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.

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.

Sleep duration and blood pressure in children: Analysis of the pan-European IDEFICS cohort.

The present study aims to examine the cross-sectional and longitudinal association between self-reported nocturnal sleep duration, blood pressure, and hypertension in European children, aged 2-9.9 years, participating in the IDEFICS project. Blood pressure (BP) and the main anthropometric indices were measured according to standardized procedures. Childhood elevated BP and hypertension were defined according to the European Society of Hypertension Guidelines for children and adolescents. Parents reported lifestyle and socio-demographic data. Nocturnal sleep duration was assessed as part of a parental 24-h recall and categorized as follows: (a) ≤9 hours/night; (b) >9 hours to ≤10 hours/night; (c) >10 hours to ≤11 hours/night; and (d) >11 hours/night. A complete set of variables included in the present analysis was provided by 7974 participants (boys/girls = 4049/3925) at the baseline survey (T0). Of them, 5656 were re-examined 2 years later at follow-up (T1). Children reporting shorter sleep duration at T0 had significantly higher BP values (P for trend < 0.001) compared to those who slept more. Prospective analyses showed that shorter sleep duration at baseline predicted, over the 2-year follow-up, higher increases in systolic blood pressure and diastolic blood pressure, after adjustment for age, sex, country of origin, BMI z-score, parental education, physical activity, screen time, and T0 value of the examined outcome variables (P for trend < 0.001). Our findings reveal that shorter sleep duration is associated with higher BP in childhood, suggesting that sleep may be a potential risk factor for hypertension later in life.

Pre-obese children's dysbiotic gut microbiome and unhealthy diets may predict the development of obesity.

It is widely accepted that the intestinal microbiome is connected to obesity, as key mediator of the diet impact on the host metabolic and immunological status. To investigate whether the individual gut microbiome has a potential in predicting the onset and progression of diseases, here we characterized the faecal microbiota of 70 children in a two-time point prospective study, within a four-year window. All children had normal weight at the beginning of this study, but 36 of them gained excessive weight at the subsequent check-up. Microbiome data were analysed together with the hosts' diet information, physical activity, and inflammatory parameters. We find that the gut microbiota structures were stratified into a discrete number of groups, characterized by different biodiversity that correlates with inflammatory markers and dietary habits, regardless of age, gender, and body weight. Collectively, our data underscore the importance of the microbiome-host-diet configuration as a possible predictor of obesity.

Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study.

PURPOSE: This prospective study explores high sensitivity C-reactive protein (hs-CRP) levels in relation to dietary patterns at two time points in European children. METHODS: Out of the baseline sample of the IDEFICS study (n = 16,228), 4020 children, aged 2-9 years at baseline, with available hs-CRP levels and valid data from a food frequency questionnaire (FFQ) at baseline (T0) and 2 years later (T1) were included. K-means clustering algorithm based on the similarities between relative food consumption frequencies of the FFQ was applied. hs-CRP was dichotomized according to sex-specific cutoff points. Multilevel logistic regression was performed to assess the relationship between dietary patterns and hs-CRP adjusting for covariates. RESULTS: Three consistent dietary patterns were found at T0 and T1: 'animal protein and refined carbohydrate', 'sweet and processed' and 'healthy'. Children allocated to the 'protein' and 'sweet and processed' clusters at both time points had significantly higher odds of being in the highest category of hs-CRP (OR 1.47; 95% CI 1.03-2.09 for 'animal protein and refined carbohydrate' and OR 1.44; 95% CI 1.08-1.92 for 'sweet and processed') compared to the 'healthy' cluster. The odds remained significantly higher for the 'sweet and processed' pattern (OR 1.39; 95% CI 1.05-1.84) when covariates were included. CONCLUSIONS: A dietary pattern characterized by frequent consumption of sugar and processed products and infrequent consumption of vegetables and fruits over time was independently related with inflammation in European children. Efforts to improve the quality of the diet in childhood may prevent future diseases related with chronic inflammation.

Association of desaturase activity and C-reactive protein in European children.

BACKGROUND: Desaturase enzymes influence the fatty acid (FA) composition of body tissues and their activity affects the conversion rate of saturated to monounsaturated FA and of polyunsaturated FA (PUFA) to long-chain PUFA. Desaturase activity has further been shown to be associated with inflammation. We investigate the association between delta-9 (D9D), delta-6 (D6D) and delta-5 desaturase (D5D) activity and high-sensitive C-reactive protein (CRP) in young children. METHODS: In the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort study children were examined at baseline (T0) and after 2 y (T1). D9D, D6D, and D5D activities were estimated from T0 product-precursor FA ratios. CRP was measured at T0 and T1. In a subsample of 1,943 children with available information on FA, CRP, and covariates, the cross-sectional and longitudinal associations of desaturase activity and CRP were analyzed. RESULTS: Cross-sectionally, a D9D increase of 0.01 units was associated with a 11% higher risk of having a serum CRP ≥ Percentile 75 (P75) (OR, 99% CI: 1.11 (1.01; 1.22)) whereas D6D and D5D were not associated with CRP. No significant associations were observed between baseline desaturase activity and CRP 2 y later. CONCLUSION: Cross-sectionally, our results indicate a positive association of D9D and CRP independent of weight status. High D9D activity may increase the risk of subclinical inflammation which is associated with metabolic disorders. As D9D expression increases with higher intake of saturated FA and carbohydrates, dietary changes may influence D9D activity and thus CRP. However, it remains to be investigated whether there is a causal relationship between D9D activity and CRP.

Longitudinal associations of lifestyle factors and weight status with insulin resistance (HOMA-IR) in preadolescent children: the large prospective cohort study IDEFICS.

BACKGROUND: This study investigates prospective associations of anthropometrical and lifestyle indices with insulin resistance (IR) in European children from the IDEFICS cohort. Insulin resistance (IR) is a growing concern in childhood obesity and a central aspect of the metabolic syndrome (MS). It most likely represents the link between obesity and type 2 diabetes. METHODS: This longitudinal study included 3348 preadolescent children aged 3 to 10.9 years from 8 European countries who were observed from 2007/2008 to 2009/2010. The main outcome measure in the present analysis is HOMA-IR (homeostasis model assessment as a common proxy indicator to quantify IR) at follow-up and in its longitudinal development. Anthropometrical measures and lifestyle indices, including objectively determined physical activity, were considered, among others factors, as determinants of IR. Prospective associations between IR at follow-up and anthropometrical and lifestyle indices were estimated by logistic regression models. RESULTS: Country-specific prevalence rates of IR in the IDEFICS cohort of European children showed a positive trend with weight category. Prospective multivariate analyses showed the strongest positive associations of IR with BMI z-score (OR = 2.6 for unit change from the mean, 95 % CI 2.1-3.1) and z-score of waist circumference (OR = 2.2 for unit change from the mean, 95 % CI 1.9-2.6), which were analysed in separate models, but also for sex (OR = 2.2 for girls vs. boys, 95 % CI 1.5-3.1 up to OR 2.5, 95 % CI 1.8-3.6 depending on the model), audio-visual media time (OR = 1.2 for an additional hour per day, 95 % CI 1.0-1.4 in both models) and an inverse association of objectively determined physical activity (OR = 0.5 for 3(rd) compared to 1(st) quartile, 95 % CI 0.3-0.9 in both models). A longitudinal reduction of HOMA-IR was accompanied with a parallel decline in BMI. CONCLUSIONS: This study is, to our knowledge, the first prospective study on IR in a preadolescent children's population. It supports the common hypothesis that overweight and obesity are the main determinants of IR. Our data also indicate that physical inactivity and a sedentary lifestyle are likewise associated with the development of IR, independent of weight status. The promotion of physical activity should thus be considered as an equal option to dietary intervention for the treatment of IR in the paediatric practice.

Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children.

CONTEXT: Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia. OBJECTIVE: To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally. DESIGN: The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1). SETTING AND PARTICIPANTS: Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses. METHODS: Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes. RESULTS: In the cross-sectional analysis, D9D and D6D were positively associated with BMI and TG z-scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG ≥ 75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score. CONCLUSION: Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk.

High-sensitivity C-reactive protein is a predictive factor of adiposity in children: results of the identification and prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) study.

BACKGROUND: Whereas cross-sectional studies have shown that obesity is associated with increased C-reactive protein (CRP) levels in children, little is known about the impact of low-grade inflammation on body mass changes during growth. METHODS AND RESULTS: We assessed cross-sectionally and longitudinally the association of high-sensitivity (hs)-CRP levels with overweight/obesity and related cardiometabolic risk factors in the Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and InfantS (IDEFICS) cohort. 16 224 children from 8 European countries (2 to 9 years) were recruited during the baseline survey (T0). After the exclusion of 7187 children because of missing hs-CRP measurements and 2421 because of drug use during the previous week, the analysis was performed on 6616 children (Boys=3347; Girls=3269; age=6.3 ± 1.7 years). Of them, 4110 were reexamined 2 years later (T1). Anthropometric variables, blood pressure, hs-CRP, blood lipids, glucose and insulin were measured. The population at T0 was divided into 3 categories, according to the baseline hs-CRP levels. Higher hs-CRP levels were associated with significantly higher prevalence of overweight/obesity, body mass index (BMI) z-score and central adiposity indices (P values all <0.0001), and with higher blood pressure and lower HDL-cholesterol levels. Over the 2-year follow-up, higher baseline hs-CRP levels were associated with a significant increase in BMI z-score (P<0.001) and significantly higher risk of incident overweight/obesity. CONCLUSIONS: Higher hs-CRP levels are associated to higher body mass and overweight/obesity risk in a large population of European children. Children with higher baseline levels of hs-CRP had a greater increase in BMI z-score and central adiposity over time and were at higher risk of developing overweight/obesity during growth.

Blood cells as a source of transcriptional biomarkers of childhood obesity and its related metabolic alterations: results of the IDEFICS study.

BACKGROUND: IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants Project) is a European multicenter study on childhood obesity. One of its goals is to define early biomarkers of risk associated with obesity and its comorbid conditions. OBJECTIVE: We considered blood cells as a new potential source of transcriptional biomarkers for these metabolic disorders and examined whether blood cell mRNA levels of some selected genes (LEPR, INSR, CPT1A, SLC27A2, UCP2, FASN, and PPARα) were altered in overweight children and whether their expression levels could be defined as markers of the insulin-resistant or dyslipidemic state associated with overweight. DESIGN: Blood samples were obtained from 306 normal-weight and overweight children, aged 2-9 yr, from eight different European countries. Whole-blood mRNA levels were assessed by quantitative RT-PCR. RESULTS: LEPR, INSR, and CPT1A mRNA levels were higher in overweight compared with normal-weight children (the two latter only in males), whereas SLC27A2 mRNA levels were lower in overweight children. Significant associations were also found between expression levels of LEPR, INSR, CPT1A, SLC27A2, FASN, PPARα, and different parameters, including body mass index, homeostasis model assessment index, and plasma triglycerides and cholesterol levels. These associations showed that high expression levels of CPT1A, SLC27A2, INSR, FASN, or PPARα may be indicative of a lower risk for the insulin-resistant or dyslipidemic state associated with obesity, whereas low LEPR mRNA levels appear as a marker of high low-density lipoprotein cholesterol, independently of body mass index. CONCLUSIONS: These findings point toward the possibility of using the expression levels of these genes in blood cells as markers of metabolic status and can potentially provide an early warning of a future disorder.

ISO 18812--a worldwide standard for the online-connection of analytical instruments to laboratory information systems.

In the past there were many attempts to standardize the interface from analytical instruments to laboratory-information-systems. Most of these attempts were national. The international standardisation bodies CEN and ISO have now developed an international standard that is presented here.