Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial.

Long-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health, but the underlying molecular mechanisms remain poorly understood. To address this knowledge gap, we conducted an 8-year diet and physical activity intervention in a general population of children. The research revealed that the intervention influenced 80 serum metabolites over two years, with 17 metabolites continuing to be affected after eight years. The intervention primarily impacted fatty amides, including palmitic amide, linoleamide, oleamide, and others, as well as unsaturated fatty acids, acylcarnitines, phospholipids, sterols, gut microbiota-derived metabolites, amino acids, and purine metabolites. Particularly noteworthy were the pronounced changes in serum fatty amides. These serum metabolite alterations could represent molecular mechanisms responsible for the observed benefits of long-term lifestyle interventions on cardiometabolic and overall health since childhood. Understanding these metabolic changes may provide valuable insights into the prevention of cardiometabolic and other non-communicable diseases since childhood.

Physical activity volume and intensity distribution in relation to bone, lean and fat mass in children.

Considering physical activity (PA) volume and intensity may provide novel insights into the relationships of PA with bone, lean, and fat mass. This study aimed to assess the associations of PA volume, PA intensity distribution, including moderate-to-vigorous PA (MVPA) with total-body-less-head bone mineral content (BMC), lean, and fat mass in children. A population sample of 290 Finnish children (158 females) aged 9-11 years from the Physical Activity and Nutrition in Children (PANIC) Study was studied. PA, including MVPA, was assessed with a combined heart rate and movement sensor, and the uniaxial acceleration was used to calculate average-acceleration (a proxy metric for PA volume) and intensity-gradient (reflective of PA intensity distribution). Linear regression analyzed the associations of PA volume, PA intensity and MVPA with BMC, lean mass, and fat mass assessed by dual-energy X-ray absorptiometry. PA volume was positively associated with BMC in females (unstandardised regression coefficient [ß] = 0.26) and males (ß = 0.47), and positively associated with lean (ß = 7.33) and negatively associated with fat mass in males (ß = -20.62). PA intensity was negatively associated with BMC in males (ß = -0.13). MVPA was positively associated with lean mass in females and males (ß = 0.007 to 0.012), and negatively associated with fat mass in females and males (ß = -0.030 to -0.029). PA volume may be important for improving BMC in females and males, and increasing lean and reducing fat mass in males, whereas MVPA may be important for favorable lean and fat outcomes in both sexes.

The Mediating Role of Endocrine Factors in the Positive Relationship Between Fat Mass and Bone Mineral Content in Children Aged 9-11 Years: The Physical Activity and Nutrition in Children Study.

Introduction: We aimed to investigate whether the relationship between fat mass and bone mineral content (BMC) is mediated by insulin, leptin, adiponectin, dehydroepiandrosterone sulphate, testosterone and estradiol in children aged 9-11 years. Materials and Methods: We utilised cross-sectional data from the Physical Activity and Nutrition in Children study (n = 230 to 396; 112 to 203 girls). Fat mass and BMC were assessed with dual-energy X-ray absorptiometry. Endocrine factors were assessed from fasted blood samples. We applied the novel 4-way decomposition method to analyse associations between fat mass, endocrine factors, and BMC. Results: Fat mass was positively associated with BMC in girls (ß = 0.007 to 0.015, 95% confidence interval (CI) 0.005 to 0.020) and boys (ß = 0.009 to 0.015, 95% CI 0.005 to 0.019). The relationship between fat mass and BMC was mediated by free leptin index in girls (ß = -0.025, 95% CI -0.039 to -0.010) and boys (ß = -0.014, 95% CI -0.027 to -0.001). The relationship between fat mass and BMC was partially explained by mediated interaction between fat mass and free leptin index in boys (ß = -0.009, 95% CI -0.013 to -0.004) and by interaction between fat mass and adiponectin in girls (ß = -0.003, 95% CI -0.006 to -0.000). Conclusion: At greater levels of adiponectin and free leptin index, the fat mass and BMC relationship becomes less positive in girls and boys respectively. The positive association between fat mass with BMC was largely not explained by the endocrine factors we assessed. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT01803776], identifier NCT01803776.

The Positive Relationship between Moderate-to-Vigorous Physical Activity and Bone Mineral Content Is Not Mediated by Free Leptin Index in Prepubertal Children: The PANIC Study.

PURPOSE: Moderate-to-vigorous physical activity (MVPA) positively influences bone mineral content (BMC) in prepubertal children, but it is unknown whether this relationship is partially mediated by free leptin index. The aim of this study was to examine whether the relationship between MVPA and total body less head (TBLH) BMC is mediated or moderated by free leptin index in prepubertal children. METHODS: We performed a cross-sectional analysis on 401 children (194 girls) from baseline examinations of the Physical Activity and Nutrition in Childhood Study. We applied the four-way decomposition mediation analysis method to assess whether free leptin index, measured from fasted blood samples, mediated the relationship between accelerometer-measured MVPA and TBLH BMC measured by dual-energy X-ray absorptiometry. RESULTS: MVPA had a positive controlled direct effect on TBLH BMC in girls and boys (ß = 0.010 to 0.011, p < 0.05). There was no mediation or interaction between MVPA, free leptin index and TBLH BMC in girls or boys (ß = -0.000 to 0.001, p > 0.05). CONCLUSION: Our study indicates that MVPA positively influences TBLH BMC through pathways not related to free leptin index in predominantly normal-weight prepubertal children, likely primarily through mechanical loading. The relationships between MVPA, free leptin index and TBLH BMC may be influenced by other factors such as pubertal status and adiposity, so it is unknown whether these observations extend to overweight and obese children at different stages of puberty.

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.

Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6-8years of age - The Physical Activity and Nutrition in Children (PANIC) study.

Lean body mass (LM) has been positively associated with bone mineral density (BMD) in children and adolescents, but the relationship between body fat mass (FM) and BMD remains controversial. Several biomarkers secreted by adipose tissue, skeletal muscle, or bone may affect bone metabolism and BMD. We investigated the associations of LM, FM, and such biomarkers with BMD in children. We studied a population sample of 472 prepubertal Finnish children (227 girls, 245 boys) aged 6-8years. We assessed BMD, LM, and FM using whole-body dual-energy x-ray absorptiometry and analysed several biomarkers from fasting blood samples. We studied the associations of LM, FM, and the biomarkers with BMD of the whole body excluding the head using linear regression analysis. LM (standardized regression coefficient ß=0.708, p<0.001), FM (ß=0.358, p<0.001), and irisin (ß=0.079, p=0.048) were positive correlates for BMD adjusted for age, sex, and height in all children. These associations remained statistically significant after further adjustment for LM or FM. The positive associations of dehydroepiandrosterone sulphate (DHEAS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), leptin, free leptin index, and high-sensitivity C-reactive protein and the negative association of leptin receptor with BMD were explained by FM. The positive associations of DHEAS and HOMA-IR with BMD were also explained by LM. Serum 25-hydroxyvitamin D was a positive correlate for BMD adjusted for age, sex, and height and after further adjustment for FM but not for LM. LM and FM were positive correlates for BMD also in girls and boys separately. In girls, insulin, HOMA-IR, leptin, and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height, and FM, none of the biomarkers was associated with BMD. In boys, leptin and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height and FM, 25(OH)D was positively and IGF-1 and leptin were negatively associated with BMD. FM strongly modified the association between leptin and BMD. LM but also FM were strong, independent positive correlates for BMD in all children, girls, and boys. Irisin was positively and independently associated with BMD in all children. The associations of other biomarkers with BMD were explained by LM or FM.

Comparison between parameters from maximal cycle ergometer test first without respiratory gas analysis and thereafter with respiratory gas analysis among healthy prepubertal children.

It is important to distinguish true and clinically relevant changes and methodological noise from measure to measure. In the clinical practice, maximal cycle ergometer tests are typically performed first without respiratory gas analysis and thereafter, if needed, with respiratory gas analysis. Therefore, we report a comparison of parameters from maximal cycle ergometer exercise tests that were done first without respiratory gas analysis and thereafter with it in 38 prepubertal and healthy children (20 girls, 18 boys). The Bland-Altman method was used to assess agreement in maximal workload (WMAX), heart rate (HR), and systolic blood pressure (SBP) between rest and maximum. Girls achieved higher WMAX in the exercise tests with respiratory gas analysis compared with exercise tests without respiratory gas analysis (p = 0.016), whereas WMAX was similar in the tests among boys. Maximal HR (proportional offset, -1%; coefficients of variation, 3.3%) and highest SBP (proportional offset, 3%; coefficients of variation, 10.6%) were similar in the tests among children. Precision and agreement for HR improved and precision for SBP worsened with increasing exercise intensity. Heteroscedasticity was not observed for WMAX, HR, or SBP. We conclude that maximal cycle ergometer tests without and with respiratory gas analysis can be used consecutively because measurement of respiratory gases did not impair performance or have a significant effect on the maximality of the exercise tests. Our results suggest that similar references can be used for children who accept or refuse using a mask during a maximal exercise test.

Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study.

We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5·9 (sd 2·1) µg/d. Altogether, 40·8 % of children used no vitamin D supplements. Of all children, 82·4 % did not meet the recommended total vitamin D intake of 10 µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48·7 % of daily intake. S-25(OH)D was <50 nmol/l in 19·5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient ß=0·262; P<0·001), girls (ß=0·214; P=0·009) and boys (ß=0·257; P=0·003) in multivariable models. Vitamin D intake from supplements (ß=0·171; P=0·035) and age (ß=-0·198; P=0·015) were associated with S-25(OH)D in girls. Children who drank ≥450 g/d of milk, spent ≥2·2 h/d in physical activity, had ≥13·1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S-25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products.