Children's stress-related reports and stress biomarkers interact in their association with metabolic syndrome risk

The purpose was to examine the cross-sectional associations of stress-related reports and stress biomarkers with metabolic syndrome (MetS) risk in children while also testing the interaction between stress biomarkers and stress reports. In 353 children (5-10years old, 7.9% overweight/obese), MetS risk was measured by blood pressure, waist circumference, glucose homeostasis, triglycerides, and high-density cholesterol. Stress was measured by stress-related reports (events, emotions, and internalizing/externalizing problems) and two biomarkers: salivary cortisol (total-day and morning output) and heart rate variability (percentage of consecutive normal RR intervals differing more than 50ms and low-to-high-frequency ratio). Cross-sectional regression analyses with z scored total MetS risk as outcome were adjusted for age, sex, and socio-economic status. Only internalizing problems were directly related to a higher MetS risk score (=0.236). Cortisol and heart rate variability were significant moderators: High cortisol morning output resulted in a positive (unfavourable) report-MetS relationship (=0.259-0.552), whereas low percentage of consecutive normal RR intervals differing more than 50ms resulted in a negative (favourable) report-MetS relationship (=-0.298) and low low-to-high-frequency ratio in a positive (unfavourable) report-MetS relationship (=0.478). In conclusion, stress can sometimes be a disadvantageous factor in metabolic health of otherwise healthy children. The cortisol biomarker seems relevant because metabolic risk was highest when stress-related reports were accompanied by high morning cortisol output

Impact of physical activity, sedentary behaviour and muscle strength on bone stiffness in 2-10-year-old children-cross-sectional results from the IDEFICS study

Background: Physical activity (PA), weight-bearing exercises (WBE) and muscle strength contribute to skeletal development, while sedentary behaviour (SB) adversely affects bone health. Previous studies examined the isolated effect of PA, SB or muscle strength on bone health, which was usually assessed by x-ray methods, in children. Little is known about the combined effects of these factors on bone stiffness (SI) assessed by quantitative ultrasound. We investigated the joint association of PA, SB and muscle strength on SI in children. Methods: In 1512 preschool (2- < 6 years) and 2953 school children (6-10 years), data on calcaneal SI as well as on accelerometer-based sedentary time (SED), light (LPA), moderate (MPA) and vigorous PA (VPA) were available. Parents reported sports (WBE versus no WBE), leisure time PA and screen time of their children. Jumping distance and handgrip strength served as indicators for muscle strength. The association of PA, SB and muscle strength with SI was estimated by multivariate linear regression, stratified by age group. Models were adjusted for age, sex, country, fat-free mass, daylight duration, consumption of dairy products and PA, or respectively SB. Results: Mean SI was similar in preschool (79.5 +/- 15.0) and school children (81.3 +/- 12.1). In both age groups, an additional 10 min/day in MPA or VPA increased the SI on average by 1 or 2 %, respectively (p = .05). The negative association of SED with SI decreased after controlling for MVPA. LPA was not associated with SI. Furthermore, participation in WBE led to a 3 and 2 % higher SI in preschool (p = 0.003) and school children (p < .001), respectively. Although muscle strength significantly contributed to SI, it did not affect the associations of PA with SI. In contrast to objectively assessed PA, reported leisure time PA and screen time showed no remarkable association with SI. Conclusion: This study suggests that already an additional 10 min/day of MPA or VPA or the participation in WBE may result in a relevant increase in SI in children, taking muscle strength and SB into account. Our results support the importance of assessing accelerometer-based PA in large-scale studies. This may be important when deriving dose-response relationships between PA and bone health in children

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

Celiac Disease and Anorexia Nervosa: A Nationwide Study

BACKGROUND AND OBJECTIVE: Previous research suggests an association of celiac disease (CD) with anorexia nervosa (AN), but data are mostly limited to case reports. We aimed to determine whether CD is associated with the diagnosis of AN. METHODS: Register-based cohort and case-control study including women with CD (n = 17 959) and sex- and age-matched population-based controls (n = 89 379). CD (villous atrophy) was identified through the histopathology records of Sweden's 28 pathology departments. Inpatient and hospital-based outpatient records were used to identify AN. Hazard ratios for incident AN diagnosis were estimated by using stratified Cox regression with CD diagnosis as a time-dependent exposure variable. In the secondary analyses, we used conditional logistic regression to estimate odds ratios for being diagnosed with AN before CD. RESULTS: Median age of CD diagnosis was 28 years. During 1 174 401 person-years of follow-up, 54 patients with CD were diagnosed with AN (27/100 000 person-years) compared with 180 matched controls (18/100 000 person-years). The hazard ratio for later AN was 1.46 (95% confidence interval [CI], 1.08-1.98) and 1.31 beyond the first year after CD diagnosis (95% CI, 0.95-1.81). A previous AN diagnosis was also associated with CD (odds ratio, 2.18; 95% CI, 1.45-3.29). Estimates remained largely unchanged when adjusted for socioeconomic characteristics and type 1 diabetes. CONCLUSIONS: The bidirectional association between AN diagnosis and CD warrants attention in the initial assessment and follow-up of these conditions because underdiagnosis and misdiagnosis of these disorders likely cause protracted and unnecessary morbidity

Urinary mineral concentrations in European pre-adolescent children and their association with calcaneal bone quantitative ultrasound measurements

This study investigates differences and associations between urinary mineral concentrations and calcaneal bone measures assessed by quantitative ultrasonography (QUS) in 4322 children (3.1–11.9 years, 50.6% boys) from seven European countries. Urinary mineral concentrations and calcaneal QUS parameters differed significantly across countries. Clustering revealed a lower stiffness index (SI) in children with low and medium urinary mineral concentrations, and a higher SI in children with high urinary mineral concentrations. Urinary sodium (uNa) was positively correlated with urinary calcium (uCa), and was positively associated with broadband ultrasound attenuation and SI after adjustment for age, sex and fat-free mass. Urinary potassium (uK) was negatively correlated with uCa but positively associated with speed of sound after adjustment. No association was found between uCa and QUS parameters after adjustment, but when additionally adjusting for uNa, uCa was negatively associated with SI. Our findings suggest that urinary mineral concentrations are associated with calcaneal QUS parameters and may therefore implicate bone properties. These findings should be confirmed in longitudinal studies that include the food intake and repeated measurement of urinary mineral concentrations to better estimate usual intake and minimize bias

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

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