Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans.

According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.

Associations of Serum Irisin and Fibroblast Growth Factor-21 Levels With Bone Mineral Characteristics in Eumenorrheic Adolescent Athletes With Different Training Activity Patterns.

PURPOSE: To describe serum irisin and fibroblast growth factor-21 (FGF-21) concentrations in healthy female adolescents with different training activity patterns and their associations with bone mineral properties and metabolic markers. METHODS: A total of 62 adolescent girls aged 14-18 years were recruited: 22 rhythmic gymnasts, 20 swimmers, and 20 untrained controls. Bone mineral characteristics by dual-energy X-ray absorptiometry, daily energy intake by dietary recall, serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen were measured in all girls. RESULTS: Whole body and lumbar spine areal bone mineral density and lumbar spine bone mineral content were higher in the rhythmic gymnasts group compared with swimmers and untrained controls groups (P < .05). Serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen levels were not significantly different between the groups. In the rhythmic gymnasts group, serum FGF-21 concentration was positively correlated with lumbar spine areal bone mineral density independently of confounding factors (r = .51; P = .027). CONCLUSIONS: Serum irisin and FGF-21 levels were not different between adolescent eumenorrheic girls with different training activity patterns. FGF-21 was positively associated with lumbar spine areal bone mineral density, which predominantly consists of trabecular bone in adolescent rhythmic gymnasts.

Pubertal increment in insulin resistance is negatively related to lumbar bone mineral density in 18-year-old males.

Transient insulin resistance seen during puberty is expected to favour body growth, but our results show that increment in insulin resistance even in physiological ranges during puberty might compromise lumbar spine bone mineral density accrual independently of body composition parameters, and therefore adult bone quality might be challenged. INTRODUCTION: Insulin resistance (IR) might have a compromising effect on growing bone, and therefore adult bone quality might be challenged. The aim of the present study was to identify whether increases in IR during puberty contribute to bone mineral characteristics in males independently of body composition parameters. METHODS: This is a retrospective cohort-based longitudinal observational study. Data from 85 subjects were included. Boys were studied annually during their pubertal years (12 years at baseline) and at follow-up at the age of 18 years. Anthropometry, bone age, fasting blood samples, body composition, total body, and lumbar spine bone mineral characteristics were measured. Insulin resistance was determined by homeostatic model assessment of IR (HOMA-IR). Multiple regression analysis was performed to determine the effect of changes in HOMA-IR during pubertal years as a longitudinal predictor to fixed bone mineral outcome variables at the age of 18 years. All models were adjusted to potential clinically justified confounding variables. RESULTS: After adjustment to baseline bone indices and body composition-related predictors, the pubertal increment in the HOMA-IR was a negative independent predictor of lumbar spine bone mineral areal density (ß = - 0.202, p = 0.005) and lumbar spine bone mineral apparent density (ß = - 0.235, p = 0.005) in 18-year-old males. CONCLUSIONS: Pubertal increment in IR has a potential diminishing effect on lumbar spine bone mineral density accrual independently of body composition parameters. Further studies are needed to clarify whether monitoring HOMA-IR during puberty may identify subjects at increased risk of low peak bone mass and possible osteoporosis in the future.

Arterial Structure in 18-Year-Old Males Is Dependent on Physical Activity at 12 Years and Cumulative Cardiorespiratory Fitness From Puberty to Late Adolescence.

PURPOSE: To evaluate the long-term effect of body composition, physical activity, and cardiorespiratory fitness (CRF) from puberty on arterial health in late adolescent males. METHODS: The cumulative burden of physical activity (measured with accelerometer), CRF (VO2peak0.82), and body composition (body mass index, fat mass, and fat percentage) from puberty to late adolescence (sum of 4 time points from 12 to 18 y) was assessed in 102 males. Additional analysis on the first (T1) and last (T4) time points was performed. Intima-media thickness (IMT), carotid-femoral pulse wave velocity, and augmentation index adjusted to heart rate of 75 beats per minute (bpm) as dependent variables were measured at T4 and analyzed in multivariable regression models adjusted for known risk factors including maturation, blood pressure, and smoking habits. RESULTS: T1 and cumulative body composition measures were independently associated with IMT, while cumulative (ß = -0.011, P = .036) and T4 (ß = -0.0.031, P = .001) CRF revealed independent associations with IMT. Individuals with moderate to vigorous physical activity >60 minutes per day at T1 showed relationship (ß = -1.091, P = .026) with IMT independently of late adolescent physical activity. No significant relationship was present for arterial function. CONCLUSION: Arterial structure in adolescent males is associated with physical activity at 12 years while relationship with CRF can be seen in late adolescence and cumulatively from puberty to late adolescence.

Early DNA methylation changes in children developing beta cell autoimmunity at a young age.

AIMS/HYPOTHESIS: Type 1 diabetes is a chronic autoimmune disease of complex aetiology, including a potential role for epigenetic regulation. Previous epigenomic studies focused mainly on clinically diagnosed individuals. The aim of the study was to assess early DNA methylation changes associated with type 1 diabetes already before the diagnosis or even before the appearance of autoantibodies. METHODS: Reduced representation bisulphite sequencing (RRBS) was applied to study DNA methylation in purified CD4+ T cell, CD8+ T cell and CD4-CD8- cell fractions of 226 peripheral blood mononuclear cell samples longitudinally collected from seven type 1 diabetes-specific autoantibody-positive individuals and control individuals matched for age, sex, HLA risk and place of birth. We also explored correlations between DNA methylation and gene expression using RNA sequencing data from the same samples. Technical validation of RRBS results was performed using pyrosequencing. RESULTS: We identified 79, 56 and 45 differentially methylated regions in CD4+ T cells, CD8+ T cells and CD4-CD8- cell fractions, respectively, between type 1 diabetes-specific autoantibody-positive individuals and control participants. The analysis of pre-seroconversion samples identified DNA methylation signatures at the very early stage of disease, including differential methylation at the promoter of IRF5 in CD4+ T cells. Further, we validated RRBS results using pyrosequencing at the following CpG sites: chr19:18118304 in the promoter of ARRDC2; chr21:47307815 in the intron of PCBP3; and chr14:81128398 in the intergenic region near TRAF3 in CD4+ T cells. CONCLUSIONS/INTERPRETATION: These preliminary results provide novel insights into cell type-specific differential epigenetic regulation of genes, which may contribute to type 1 diabetes pathogenesis at the very early stage of disease development. Should these findings be validated, they may serve as a potential signature useful for disease prediction and management.

Higher circulating EGF levels associate with a decreased risk of IgE sensitization in young children.

BACKGROUND: Decreased exposure to microbial agents in industrialized countries and urban living areas is considered as a risk factor of developing immune-mediated diseases, such as allergies and asthma. Epithelial surfaces in the gastrointestinal and respiratory tracts and in the skin constitute the primary areas in contact with the environmental microbial load. METHODS: We analyzed the levels of 30 cytokines and growth factors in serum or plasma as markers of the immune maturation in the participants in the DIABIMMUNE study from Russian Karelia (n = 60), Estonia (n = 83) and Finland (n = 89), three neighboring countries with remarkable differences in the incidences of allergies, asthma and autoimmune diseases. RESULTS: We observed an upregulation of T helper cell signature cytokines during the first 12 months of life, reflecting natural development of adaptive immune responses. During the first years of life, circulating concentrations of epidermal growth factor (EGF) were significantly higher, especially in Russian children compared with Finnish children. The children who developed IgE sensitization showed lower levels of EGF than those without such responses. CONCLUSION: Our results suggest that low circulating EGF levels associate with the risk of allergies possibly via the effects on the epithelial integrity and mucosal homeostasis.

Effect of supervised sprint interval training on cardiorespiratory fitness and body composition in adolescent boys with obesity.

This study examined the effect of a supervised 12-week sprint interval training (SIT) on cardiorespiratory fitness (CRF) and body composition in adolescent boys with obesity. Twenty-eight adolescents with obesity were allocated to either an intervention group (SIT) (13.1 ± 0.3 yrs; body mass index [BMI]: 30.3 ± 0.9 kg.m-2) or a control group (CONT) (13.7 ± 0.4 yrs; BMI: 32.6 ± 1.6 kg.m-2). The SIT group performed 4-6 × 30s "all-out" cycling bouts, interspersed with 4 min of recovery 3 days a week for 12 weeks. CRF was measured by direct peak oxygen consumption (VO2peak) defined as VO2peak per kg of body mass (mL.min-1kg-1) or by VO2peak per kg of lean body mass (mL.min-1LBM-1) and body composition was assessed by dual-energy X-ray absorptiometry. SIT intervention led to a significant and large between-group difference in VO2peak (p = 0.004; η2 = 0.29). Although SIT group had a significant reduction in body fat percentage (BF%) (from 41.1 ± 1.3% to 39.2 ± 1.5%; p = 0.006), there were no between-group differences in the change of the pre- and post-measures in BF% (p = 0.067). In conclusion, 12-week SIT is effective in increasing CRF and decreasing BF% in adolescent boys with obesity.

Sclerostin, preadipocyte factor-1 and bone mineral values in eumenorrheic adolescent athletes with different training patterns.

INTRODUCTION: The specific aims of the study were to compare possible differences in sclerostin and preadipocyte factor-1 (Pref-1) between rhythmic gymnasts (RG), swimmers (SW) and untrained controls (UC), and to investigate the relationships of sclerostin and Pref-1 with bone mineral characteristics in studied groups. MATERIALS AND METHODS: This study included 62 eumenorrheic adolescents (RG = 22; SW = 20; UC = 20). Bone mineral and body composition characteristics were measured by dual-energy X-ray absorptiometry, and sclerostin, Pref-1, osteocalcin and C-terminal telopeptide of type I collagen (CTx) were measured. RESULTS: Sclerostin was higher (P = 0.001) in RG (129.35 ± 51.01 pg/ml; by 74%) and SW (118.05 ± 40.05 pg/ml; by 59%) in comparison with UC (74.32 ± 45.41 pg/ml), while no differences (P = 0.896) were seen in Pref-1 (RG: 1.42 ± 0.16 ng/ml; SW: 1.41 ± 0.20 ng/ml; UC: 1.39 ± 0.26 ng/ml) between groups. Osteocalcin (RG: 7.74 ± 4.09 ng/ml; SW: 8.05 ± 4.18 ng/ml; UC: 7.04 ± 3.92 ng/ml; P = 0.843) and CTx (RG: 0.73 ± 0.22 ng/ml; SW: 0.64 ± 0.16 ng/ml; UC: 0.62 ± 0.20 ng/ml; P = 0.173) were not different between groups. Sclerostin correlated (P < 0.05) with whole-body bone mineral content (r = 0.61) and lumbar spine (LS) areal bone mineral density (aBMD) (r = 0.43) in RG, and femoral neck aBMD (r = 0.45) in UC. No correlation was found between sclerostin and bone mineral values in SW, and Pref-1 was not correlated with any bone mineral characteristics in studied groups. Sclerostin was the independent variable that explained 14% of the total variance (R2 × 100) in LS aBMD value only in RG. CONCLUSIONS: Adolescent athletes have higher sclerostin compared to UC. Sclerostin was correlated with bone mineral values and predicted areal bone mineral density in RG.

Serum sclerostin and cytokine responses to prolonged sculling exercise in highly-trained male rowers.

This study examined sclerostin and cytokine responses to an endurance training session in male single sculling rowers. Sixteen highly trained rowers performed a 2-h rowing exercise (distance: 23.8 ± 0.9 km; heart rate: 138 ± 8  beats.min-1; intensity: 79.8 ± 2.1% of the anaerobic threshold). Rowing resulted significant increment (p < 0.05) in sclerostin (36%), interleukin (IL)-6 (345%), IL-10 (129%) and monocyte chemoattractant protein-1 (MCP-1) (132%), while increases in irisin (6%) and tumour necrosis factor-α (3%) were not significant (p > 0.05). There was a correlation between the pre-to-post-exercise increase in sclerostin and the distance covered (r = 0.67; p = 0.005) as a marker of energy expenditure, and weekly training volume (r = 0.66; p = 0.005) as a marker of training stress. Post-exercise gain in MCP-1 was the most important predictor of post-exercise gain in sclerostin (ß = 0.543; p = 0.040). In conclusion, acute non-impact rowing training session with a total body mode induced increases in sclerostin and also in IL-6, IL-10 and MCP-1 concentrations, while post-exercise gain in MCP-1 was the main determinant of post-exercise gain in sclerostin. Exercise-induced increase in sclerostin could be regarded as a signal for metabolic reaction to the energy cost of acute exercise in rowers.

A Longitudinal Study of Bone Mineral Accrual during Growth in Competitive Premenarcheal Rhythmic Gymnasts.

The purpose of this investigation was to study whether prolonged competitive rhythmic gymnastics training influenced bone mineral accrual in premenarcheal girls. Eighty-nine girls (45 rhythmic gymnasts [RG] and 44 untrained controls [UC]) between 7 and 9 years of age were recruited and measured annually for four years (not all participants were measured at every occasion). Dual energy x-ray absorptiometry was used to assess the development of whole body (WB), femoral neck (FN) and lumbar spine (LS) bone mineral content (BMC). In addition, body composition, blood adipokine and jumping performance characteristics were obtained. For longitudinal analyses, hierarchical mixed-effects models were constructed to predict differences in the development of WB, FN and LS BMC between RG and UC groups, while accounting for differences in body composition, blood adipokine and jumping performance values. It appeared that from 8 years of age, RG had lower (p < 0.05) fat mass and leptin values, and higher (p < 0.05) jumping performance measures in comparison with UC girls. Hierarchical mixed-effects models demonstrated that RG had 71.9 ± 12.0, 0.23 ± 0.11 and 1.39 ± 0.42 g more (p < 0.05) WB, FN and LS BMC, respectively, in comparison with UC girls. In addition, WB, FN and LS BMC increased more (p < 0.05) between 7 to 12 years of age in RG girls in comparison with UC. In conclusion, these findings suggest that the prolonged exposure to competitive rhythmic gymnastics trainings in premenarcheal girls is associated with greater bone mineral accrual despite lower body fat mass and leptin values.

Contrasting microbiotas between Finnish and Estonian infants: Exposure to Acinetobacter may contribute to the allergy gap.

BACKGROUND: Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. METHODS: We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. RESULTS: Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genus Acinetobacter was more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile of Acinetobacter lwoffii was more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genus Acinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. CONCLUSIONS: In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genus Acinetobacter in the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children.

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort.

BACKGROUND: The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. OBJECTIVE: We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. METHODS: The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5 years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. RESULTS: Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P < .001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. CONCLUSION: Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset.

Rhinoviruses in infancy and risk of immunoglobulin E sensitization.

Previous data about the role of viruses in the development of allergic immunoglobulin E (IgE) sensitization are contradictory. The aim of this study was to determine the possible associations between exposure to different viruses (rhinovirus, enterovirus, norovirus, and parechovirus) during the first year of life and IgE sensitization. Viruses were analyzed from stool samples collected monthly from infants participating in a prospective birth cohort study. From that study, 244 IgE sensitized case children and 244 nonsensitized control children were identified based on their allergen-specific IgE antibody levels at the age of 6, 18, and 36 months. Stool samples (n = 4576) from the case and control children were screened for the presence of rhinovirus, enterovirus, norovirus, and parechovirus RNA by reverse transcription quantitative polymerase chain reaction. The study showed that rhinovirus was the most prevalent virus detected, present in 921 (20%) samples. None of the viruses were associated with IgE sensitization in the full cohort but after stratifying by sex, the number of rhinovirus positive samples was inversely associated with IgE sensitization in boys (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.69-0.94; P = 0.006). There was also a temporal relation between rhinoviruses and IgE sensitization, as rhinovirus exposure during the first 6 months of life was associated with a reduced risk of subsequent IgE sensitization in boys (OR: 0.76; 95% CI: 0.6-0.94; P = 0.016). In conclusion, early exposure to rhinoviruses was inversely associated with IgE sensitization but this protective association was restricted to boys.

Early childhood infections and the use of antibiotics and antipyretic-analgesics in Finland, Estonia and Russian Karelia.

AIM: Infections in early childhood are common reasons to seek medical attention. This study compares the prevalence of infections, and the use of antibiotics and antipyretic-analgesics, in children from Finland, Estonia and Russian Karelia. METHODS: Children with a genetically increased risk for type 1 diabetes (N = 797) were observed from birth up to 3 years of age. Illnesses and medications were reported by parents continuously. All reported infections, antibiotics and antipyretic-analgesics were compared between Finland and Estonia, and to a lesser extent with Russian Karelia, due to poor study compliance. RESULTS: Compared with Estonians, Finns reported more infections during the first and second years of life. During the follow-up, Finnish children had 10 infections while Estonians only had 8 (p < 0.001). Finns also used more antibiotics and antipyretic-analgesics in each year during the follow-up. Russian Karelians reported the lowest frequency of infections and the most infrequent use of antibiotics and antipyretic-analgesics in the first two years of life. CONCLUSION: Infections and the use of antibiotics and antipyretic-analgesics in early childhood were most frequent in Finland, where socio-economic conditions are the most developed and microbial encounters are sparse. This may reflect on the hygiene hypothesis, a less effective immune system that allows normally harmless microbes to attack and cause clinical infections.

Early-life exposure to common virus infections did not differ between coeliac disease patients and controls.

AIM: Our aim was to compare the presence of various common viruses (rhinovirus, enterovirus, adenovirus, Epstein-Barr virus, cytomegalovirus, norovirus, parechovirus) in stool and nasal swab samples as well as virus-specific antibodies in serum samples between children who developed coeliac disease and controls. METHODS: A case-control study was established based on the DIABIMMUNE Study cohorts. During the study, eight Estonian children and 21 Finnish children aged 1.5 years to five years developed coeliac disease and each was matched with a disease-free control. Nasal swabs and stool samples were taken at the age of three to six months and the serum samples at the time of diagnosis. RESULTS: Rhinovirus ribonucleic acid was detected in the nasal swabs from five coeliac disease children, but none of the control children (p = 0.05). There were no statistically significant differences in the level of viral antibodies between cases and controls. Enterovirus immunoglobulin G class antibodies were found more frequently in the Estonian than in the Finnish children (63% versus 23%, p = 0.02). CONCLUSION: This study did not find any marked overall differences in laboratory-confirmed common viral infections between the children who developed coeliac disease and the controls. However, rhinovirus infections were detected slightly more often in those patients who developed coeliac disease.

Physical Activity in Puberty is Associated with Total Body and Femoral Neck Bone Mineral Characteristics in Males at 18 Years of Age.

Background and objectives: Studies indicate that genetic and lifestyle factors influence optimal bone development. Adaptations in bone mineral characteristics related to physical activity (PA) are most often observed in pre- and peri-puberty. Longitudinal associations between bone mineral accrual and objectively measured PA in puberty are poorly understood. The present study aims to investigate whether pubertal PA at different intensities is related to bone mineral characteristics in individuals at 18 years of age. Materials and Methods: Anthropometrics, pubertal stage, bone age and PA by accelerometer were measured in 88 boys at the mean age of 12.1 (T1), 13.1 (T2), 14.0 (T3) and 18.0 years (T4). Different bone mineral parameters were measured by dual-energy X-ray at T4. Stepwise multiple regression analysis was performed to determine the effect of bone age, body mass and PA characteristics on measured bone mineral parameters at 18 years of age. Results: Total PA in puberty together with mean pubertal body mass predicted 35.5% of total body (TB) bone mineral density (BMD), 43.0% of TB less head (LH) bone mineral content (BMC) and 48.1% of BMC/height in individuals at 18 years of age. Vigorous PA and body mass in puberty predicted 43.2% of femoral neck (FN) BMD; bone age at T1, vigorous PA and body mass in puberty predicted 47.3% of FN BMC at 18 years of age. No associations between pubertal PA levels and lumbar spine bone mineral characteristics in individuals at 18 years of age were found. Conclusions: Physical activity in puberty has a significant impact on bone mineral characteristics in individuals at 18 years of age, with total PA being a significant predictor of TB BMD and TB LH BMC as well as BMC/height, whereas vigorous PA is a significant predictor of FN BMD and FN BMC.

The Impact of Physical Activity on Serum Inflammatory Markers in Overweight Pubertal Boys: 24-Month Follow-Up Study.

PURPOSE: To investigate the differences in the pattern of changes in serum inflammatory cytokines measured annually over a 24-month period, between less active and more active overweight boys. PARTICIPANTS/METHODS: In total, 25 pubertal overweight boys were divided by their moderate to vigorous physical activity (MVPA) levels into 2 groups: less active group (LAG; n = 10; MVPA < 60 min/d) and more active group (MAG; n = 15; MVPA > 60 min/d). Physical activity was measured by 7-day accelerometry. Serum concentration of 13 inflammatory cytokines [interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1ß, vascular endothelial growth factor, interferon-γ, tumor necrosis factor-α, monocyte chemotactic protein-1, epidermal growth factor, and C-reactive protein] was measured at baseline (T0), after 12 months (T1), and after 24 months (T2) from fasting blood samples. RESULTS: Serum IL-6 level was significantly higher [LAG: 1.27 (0.86, 1.98) pg/mL; MAG: 0.80 (0.52, 0.84) pg/mL] at T0 and IL-8 level [LAG: 10.26 (8.80, 11.64) pg/mL; MAG: 7.42 (6.10, 9.54) pg/mL] at T2 in LAG compared with MAG. The changes over the study period varied between different inflammatory markers. None of the slopes of any measured markers were statistically different between the LAG and MAG, although the slopes of interferon-γ and IL-10 tended to be different between the groups. CONCLUSIONS: The pattern of changes over the study period varied between different inflammatory markers, but these changes were not different between the MVPA groups. More longitudinal studies are needed to investigate whether IL-6, IL-8, IL-10, and interferon-γ would be the choice of inflammatory markers to study the associations between obesity and physical activity in future.