Developmental models of motor-evoked potential features by transcranial magnetic stimulation across age groups from childhood to adulthood.

To derive the maturation of neurophysiological processes from childhood to adulthood reflected by the change of motor-evoked potential (MEP) features. 38 participants were recruited from four groups (age mean in years [SD in months], number (males)): children (7.3 [4.2], 7(4)), preadolescents (10.3 [6.9], 10(5)), adolescents (15.3 [9.8], 11(5)), and adults (26.9 [46.2], 10(5)). The navigated transcranial magnetic stimulation was performed on both hemispheres at seven stimulation intensity (SI) levels from sub- to supra-threshold and targeted to the representative cortical area of abductor pollicis brevis muscle. MEPs were measured from three hand- and two forearm-muscles. The input-output (I/O) curves of MEP features across age groups were constructed using linear mixed-effect models. Age and SI significantly affected MEP features, whereas the stimulated side had a minor impact. MEP size and duration increased from childhood to adulthood. MEP onset- and peak-latency dropped in adolescence, particularly in hand muscles. Children had the smallest MEPs with the highest polyphasia, whereas I/O curves were similar among preadolescents, adolescents, and adults. This study illustrates some of the changing patterns of MEP features across the ages, suggesting developing patterns of neurophysiological processes activated by TMS, and to motivate studies with larger sample size.

Associations Between Engagement with the BitHabit Digital Lifestyle Intervention and Changes in Type 2 Diabetes Risk Factors.

Type 2 diabetes (T2D) can be prevented or delayed through a healthy lifestyle. Digital behavior change interventions (DBCIs) may offer cost-effective and scalable means to support lifestyle changes. This study investigated associations between user engagement with a habit-formation-based DBCI, the BitHabit app, and changes in T2D risk factors over 12 months in 963 participants at risk of T2D. User engagement was characterized by calculating use metrics from the BitHabit log data. User ratings were used as a subjective measure of engagement. The use metrics and user ratings were the strongest associated with improvements in diet quality. Weak positive associations were observed between the use metrics and changes in waist circumference and body mass index. No associations were found with changes in physical activity, fasting plasma glucose, or plasma glucose two hours after an oral glucose tolerance test. To conclude, increased use of the BitHabit app can have beneficial impacts on T2D risk factors, especially on diet quality.

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%.

Real-world effectiveness of digital and group-based lifestyle interventions as compared with usual care to reduce type 2 diabetes risk - A stop diabetes pragmatic randomised trial.

Background: No real-world randomised controlled trials (RCTs) have explored the effectiveness of lifestyle interventions based on multiple behaviour change theories and using combined digital and group-based face-to-face delivery to improve risk factors for type 2 diabetes (T2D). Methods: We conducted a one-year, multi-centre, unblinded, pragmatic RCT in primary healthcare using the habit formation, self-determination, and self-regulation theories among 2907 adults aged 18-74 years at increased T2D risk randomised into a digital lifestyle intervention group (DIGI, n = 967), a combined digital and group-based lifestyle intervention group (DIGI+GROUP, n = 971), and a control group receiving usual care (CONTROL, n = 969). We collected data on primary outcomes (diet quality by Healthy Diet Index [HDI], physical activity, body weight, fasting plasma glucose, 2-hour plasma glucose) and secondary outcomes (sedentary time, waist circumference, fasting plasma insulin) using digital questionnaires, clinical examinations, fasting blood tests, and 2-hour oral glucose tolerance tests. Main statistical analyses were performed using linear mixed-effects models adjusted for age, sex, and province. This RCT was registered with ClinicalTrials.gov, NCT03156478. Findings: The 2907 participants assigned were recruited between March 1st, 2017, and February 28th, 2018. Diet quality improved more (3·2 vs. 1·4 HDI points, p<0·001 for difference between groups, p'<0·001 for group*time interaction) and waist circumference tended to decrease more (-1·8 vs. -1·3 cm, p = 0·028, p' = 0·068) in DIGI+GROUP than in CONTROL. Fasting insulin tended to increase in CONTROL but not in DIGI (1·0 vs. 0·0 mU/L, p = 0·033, p' = 0·054) or in DIGI+GROUP (1·0 vs. 0·5 mU/L, p = 0·042, p' = 0·054). Good adherence to DIGI and DIGI+GROUP (≥median of 501 habits/year in DIGI, ≥5 of all 6 sessions in GROUP) was associated with improved diet quality and good adherence to DIGI with increased physical activity and decreased sedentary time. Interpretation: A lifestyle intervention based on multiple behaviour change theories and combined digital and group-based face-to-face delivery improves diet quality and tends to decrease abdominal adiposity and prevent an increase in insulin resistance. Good adherence improves the results of the interventions. Funding: Strategic Research Council at Academy of Finland, Academy of Finland, Novo Nordisk Foundation, and Finnish Diabetes Research foundation.

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.

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.

The effects of an 8-year individualised lifestyle intervention on food consumption and nutrient intake from childhood to adolescence: the PANIC Study.

We aimed to investigate the effects of a long-term, individualised, family-based lifestyle intervention on food consumption and nutrient intake from childhood to adolescence. We conducted an 8-year diet and physical activity intervention study in a population sample of children aged 7-9 years at baseline in 2007-2009. We allocated the participants to the intervention group (n 306) and the control group (n 198). We assessed diet by 4-d food records at baseline, 2-year follow-up and 8-year follow-up. We analysed the data using linear mixed-effects models adjusted for age at baseline and sex. The consumption of vegetables and vegetable oil-based spreads (fat ≥60 %) increased in the intervention group but did not change in the control group (P < 0⋅001 for time×group interaction). The consumption of fruits and berries increased in the intervention group but decreased in the control group (P = 0⋅036). The consumption of high-fat cheese (P = 0⋅029), butter-based spreads (P = 0⋅001) and salty snacks (P = 0⋅028) increased less, and the consumption of low-fat cheese (P = 0⋅004) increased more in the intervention group than in the control group. Saturated fat intake (P = 0⋅001) increased less, and the intakes of dietary fibre (P = 0⋅003), vitamin D (P = 0⋅042) and vitamin E (P = 0⋅027) increased more in the intervention group than in the control group. The intakes of vitamin C (P < 0⋅001) and folate (P = 0⋅001) increased in the intervention group but decreased in the control group. To conclude, individualised, family-based lifestyle intervention altered food choices towards more recommended diet and resulted in enhanced diet quality from childhood to adolescence.

Digitally Supported Lifestyle Intervention to Prevent Type 2 Diabetes Through Healthy Habits: Secondary Analysis of Long-Term User Engagement Trajectories in a Randomized Controlled Trial.

BACKGROUND: Digital health interventions may offer a scalable way to prevent type 2 diabetes (T2D) with minimal burden on health care systems by providing early support for healthy behaviors among adults at increased risk for T2D. However, ensuring continued engagement with digital solutions is a challenge impacting the expected effectiveness. OBJECTIVE: We aimed to investigate the longitudinal usage patterns of a digital healthy habit formation intervention, BitHabit, and the associations with changes in T2D risk factors. METHODS: This is a secondary analysis of the StopDia (Stop Diabetes) study, an unblinded parallel 1-year randomized controlled trial evaluating the effectiveness of the BitHabit app alone or together with face-to-face group coaching in comparison with routine care in Finland in 2017-2019 among community-dwelling adults (aged 18 to 74 years) at an increased risk of T2D. We used longitudinal data on usage from 1926 participants randomized to the digital intervention arms. Latent class growth models were applied to identify user engagement trajectories with the app during the study. Predictors for trajectory membership were examined with multinomial logistic regression models. Analysis of covariance was used to investigate the association between trajectories and 12-month changes in T2D risk factors. RESULTS: More than half (1022/1926, 53.1%) of the participants continued to use the app throughout the 12-month intervention. The following 4 user engagement trajectories were identified: terminated usage (904/1926, 46.9%), weekly usage (731/1926, 38.0%), twice weekly usage (208/1926, 10.8%), and daily usage (83/1926, 4.3%). Active app use during the first month, higher net promoter score after the first 1 to 2 months of use, older age, and better quality of diet at baseline increased the odds of belonging to the continued usage trajectories. Compared with other trajectories, daily usage was associated with a higher increase in diet quality and a more pronounced decrease in BMI and waist circumference at 12 months. CONCLUSIONS: Distinct long-term usage trajectories of the BitHabit app were identified, and individual predictors for belonging to different trajectory groups were found. These findings highlight the need for being able to identify individuals likely to disengage from interventions early on, and could be used to inform the development of future adaptive interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03156478; https://clinicaltrials.gov/ct2/show/NCT03156478. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-6574-y.

Cost-effectiveness of physical activity intervention in children - results based on the Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: We assessed the cost-effectiveness of a 2-year physical activity (PA) intervention combining family-based PA counselling and after-school exercise clubs in primary-school children compared to no intervention from an extended service payer's perspective. METHODS: The participants included 506 children (245 girls, 261 boys) allocated to an intervention group (306 children, 60 %) and a control group (200 children, 40 %). The children and their parents in the intervention group had six PA counselling visits, and the children also had the opportunity to participate in after-school exercise clubs. The control group received verbal and written advice on health-improving PA at baseline. A change in total PA over two years was used as the outcome measure. Intervention costs included those related to the family-based PA counselling, the after-school exercise clubs, and the parents' taking time off to travel to and participate in the counselling. The cost-effectiveness analyses were performed using the intention-to-treat principle. The costs per increased PA hour (incremental cost-effectiveness ratio, ICER) were based on net monetary benefit (NMB) regression adjusted for baseline PA and background variables. The results are presented with NMB and cost-effectiveness acceptability curves. RESULTS: Over two years, total PA increased on average by 108 h in the intervention group (95 % confidence interval [CI] from 95 to 121, p < 0.001) and decreased by 65.5 h (95 % CI from 81.7 to 48.3, p < 0.001) in the control group, the difference being 173.7 h. the incremental effectiveness was 87 (173/2) hours. For two years, the intervention costs were €619 without parents' time use costs and €860 with these costs. The costs per increased PA hour were €6.21 without and €8.62 with these costs. The willingness to pay required for 95 % probability of cost-effectiveness was €14 and €19 with these costs. The sensitivity analyses revealed that the ICER without assuming this linear change in PA were €3.10 and €4.31. CONCLUSIONS: The PA intervention would be cost-effective compared to no intervention among children if the service payer's willingness-to-pay for a 1-hour increase in PA is €8.62 with parents' time costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776. Registered 4 March 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=01803776&cntry=&state=&city=&dist= .

Longitudinal associations of physical activity, sedentary time, and cardiorespiratory fitness with arterial health in children - the PANIC study.

We investigated the longitudinal associations of physical activity (PA), sedentary time (ST), and cardiorespiratory fitness (CRF) with arterial health among children. In our primary analyses, we investigated 245 children (girls 51.8%) aged 6-9 years participating in the baseline examinations who had data on arterial health at 2-year follow-up. We also utilized a subsample of 90 children who had a complete arterial health data at baseline and 2-year follow-up. ST (≤1.5 METs), light PA (>1.5-4 METs), moderate PA (>4-7 METs), vigorous PA (>7METs), and moderate-to-vigorous PA (MVPA, >4 METs) were assessed by combined movement and heart rate monitoring and CRF by maximal exercise testing on a cycle ergometer at baseline and 2-year follow-up. Stiffness index (SI) as a measure of arterial stiffness and change in reflection index during exercise test (DRI) as a measure of arterial dilation capacity were assessed by pulse contour analysis. Two-year change in vigorous PA was associated with DRI in boys but not in girls (p=0.021 for interaction). In a subsample analyses, 2-year changes in MPA, VPA, and MVPA were inversely associated with 2-year change in SI. In conclusion, promoting PA at higher intensities may confer larger benefits on arterial health than reducing ST and increasing LPA.

Primary hand motor representation areas in healthy children, preadolescents, adolescents, and adults.

The development of the organization of the motor representation areas in children and adolescents is not well-known. This cross-sectional study aimed to provide an understanding for the development of the functional motor areas of the upper extremity muscles by studying healthy right-handed children (6-9 years, n = 10), preadolescents (10-12 years, n = 13), adolescents (15-17 years, n = 12), and adults (22-34 years, n = 12). The optimal representation site and resting motor threshold (rMT) for the abductor pollicis brevis (APB) were assessed in both hemispheres using navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed at 110% of the rMT while recording the EMG of six upper limb muscles in the hand and forearm. The association between the motor map and manual dexterity (box and block test, BBT) was examined. The mapping was well-tolerated and feasible in all but the youngest participant whose rMT exceeded the maximum stimulator output. The centers-of-gravity (CoG) for individual muscles were scattered to the greatest extent in the group of preadolescents and centered and became more focused with age. In preadolescents, the CoGs in the left hemisphere were located more laterally, and they shifted medially with age. The proportion of hand compared to arm representation increased with age (p = 0.001); in the right hemisphere, this was associated with greater fine motor ability. Similarly, there was less overlap between hand and forearm muscles representations in children compared to adults (p<0.001). There was a posterior-anterior shift in the APB hotspot coordinate with age, and the APB coordinate in the left hemisphere exhibited a lateral to medial shift with age from adolescence to adulthood (p = 0.006). Our results contribute to the elucidation of the developmental course in the organization of the motor cortex and its associations with fine motor skills. It was shown that nTMS motor mapping in relaxed muscles is feasible in developmental studies in children older than seven years of age.

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.

Associations of cardiorespiratory fitness, adiposity, and arterial stiffness with cognition in youth.

PURPOSE: To investigate the associations of cardiorespiratory fitness, adiposity, and arterial stiffness with cognition in 16- to 19-year-old adolescents. METHODS: Fifty four adolescents (35 girls; 19 boys) participated in the study. Peak oxygen uptake (V̇O2peak ) and peak power output (Wmax ) were measured by the maximal ramp test on a cycle ergometer and ventilatory threshold (VT) was determined with ventilation equivalents. Lean mass (LM) and body fat percentage (BF%) were measured using a bioelectrical impedance analysis. Aortic pulse wave velocity (PWVao) and augmentation index (AIx%) were measured by a non-invasive oscillometric device. Working memory, short term memory, visual learning and memory, paired-associate learning, attention, reaction time, and executive function were assessed by CogState tests. RESULTS: V̇O2peak /LM (ß = 0.36 p = .011) and Wmax /LM (ß = 0.30 p = .020) were positively associated with working memory. Wmax /LM was also positively associated with visual learning (ß = 0.37, p = .009). V̇O2 at VT/LM was positively associated with working memory (ß = 0.30 p = .016), visual learning (ß = 0.31 p = .026), and associated learning (ß = -0.27 p = .040). V̇O2 at VT as % of V̇O2peak , BF%, PWVao, and AIx% were not associated with cognition. CONCLUSION: Cardiorespiratory fitness was related to better cognitive function, while BF% and arterial stiffness were not associated with cognition in adolescents.

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.

Internet-Based Lifestyle Intervention to Prevent Type 2 Diabetes Through Healthy Habits: Design and 6-Month Usage Results of Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes can be prevented through lifestyle changes, but sustainable and scalable lifestyle interventions are still lacking. Habit-based approaches offer an opportunity to induce long-term behavior changes. OBJECTIVE: The purposes of this study were to describe an internet-based lifestyle intervention for people at risk for type 2 diabetes targeted to support formation of healthy habits and explore its user engagement during the first 6 months of a randomized controlled trial (RCT). METHODS: The app provides an online store that offers more than 400 simple and contextualized habit-forming behavioral suggestions triggered by daily life activities. Users can browse, inspect, and select them; report their performances; and reflect on their own activities. Users can also get reminders, information on other users' activities, and information on the prevention of type 2 diabetes. An unblended parallel RCT was carried out to evaluate the effectiveness of the app in comparison with routine care. User engagement is reported for the first 6 months of the trial based on the use log data of the participants, who were 18- to 70-year-old community-dwelling adults at an increased risk of type 2 diabetes. RESULTS: Of 3271 participants recruited online, 2909 were eligible to participate in the RCT. Participants were randomized using a computerized randomization system to the control group (n=971), internet-based intervention (digital, n=967), and internet-based intervention with face-to-face group coaching (F2F+digital, n=971). Mean age of control group participants was 55.0 years, digital group 55.2 years, and F2F+digital 55.2 years. The majority of participants were female, 81.1% (787/971) in the control group, 78.3% (757/967) in the digital group, and 80.7% (784/971) in the F2F+digital group. Of the participants allocated to the digital and F2F+digital groups, 99.53% (1929/1938) logged in to the app at least once, 98.55% (1901/1938) selected at least one habit, and 95.13% (1835/1938) reported at least one habit performance. The app was mostly used on a weekly basis. During the first 6 months, the number of active users on a weekly level varied from 93.05% (1795/1929) on week 1 to 51.79% (999/1929) on week 26. The daily use activity was not as high. The digital and F2F+digital groups used the app on a median of 23.0 and 24.5 days and for 79.4 and 85.1 minutes total duration, respectively. A total of 1,089,555 habit performances were reported during the first 6 months. There were no significant differences in the use metrics between the groups with regard to cumulative use metrics. CONCLUSIONS: Results demonstrate that internet-based lifestyle interventions can be delivered to large groups including community-dwelling middle-aged and older adults, many with limited experience in digital app use, without additional user training. This intermediate analysis of use behavior showed relatively good engagement, with the percentage of active weekly users remaining over 50% at 6 months. However, we do not yet know if the weekly engagement was enough to change the lifestyles of the participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03156478; https://clinicaltrials.gov/ct2/show/NCT03156478.

Associations of cardiometabolic risk factors with heart rate variability in 6- to 8-year-old children: The PANIC Study.

BACKGROUND: Associations of cardiometabolic risk factors with heart rate variability (HRV) in children are unclear. We examined associations of cardiometabolic risk score (CRS) and individual cardiometabolic risk factors with HRV variables in 6- to 8-year-olds. METHODS: The participants were a population-based sample of 443 children participating in baseline measurements of the Physical Activity and Nutrition in Children trial. Cardiometabolic risk factors included waist circumference (WC), insulin, glucose, triglycerides, HDL cholesterol, systolic blood pressure (SBP), and diastolic blood pressure (DBP). CRS was calculated as WC + insulin + glucose + triglycerides - HDL cholesterol + the mean of SBP and DBP. HRV variables (SDNN, RMSSD, HF, LF, LF/HF, Mean RR) were measured using 5-minute electrocardiography at rest and analyzed using the Kubios HRV software. In this cross-sectional study, associations of CRS and individual cardiometabolic risk factors with HRV were investigated using linear regression analyses adjusted for sex and peak height velocity. RESULTS: CRS was negatively associated with RMSSD, HF, Mean RR (P value < .05) and positively with LF/HF (P value = .005). Insulin was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05) and positively with LF/HF (P value = .008). SBP was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05). DBP was negatively associated with SDNN, RMSSD, and Mean RR (P value < .05). WC, glucose, triglycerides, or HDL cholesterol were not associated with HRV variables. CONCLUSIONS: Higher CRS, insulin, and blood pressure were associated with smaller HRV, mainly indicating lower parasympathetic activity, in young children. This knowledge may help improving the clinical management of metabolic syndrome and cardiovascular diseases since childhood.

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.

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.

Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents.

BACKGROUND: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. METHODS: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years. RESULTS: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536). CONCLUSIONS: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.

Functional and structural asymmetry in primary motor cortex in Asperger syndrome: a navigated TMS and imaging study.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.