Cross-sectional associations between physical fitness and biomarkers of inflammation in children-The PANIC study.

BACKGROUND: Systemic low-grade inflammation has been proposed as an underlying pathophysiological mechanism for cardiometabolic diseases. We investigated the associations of physical fitness with a systemic low-grade inflammatory state in a population sample of children. METHODS: Altogether 391 children aged 6-9 years were examined. Cardiorespiratory fitness (maximal power output, Wmax ) was assessed by a maximal cycle ergometer test and neuromuscular fitness by hand grip strength, sit-up, standing long jump, 50-meter shuttle run, static balance, sit-and-reach, and box and block tests. Body fat percentage (BF%) and lean mass (LM) were assessed by dual-energy X-ray absorptiometry (DXA). High sensitivity C-reactive protein (hs-CRP), leptin, leptin receptor, high molecular weight adiponectin (HMW-adiponectin), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and glycoprotein acetyls (GlycA) were assessed from fasting blood samples. The modified inflammatory score (IS) was calculated using the population-specific z-scores and formula (z hs-CRP + z leptin + z IL-6 + z TNF-α + z GlycA)-z leptin receptor-z HMW-adiponectin. The data were analyzed using linear regression analyses. RESULTS: Higher Wmax /kg of body mass (ß = -0.416, 95% CI = -0.514 to -0.318), higher number of completed sit-ups (ß = -0.147, 95% CI = -0.244 to -0.049), a longer distance jumped in the standing long jump test (ß = -0.270, 95% CI = -0.371 to -0.169), and a shorter time in the 50-meter shuttle run test (ß = 0.123, 95% CI = 0.022 to 0.223) were associated with lower IS. None of these associations remained statistically significant after adjustment for BF%. CONCLUSIONS: Higher physical fitness is associated with a more favorable inflammatory biomarker profile in children. However, the associations were explained by BF%.

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.

Peak oxygen uptake cut-points to identify children at increased cardiometabolic risk - The PANIC Study.

We aimed to develop cut-points for directly measured peak oxygen uptake ( V ˙ O 2 peak ) to identify boys and girls at increased cardiometabolic risk using different scaling methods to control for body size and composition. Altogether 352 children (186 boys, 166 girls) aged 9-11 years were included in the analyses. We measured V̇O2peak directly during a maximal cycle ergometer exercise test and lean body mass (LM) by bioelectrical impedance. We computed a sex- and age-specific cardiometabolic risk score (CRS) by summing important cardiometabolic risk factors and defined increased cardiometabolic risk as >1 standard deviation above the mean of CRS. Receiver operating characteristics curves were used to detect V̇O2peak cut-points for increased cardiometabolic risk. Boys with V̇O2peak <45.8 mL kg body mass (BM)-1  min-1 (95% confidence interval [CI] = 45.1 to 54.6, area under the curve [AUC] = 0.86, P < 0.001) and <63.2 mL kg LM-1  min-1 (95% CI =52.4 to 67.5, AUC = 0.65, P = 0.006) had an increased CRS. Girls with V̇O2peak <44.1 mL kg BM-1  min-1 (95% CI = 44.0 to 58.6, AUC = 0.67, P = 0.013) had an increased CRS. V̇O2peak scaled by BM-0.49 and LM-0.77 derived from log-linear allometric modeling poorly predicted increased cardiometabolic risk in boys and girls. In conclusion, directly measured V ˙ O 2 peak <45.8 mL kg BM-1  min-1 among boys and <44.1 mL kg BM-1  min-1 among girls were cut-points to identify those at increased cardiometabolic risk. Appropriately controlling for body size and composition reduced the ability of cardiorespiratory fitness to identify children at increased cardiometabolic risk.

Associations of physical activity, sedentary time, and cardiorespiratory fitness with heart rate variability in 6- to 9-year-old children: the PANIC study.

PURPOSE: To study the associations of physical activity (PA), sedentary time (ST), and cardiorespiratory fitness (CRF) with heart rate variability (HRV) in children. METHODS: The participants were a population sample of 377 children aged 6-9 years (49% boys). ST, light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA), and PA energy expenditure (PAEE) were assessed using a combined heart rate and movement sensor, maximal power output per kilograms of lean body mass as a measure of CRF by maximal cycle ergometer exercise test, and HRV variables (SDNN, RMSSD, LF, and HF) using 5 min resting electrocardiography. Data were analysed by linear regression adjusted for years from peak height velocity. RESULTS: In boys, ST was inversely associated (ß = - 0.185 to - 0.146, p ≤ 0.049) and MVPA, VPA, PAEE, and CRF were directly associated (ß = 0.147 to 0.320, p ≤ 0.048) with HRV variables. CRF was directly associated with all HRV variables and PAEE was directly associated with RMSSD after mutual adjustment for ST, PAEE, and CRF (ß = 0.169 to 0.270, p ≤ 0.046). In girls, ST was inversely associated (ß = - 0.382 to - 0.294, p < 0.001) and LPA, MPA, VPA, MVPA, and PAEE were directly associated with HRV variables (ß = 0.144 to 0.348, p ≤ 0.049). After mutual adjustment for ST, PAEE, and CRF, only the inverse associations of ST with HRV variables remained statistically significant. CONCLUSIONS: Higher ST and lower PA and CRF were associated with poorer cardiac autonomic nervous system function in children. Lower CRF in boys and higher ST in girls were the strongest correlates of poorer cardiac autonomic function.

Associations of Cardiorespiratory Fitness and Adiposity With Arterial Stiffness and Arterial Dilatation Capacity in Response to a Bout of Exercise in Children.

Purpose: To investigate the associations of directly measured peak oxygen uptake ( V˙O2peak ) and body fat percentage (BF%) with arterial stiffness and arterial dilatation capacity in children. Methods: Findings are based on 329 children (177 boys and 152 girls) aged 8-11 years. V˙O2peak was assessed by a maximal cardiopulmonary exercise test on a cycle ergometer and scaled by lean body mass (LM). BF% and LM were measured by bioelectrical impedance. Stiffness index (measure of arterial stiffness) and change in reflection index (ΔRI, measure of arterial dilatation capacity) were assessed by pulse contour analysis. Data were analyzed by linear regression models. Results:V˙O2peak/LM was positively associated with ΔRI in boys adjusted for age and BF% (ß = 0.169, P = .03). Further adjustments for systolic blood pressure, heart rate, and the study group had no effect on this association, but additional adjustment for clinical puberty attenuated it (ß = 0.171, P = .07). BF% was inversely related to ΔRI in boys adjusted for age and V˙O2peak/LM (ß = -0.171, P = .03). V˙O2peak or BF% was not associated with ΔRI in girls or with stiffness index in either boys or girls. Conclusion: Increasing cardiorespiratory fitness and decreasing adiposity may improve arterial health in childhood, especially among boys.

Adiposity, physical activity and neuromuscular performance in children.

We investigated the associations of body fat percentage (BF%), objectively assessed moderate-to-vigorous physical activity (MVPA) and different types of physical activity assessed by a questionnaire with neuromuscular performance. The participants were 404 children aged 6-8 years. BF% was assessed using dual-energy x-ray absorptiometry and physical activity by combined heart rate and movement sensing and a questionnaire. The results of 50-m shuttle run, 15-m sprint run, hand grip strength, standing long jump, sit-up, modified flamingo balance, box-and-block and sit-and-reach tests were used as measures of neuromuscular performance. Children who had a combination of higher BF% and lower levels of physical activity had the poorest performance in 50-m shuttle run, 15-m sprint run and standing long jump tests. Higher BF% was associated with slower 50-m shuttle run and 15-m sprint times, shorter distance jumped in standing long jump test, fewer sit-ups, more errors in balance test and less cubes moved in box-and-block test. Higher levels of physical activity and particularly MVPA assessed objectively by combined accelerometer and heart rate monitor were related to shorter 50-m shuttle run and 15-m sprint times. In conclusion, higher BF% and lower levels of physical activity and particularly the combination of these two factors were associated with worse neuromuscular performance.

Cardiorespiratory fitness, respiratory function and hemodynamic responses to maximal cycle ergometer exercise test in girls and boys aged 9-11 years: the PANIC Study.

PURPOSE: We aimed to provide comprehensive data on and reference values for cardiorespiratory fitness, respiratory function and hemodynamic responses during and after maximal cycle ergometer test in children. METHODS: The participants were a population sample of 140 children (69 girls) aged 9-11 years. Heart rate (HR) and systolic blood pressure (SBP) were measured from pre-exercise rest to the end of recovery. Respiratory gases were measured directly by the breath-by-breath method. Peak workload, HR changes, peak oxygen uptake (VO2), peak oxygen pulse (O2 pulse), peak respiratory exchange ratio (RER) and the lowest ratio of ventilation and carbon dioxide output (VE/VCO2) during the exercise test in girls and boys were presented according to their distributions in 5 categories. RESULTS: HR decreased more during 4-min recovery in boys than in girls (76 vs. 67 beats/min, p < 0.001), whereas SBP decrease was similar in boys and girls (30 vs. 22 mmHg, p = 0.66). Boys had a higher peak VO2 per weight [51.9 vs. 47.6 ml/kg/min, p < 0.001] and per lean mass [67.3 vs. 63.0 ml/kg/min, p < 0.001] than girls. Peak O2 pulse per lean mass was higher in boys than in girls (0.34 vs. 0.31 ml/kg/beat, p < 0.001). There was no difference in the lowest VE/VCO2 during the test between boys and girls (28 vs. 29, p = 0.18). CONCLUSIONS: The indicators of cardiorespiratory fitness were better in boys than in girls. These data enable the evaluation of cardiorespiratory function during and after maximal exercise test and the detection of children with abnormal values.

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults.

AIMS/HYPOTHESIS: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men. METHODS: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men. RESULTS: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score. CONCLUSIONS: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Physical activity and sedentary behaviour in relation to cardiometabolic risk in children: cross-sectional findings from the Physical Activity and Nutrition in Children (PANIC) Study.

BACKGROUND: Lower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children. METHODS: The subjects were a population sample of 468 children 6-8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models. RESULTS: Total PA was inversely associated with the cardiometabolic risk score (ß = -0.135, p = 0.004), body fat percentage (ß = -0.155, p < 0.001), insulin (ß = -0.099, p = 0.034), triglycerides (ß = -0.166, p < 0.001), VLDL triglycerides (ß = -0.230, p < 0.001), VLDL cholesterol (ß = -0.168, p = 0.001), LDL cholesterol (ß = -0.094, p = 0.046) and HDL triglycerides (ß = -0.149, p = 0.004) and directly related to HDL cholesterol (ß = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (ß = -0.123, p = 0.010), body fat percentage (ß = -0.099, p = 0.027), insulin (ß = -0.108, p = 0.021), triglycerides (ß = -0.144, p = 0.002), VLDL triglycerides (ß = -0.233, p < 0.001) and VLDL cholesterol (ß = -0.199, p < 0.001) and directly related to HDL cholesterol (ß = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (ß = 0.135, p = 0.003), body fat percentage (ß = 0.090, p = 0.039), waist circumference (ß = 0.097, p = 0.033) and systolic blood pressure (ß = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (ß = 0.092, p = 0.049), triglycerides (ß = 0.131, p = 0.005), VLDL triglycerides (ß = 0.134, p = 0.009), VLDL cholesterol (ß = 0.147, p = 0.004) and LDL cholesterol (ß = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors. CONCLUSIONS: The results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01803776.

Cardiovascular fitness and haemodynamic responses to maximal cycle ergometer exercise test in children 6-8 years of age.

We investigated cardiovascular fitness and haemodynamic responses to maximal cycle ergometer exercise test in children. The participants were a population sample of 425 children (204 girls, 221 boys) aged 6-8 years. Heart rate (HR) and systolic blood pressure (SBP) were measured from the beginning of pre-exercise rest to the end of recovery period. We provided reference values for peak workload and changes in HR and SBP during and after maximal exercise test in girls and boys. Girls had a lower cardiovascular fitness, indicated by peak workload per body weight [mean (2 s) 2.7 (0.9) vs. 3.1 (1.0) W · kg(-1), P < 0.001] and lean mass [mean (2 s) 3.5 (0.9) vs. 3.8 (1.0) W · kg(-1), P < 0.001] than boys. Plateau or decline in SBP close to the end of the test was found in about third of children and was considered a normal SBP response. Girls had a slower HR decrease within 2 min after the test than boys [mean (2 s) 53 (18) vs. 59 (22) beats · min(-1), P < 0.001]. The results are useful for physicians and exercise physiologists to evaluate cardiovascular fitness and haemodynamic responses to exercise in children and to detect children with low exercise tolerance or abnormal haemodynamic responses to exercise.

Point-of-care ß-hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG-PET/CT.

AIMS: The aims of our study were to evaluate whether point-of-care ß-hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac [18F]-fluoro-2-deoxy-d-glucose-positron emission tomography with computerized tomography (FDG-PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. METHODS AND RESULTS: We recruited 193 patients with any clinical indication for whole body [18F]-FDG-PET/CT. BHB level was measured with a point-of-care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point-of-care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography were measured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut-off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). CONCLUSIONS: BHB level measured with a point-of-care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.

Heparin does not improve myocardial glucose metabolism suppression in [18 F]FDG PET/CT in patients with low ß-hydroxybutyrate level.

BACKGROUND: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of ß-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT. RESULTS: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15-20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1-5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875). CONCLUSIONS: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.

Metabolic risk factors are associated with stiffness index, reflection index and finger skin temperature in children--Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: Childhood metabolic syndrome (MetS) has been found to predict adulthood MetS, type 2 diabetes and cardiovascular disease, emphasizing the early identification of children at increased risk of these diseases. Children with clustering of metabolic risk factors have been reported to have a mild arterial stiffness and endothelial dysfunction, but limited evidence is available from population-based samples of children. METHODS AND RESULTS: The associations of metabolic risk factors with arterial stiffness, tone and endothelial function were studied in 173 prepubertal children (90 girls) 6-8 years of age. MetS was assessed both by continuous MetScore and dichotomously. Stiffness index (SI), reflection index (RI) and finger skin temperature (FST) were measured before and after maximum exercise test, and percent change was calculated for RI (RI%Δ) and FST (FST%Δ). MetScore (r=0.26, P=0.001), fasting insulin (r=0.24, P=0.002), fasting triglycerides (r=0.20, P=0.009), systolic (SBP; r=0.24, P=0.002) and diastolic blood pressure (DBP; r=0.19, P=0.013) correlated with SI. MetScore (r=-0.17, P=0.024, r=0.21, P=0.006), waist circumference (r=-0.19, P=0.012, r=0.23, P=0.003) and SBP (r=-0.16, P=0.035, r=0.21, P=0.005) correlated with RI and FST. High-density lipoprotein cholesterol correlated with FST (r=-0.22, P=0.004) and FST%Δ (r=-0.24, P=0.002). RI decreased and FST increased with exercise (P<0.001). Waist circumference correlated inversely with RI%Δ in boys (r=-0.22, P=0.046) and directly with RI%Δ in girls (r=0.27, P=0.011). CONCLUSIONS: Metabolic risk factors are associated with arterial stiffness, tone and endothelial function in prepubertal children.

Craniofacial morphology but not excess body fat is associated with risk of having sleep-disordered breathing--the PANIC Study (a questionnaire-based inquiry in 6-8-year-olds).

UNLABELLED: We investigated the associations of dental occlusion, other craniofacial features and body fat with paediatric sleep-disordered breathing (SDB) in a representative population sample of 491 Finnish children 6-8 years of age. Overweight and obesity were defined using age- and sex-specific body mass index cutoffs by International Obesity Task Force (IOTF) criteria. Body fat percentage was assessed by dual-energy X-ray absorptiometry. Facial proportions, dental occlusion and soft tissue structures were evaluated by an orthodontist. Sleep was assessed by a sleep questionnaire administered by the parents. SDB was defined as apnoeas, frequent or loud snoring or nocturnal mouth breathing observed by the parents. The prevalence of SDB was 9.9 % with no difference between boys and girls. The median (interquartile range) of body fat percentage was 20.6 (17.4-27.1) in girls and 15.0 (11.4-21.6) in boys. Altogether 11.4 % of boys and 15.6 % of girls were classified as having overweight or obesity according to the IOTF criteria. There was no difference in the prevalence of overweight, obesity or body fat percentage between children with SDB and those without it. Children with tonsillar hypertrophy had a 3.7 times higher risk of suffering SDB than those with normal size tonsils after adjustment for age, sex and body fat percentage. Furthermore, children with cross bite had a 3.3 times higher risk of having SDB than those without cross bite, and children with a convex facial profile had a 2.6 times higher risk of having SDB than those with a normal facial profile. CONCLUSION: Abnormal craniofacial morphology, but not excess body fat, is associated with an increased risk of having SDB in 6-8-year-old children. A simple model of necessary clinical examinations (i.e. facial profile, dental occlusion and tonsils) is recommended to recognize children with an increased risk of SDB.

Is low cardiorespiratory fitness a feature of metabolic syndrome in children and adults?

OBJECTIVES: Cardiorespiratory fitness has been inversely associated with risk of cardiometabolic diseases. However, there are no studies comparing the independent associations of cardiorespiratory fitness scaled by body size and composition using different approaches with cardiometabolic risk factors between children and adults. We therefore investigated these associations in children and adults using same measures for cardiorespiratory fitness and cardiometabolic risk factors. DESIGN: Cross-sectional. METHODS: A total of 352 children (47.2 % girls) and 572 men were included in the study. Peak oxygen uptake (V̇O2peak) was measured during a maximal exercise test on a cycle ergometer and was scaled by total body mass, total fat free mass, and allometrically modelled body mass, fat free mass, and stature. Insulin, glucose, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were assessed from fasting blood samples and systolic blood pressure and diastolic blood pressure were measured. Homeostatic model assessment for insulin resistance and continuous metabolic risk score were computed. RESULTS: V̇O2peak scaled by body mass was inversely associated with insulin, homeostatic model assessment for insulin resistance, triglycerides, diastolic blood pressure, the cardiometabolic risk score and the number of cardiometabolic risk factors in children and adults. However, these associations attenuated remarkably when V̇O2peak was scaled by total fat free mass or allometrically modelled body mass, fat free mass, or stature. V̇O2peak was consistently and positively associated with high-density lipoprotein cholesterol in children and adults irrespective of the scaling approach. CONCLUSIONS: The inverse associations of cardiorespiratory fitness with cardiometabolic risk factors among children and adults attenuated remarkably when body size and composition were appropriately controlled for. However, the positive association between cardiorespiratory fitness and high-density lipoprotein cholesterol was consistent irrespective of the scaling approach.

Cross-sectional associations between cardiorespiratory fitness and NMR-derived metabolic biomarkers in children - the PANIC study.

Objective: Cardiorespiratory fitness has been inversely associated with cardiovascular risk across the lifespan. Some studies in adults suggest that higher cardiorespiratory fitness is associated with cardioprotective metabolite profile, but the evidence in children is lacking. Therefore, we investigated the cross-sectional association of cardiorespiratory fitness with serum nuclear magnetic resonance derived metabolic biomarkers in children. Methods: A population sample of 450 children aged 6-8 years was examined. Cardiorespiratory fitness was assessed by a maximal exercise test on a cycle ergometer and quantified as maximal power output normalised for lean body mass assessed by dual-energy X-ray absorbtiometry. Serum metabolites were assessed using a high throughput nuclear magnetic resonance platform. The data were analysed using linear regression analyses adjusted for age and sex and subsequently for body fat percentage (BF%) assessed by DXA. Results: Cardiorespiratory fitness was directly associated with high density lipoprotein (HDL) cholesterol (ß=0.138, 95% CI=0.042 to 0.135, p=0.005), average HDL particle diameter (ß=0.102, 95% CI=0.004 to 0.199, p=0.041), and the concentrations of extra-large HDL particles (ß=0.103, 95% CI=0.006 to 0.201, p=0.038), large HDL particles (ß=0.122, 95% CI=0.025 to 0.220, p=0.014), and medium HDL particles (ß=0.143, 95% CI=0.047 to 0.239, p=0.004) after adjustment for age and sex. Higher cardiorespiratory fitness was also associated with higher concentrations of ApoA1 (ß=0.145, 95% CI=0.047 to 0.242, p=0.003), glutamine (ß=0.161, 95% CI=0.064 to 0.257, p=0.001), and phenylalanine (ß=0.187, 95% CI=0.091 to 0.283, p<0.001). However, only the direct associations of cardiorespiratory fitness with the concentrations of HDL cholesterol (ß=0.114, 95% CI=0.018 to 0.210, p=0.021), medium HDL particles (ß=0.126, 95% CI=0.030 to 0.223, p=0.010), ApoA1 (ß=0.126, 95% CI=0.030 to 0.223, p=0.011), glutamine (ß=0.147, 95% CI=0.050 to 0.224, p=0.003), and phenylalanine (ß=0.217, 95% CI=0.122 to 0.311, p<0.001) remained statistically significant after further adjustment for BF%. Conclusions: Higher cardiorespiratory fitness was associated with a cardioprotective biomarker profile in children. Most associations were independent of BF% suggesting that the differences in serum metabolites between children are driven by cardiorespiratory fitness and not adiposity.

Changes in body composition by age and obesity status in preschool-aged children: the STEPS study.

BACKGROUND/OBJECTIVES: Obesity in early childhood is associated with increased risk of chronic diseases, but studies of body composition at preschool ages are sparse. Therefore, we examined differences in body composition by sex and obesity status in Finnish preschool-aged children and within-individual changes in body composition in normal and overweight children. SUBJECT/METHODS: Body composition was measured using segmental multifrequency bioimpedance analysis (BIA) in 476 children and in 781 children at age 3 and 5 years, respectively. Of those, 308 had repeated BIA measurements at both ages. BMI-SDS was used for classification of normal weight and overweight children. RESULTS: Sex difference in the amount of lean mass (LM) was already seen at 3 years of age (boys 11.7 kg, girls 11.3 kg; p < 0.001). At 5 years of age, boys had lower fat mass (FM; 3.6 kg vs. 3.9 kg, p < 0.001), lower percent fat mass (%FM; 17.2% vs. 19.1%; p < 0.001), and higher LM (16.0 kg vs. 15.2 kg; p < 0.001) than girls. Overweight children had higher values in FM, %FM, and LM compared with normal weight peers at both ages. Among normal weight children, the increase of LM by age was associated with only minor changes in FM, whereas children who were or became overweight both LM and FM was substantially increased between 3 and 5 years of age. CONCLUSIONS: BIA-assessed body composition differs by sex and obesity status already at age of 3 years. For children who are or become overweight at very young age, the patterns for the changes in LM and FM by age are different than for normal weight children.

Cardiorespiratory Fitness, Physical Activity, and Insulin Resistance in Children.

PURPOSE: Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycemia and insulin resistance and their interactions with physical activity (PA) and sedentary time among 452 children age 6 to 8 yr. METHODS: We assessed CRF with a maximal cycle ergometer exercise test and used allometrically scaled maximal power output (Wmax) for lean body mass (LM) and body mass (BM) as measures of CRF. The BF% and LM were measured by dual-energy X-ray absorptiometry, fasting glycemia by fasting plasma glucose, and insulin resistance by fasting serum insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The PA energy expenditure, moderate-to-vigorous PA (MVPA), and sedentary time were assessed by combined movement and heart rate sensor. RESULTS: Wmax/LM was not associated with glucose (ß = 0.065, 95% confidence interval [CI] = -0.031 to 0.161), insulin (ß = -0.079, 95% CI = -0.172 to 0.015), or HOMA-IR (ß = -0.065, 95% CI = -0.161 to 0.030). Wmax/BM was inversely associated with insulin (ß = -0.289, 95% CI = -0.377 to -0.200) and HOMA-IR (ß = -0.269, 95% CI = -0.359 to -0.180). The BF% was directly associated with insulin (ß = 0.409, 95% CI = 0.325 to 0.494) and HOMA-IR (ß = 0.390, 95% CI = 0.304 to 0.475). Higher Wmax/BM, but not Wmax/LM, was associated with lower insulin and HOMA-IR in children with higher BF%. Children with higher BF% and who had lower levels of MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. CONCLUSIONS: Children with higher BF% together with less MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Cardiorespiratory fitness appropriately controlled for body size and composition using LM was not related to insulin resistance among children.

Adiposity Criteria in Assessing Increased Cardiometabolic Risk in Prepubertal Children.

Objective: Adiposity induces the clustering of cardiometabolic risk factors, and pediatric adiposity is a better indicator for adulthood cardiometabolic diseases than pediatric metabolic syndrome. However, the observed prevalence of pediatric adiposity depends on the methods and cut-points used. Therefore, we aimed to define diagnostic criteria for adiposity which enable more valid identification of prepubertal children at increased cardiometabolic risk. Methods: The participants were 470 prepubertal children (249 boys) aged 6-8 years. The measures of adiposity included body mass index-standard deviation score (BMI-SDS), waist-to-height ratio (WHtR) and body fat percentage (BF%) assessed by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Criteria for adiposity were determined by increased cardiometabolic risk. Cardiometabolic risk factors which correlated with BF% assessed by DXA in the upper but not lower half of BF% (serum insulin and plasma high-density lipoprotein cholesterol, triglycerides, gamma-glutamyl transferase, high-sensitivity C-reactive protein and uric acid) were included in the cardiometabolic risk score (CMS). We computed receiver operating characteristics curves for the measures of adiposity using the ≥90th percentile of CMS as a measure of increased cardiometabolic risk, and local regression curves were graphed to demonstrate the associations of the measures of adiposity with CMS. Results: In girls, WHtR of 0.445 (area under curve 0.778, its 95% confidence interval 0.65-0.91, sensitivity and specificity 0.73) and BF% of 19.5% assessed by BIA (0.801, 0.70-0.90, 0.73) were the best overall criteria for increased cardiometabolic risk. In boys, BMI-SDS of 0.48 (0.833, 0.75-0.92, 0.76) was the best overall criterion for increased cardiometabolic risk. While local regression curves in girls showed that WHtR of 0.445 corresponds well to a point where CMS began to increase, in boys local regression curves suggest that CMS began to increase even at a lower level of BMI-SDS than 0.48. Moreover, the diagnostic ability of the measures of adiposity to exclude increased cardiometabolic risk was poorer than the ability to detect it. Conclusions: In general, the measures of adiposity have sufficient diagnostic accuracy to be utilized as the screening tool for increased cardiometabolic risk. The observed cut-points for adiposity were lower than the traditional cut-points for adiposity.