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 PPAR alpha) 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, PPAR alpha, 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 PPAR alpha 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

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 3rd compared to 1st 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

Blood lipids among young children in Europe : results from the European IDEFICS study

BACKGROUND: Measurement of cholesterol and triglyceride (TG) fractions in blood has become standard practice in the early detection of atherosclerotic disease pathways. Considerable attention is given nowadays to the presence of these risk factors in children and to start preventive campaigns early in life. In this context, it is imperative to have valid comparative frameworks for interpretation of lipid levels. The aim of this study is to present sex-and age-specific reference values on blood lipid levels in European children aged 2.0-10.9 years. METHODS: Fasting blood was obtained via either venipuncture or capillary sampling. In 13 579 European non-obese children (50.3% boys), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TG and TC/HDL-C ratio levels were measured with a point-of-care analyser (Cholestech). Sex- and age-specific reference values were computed with the GAMLSS method with the statistical software R. RESULTS: Reference curves and 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile values are presented. HDL-C showed a positive trend with age, from 2 years onwards, but was relatively stable above the age of 7. For LDL-C and TC, linear but small age-related trends were seen. The TC/HDL-C values showed a gradual negative trend from the age of 2 up to 6 and were relatively stable afterwards. For TG, no age trend was found (P = 0.285). Boys had higher mean HDL-C values than girls (1.414 vs 1.368 mmol l(-1)), and lower TC, LDL-C, TC/HDL-C and TG values (3.981 vs 4.087 mmol l(-1); 2.297 vs 2.435 mmol l(-1); 2.84 vs 3.01mmol l(-1); and 0.509 vs 0.542 mmol l(-1), respectively). CONCLUSIONS: These new and recent references could serve as a European orientation of blood lipid values in children in the context of standard medical practice and for the purpose of public health screening

A new internal quality control chart based on biological variation

Serteser, Mustafa/0000-0001-7868-7613; Coskun, Abdurrahman/0000-0002-1273-0604WOS: 000253210900003The instruments and analytical methods currently used in clinical laboratories today have better precision and stability than those used in the past. With the development of chemical and immunological methods and instrumentation technology, test precision has increased. However, the application of the Westgard multirule procedure to control sera in the Levey-Jennings chart may not be useful or cost-effective. We devised a new test-specific decision limit for accepting or rejecting runs based on the data of within-subject biological variation and prepared a control chart. We then applied these new limits and control chart to a group of tests performed in our laboratory. With the exception of the tests for albumin, total protein, and calcium, for which desirable performance standards could not be attained with the current technology and methodology, the application of these control limits was cost-effective and convenient. It is estimated that the value of healthy within-subject biological variations is constant, irrespective of the methodology, the area in which the study has been performed, and the number of subjects included in the study. We believe that control limits based on biological variation are reliable and cost-effective, and may be useful in modern and accredited laboratories

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) &lt;= 9 hours/night; (b) &gt;9 hours to &lt;= 10 hours/night; (c) &gt;10 hours to &lt;= 11 hours/night; and (d) &gt;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 &lt; 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 &lt; 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

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 PPAR alpha) 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, PPAR alpha, 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 PPAR alpha 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

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), andD5D(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