C-reactive protein, fatty liver index, and estimated glomerular filtration rate as the strongest predictors of chemerin concentrations. Additional predictors included sleeping duration, alcohol, red and processed meat, fruits, sugar-sweetened beverages (SSB), vegetables, dairy, and refined grains. Collectively, these factors explained 32.9% variation of circulating chemerin. Multivariable-adjusted analyses revealed linear associations of elevated chemerin with metabolic parameters, obesity, longer sleep, higher intakes of red meat and SSB, and lower intakes of dairy., Conclusions: These findings come in support of the role of chemerin as a biomarker characterizing inflammatory and metabolic phenotypes in asymptomatic adults. Modifiable dietary and lifestyle-associated determinants of elevated chemerin concentrations require further evaluation in a prospective study setting.

The longitudinal study examined whether and how children's temperament traits in particular but also their age, sex as well as maternal education and age predict maternal socialization values. The sample was drawn from the IDEFICS study and included 567 mothers from Estonia whose children were 2-9 years old at Time 0 and 4-11 years old at Time 1. The findings showed that children's temperament at Time 0 predicted maternal socialization values at Time 1, but not vice versa. Mothers who perceived their child to be more imaginative at Time 0 considered self-maximization socialization values more important and social conformity-related values less important at Time 1. Child's conscientiousness and extraversion were linked positively to social conformity-related socialization values. Older mothers and those with higher level of education put more emphasis on self-maximization socialization values. Children's age and sex were not related to socialization values., (© 2021 The British Psychological Society.)

Purpose: Psychosocial stressors derived from socioeconomic disadvantages in adolescents can result in higher risk of metabolic syndrome (MetS). We aimed to examine whether socioeconomic disadvantages were associated with MetS independent of lifestyle and whether there was a dose-response relationship between the number of cumulated socioeconomic disadvantages and risk of MetS., Methods: This study included 1,037 European adolescents (aged 12.5-17.5 years). Sociodemographic variables and lifestyle were assessed by self-reported questionnaires. Disadvantaged groups included adolescents with low-educated parents, low family affluence, migrant origin, unemployed parents, and nontraditional families. MetS risk score was calculated as the sum of sex- and age-specific z-scores of waist circumference, blood pressure, lipids, and insulin resistance. Linear mixed-effects models adjusted for sex, age, pubertal status, and lifestyle were used to study the association between social disadvantages and MetS risk score., Results: Adolescents with low-educated mothers showed a higher MetS score (.54 [.09-.98]; β estimate and 99% confidence interval) compared to those with high-educated mothers. Adolescents who accumulated more than three disadvantages (.69 [.08-1.31]) or with missing information on disadvantages (.72 [.04-1.40]) had a higher MetS risk score compared to nonsocioeconomically disadvantaged groups. Stronger associations between socioeconomic disadvantages and MetS were found in male than in female adolescents., Conclusions: Adolescents with low-educated mothers or with more than three socioeconomic disadvantages had a higher MetS risk, independent of lifestyle, potentially due to higher psychosocial stress exposure. Policy makers should focus on improving low-educated familiesa and more disadvantaged families' knowledge on nutrition and physical activity to help them cope better with stress., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

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.

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).

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 (β = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (β = 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 (β = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (β = - 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.

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., Competing Interests: The authors declare no competing interests.

Many studies have shown that childhood circumstances can have long term consequences that persist until old age. To better understand the transmission of early life circumstances, this paper analyses the effects of health and financial situation during childhood on quality of life after retirement as well as the mediating role of later life health, educational level, and income in this association. Moreover, this study is the first to compare these pathways across European regions. The analyses are based on data of 13,092 retirees aged ≥ 60 and ≤ 85 years from the fifth wave of the Survey of Health, Aging, and Retirement in Europe (SHARE) with full information on childhood and later life measures of health, educational level, financial situation, and quality of life as well as relevant covariates. Five European regions are studied: Central-Western Europe (Austria, Germany), Central-Eastern Europe (Czech Republic, Estonia, Slovenia), Northern Europe (Denmark, Sweden), Southern Europe (Italy, Spain), and Western Europe (Belgium, France, The Netherlands). Path analysis is used to identify the direct and indirect effects of childhood measures on quality of life. We find retirees' quality of life to be associated with childhood finances and health in all five European regions. While both the direct and indirect effects of childhood health are rather moderate and homogeneous across regions, especially the direct effects of childhood finances on quality of life after retirement display a distinct North-South gradient being strongest in Southern Europe. Potential explanations for the regional variations are differences in the countries' welfare systems., Competing Interests: The authors have declared that no competing interests exist.