Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators.

AIMS: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. MATERIALS AND METHODS: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. RESULTS: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%-25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%-7%) and high triglyceride levels (2%-6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%-2%). CONCLUSIONS: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%-40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.

Accelerometer-derived physical activity and sedentary behaviors in individuals with newly diagnosed type 2 diabetes: A cross-sectional study from the Danish nationwide DD2 cohort.

Introduction: Habitual physical activity behaviors of individuals with new-onset type 2 diabetes are largely unknown. We aimed to investigate accelerometer-derived physical activity behaviors in individuals with newly diagnosed type 2 diabetes. We also examined sociodemographic and health-related correlates of a high-risk physical activity profile. Methods: This cross-sectional study used data from 768 participants enrolled in an intervention study nested within the Danish Centre for Strategic Research in Type 2 diabetes (DD2) cohort. Physical activity was assessed by 24-h dual monitor accelerometry. Prevalence ratios of having a high-risk physical activity profile were estimated using Poisson regression adjusted for age and sex. Results: Study participants spent on average 9.7 (25th and 75th percentiles, 8.3; 11.1) hours/day sitting, walked for 1.1 (0.8; 1.6) hours/day and accumulated 4,000 (2,521; 5,864) steps/day. Still, 62% met the recommendations for physical activity. Characteristics associated with a high-risk physical activity profile (observed in 24.5% of participants) included older age, higher body mass index (BMI), unemployment, retirement, comorbidities, and current smoking. Hence, participants aged 60-69, 70-79 and 80+ years had prevalence ratios of 2.12 (95% CI 1.31; 3.42), 1.99 (1.18; 3.34) and 3.09 (1.42; 6.75) for a high-risk activity profile, respectively, versus participants <50 years. BMI values of 30-39 and 40+ were associated with 1.83 (1.06; 3.15) and 3.38 (1.88; 6.05) higher prevalence ratios compared to normal-weight. Unemployment or retirement was associated with 1.62 (1.09; 2.41) and 2.15 (1.37; 3.39) times higher prevalence ratios, compared to individuals in the working force. Having a Charlson Comorbidity Index score of 1-2 or 3+ was associated with 1.36 (1.03-1.79) and 1.90 (1.27-1.84) higher prevalence ratios, while current smoking was associated with a prevalence ratio of 1.72 (1.25; 2.35) compared to never smokers. Conclusion: This study shows that 62% of individuals with newly diagnosed type 2 diabetes met the recommendations for physical activity. Still, the majority of participants were also highly sedentary and accumulated very few daily steps, emphasizing the need for focusing on both increasing physical activity and reducing sedentary behaviors in the prevention of diabetes-related complications. Individuals with a high-risk physical activity profile were characterized by more obesity, socioeconomic inequalities, advanced age and comorbidities.Trial registration number: NCT02015130.

Exposure to perfluoroalkylated substances (PFAS) in relation to fitness, physical activity, and adipokine levels in childhood: The european youth heart study.

BACKGROUND: perfluoroalkylated substances (PFAS) are highly persistent chemicals that are able to alter the human metabolism - potentially via disruption of cell signaling pathways mediated by adipokines. Both adiponectin and leptin are influenced by and exert influence on energy storage and energy expenditure, wherefore associations between PFAS and adipokines may be mediated by fitness and fat mass. OBJECTIVES: the aim of this cross-sectional study was to investigate the association between childhood exposure to PFAS and adipokines (adiponectin and leptin), while considering associations between PFAS and children's level of fitness, physical activity and fat mass to elucidate potential mediation by fitness, physical activity and fat mass. METHODS: 9-year old children from Danish public schools were recruited in the European Youth Heart Study in 1997. For this study only children with valid measures on PFAS (PFOS, PFOA, PFNA, PFDA and PFHxS), adipokines (adiponectin and leptin), fitness, fat mass and co-variates (parity and maternal income) were included (N = 242). Multiple linear regression models with and without conditioning and causal mediation analysis were applied. RESULTS: this study found inverse associations between PFOA, PFDA and PFHxS and leptin. PFOA was positively associated with adiponectin, whereas PFHxS was inversely associated with adiponectin in boys. Latter association seemed to be mediated by fat mass. Associations with leptin showed indirect effects of fitness and fat mass but were unable to demonstrate significant mediation. Neither PFOS nor PFNA were associated with the outcome. DISCUSSION: these results may indicate a favorable leptin profile with increasing PFAS, although the results could be driven by residual negative confounding from socio-economic factors and mediation by fitness and fat mass.

Higher circulating plasma polychlorinated biphenyls (PCBs) in fit and lean children: The European youth heart study.

BACKGROUND: Lipophilic compounds such as polychlorinated biphenyls (PCBs) are primarily stored in adipose tissue, but exercise-induced lipolysis is able to release PCBs from the adipose tissue into the circulation. The plasma concentration, distribution and metabolism of PCBs can thus vary much among individuals due to inter-human variations in lifestyle behavior and pharmacokinetics. OBJECTIVES: We examined the observational relationship of circulating plasma PCB concentrations with cardiorespiratory fitness, engagement in vigorous physical activity and fat mass in a healthy Danish child population. METHODS: Data on ∑PCB (PCB138, PCB153 and PCB180), cardiorespiratory fitness, skinfold thickness and objectively measured physical activity of 509 children derived from the Danish sub-study of The European Youth Heart Study. RESULTS: Higher fitness and greater leanness were associated with elevated plasma ∑PCB in both boys and girls. The associations were independent of each other and persisted after controlling for socio-economic status and duration of breastfeeding. We observed an almost three-fold increase in plasma ∑PCB level in the most fit/least fat children relative to the least fit/most fat children. The association between fatness and ∑PCB was strongest for boys as girls, and especially pubertal girls, displayed lower decrease in plasma ∑PCB with higher fat mass. DISCUSSION: Our findings suggest that increased lipolysis stimulates the release of PCBs into the vasculature. The consequence is higher plasma levels of PCB in very fit and lean subjects. This scenario is likely to cause negative confounding in epidemiological observations of PCB and cardio-metabolic health. At the same time adipose tissue may play a dual role in promoting adverse health and providing a relatively safe place to store PCB.

Reference values for cardiometabolic risk scores in children and adolescents: Suggesting a common standard.

BACKGROUND AND AIMS: International reference values for cardiometabolic risk variables, to allow for standardization of continuous risk scores in children, are not currently available. The aim of this study was to provide international age- and gender-specific reference values for cardiometabolic risk factors in children and adolescents. METHODS: Cohorts of children sampled from different parts of Europe (North, South, Mid and Eastern) and from the United States were pooled. In total, 22,479 observations (48.7% European vs. 51.3% American), 11,234 from girls and 11,245 from boys, aged 6-18 years were included in the study. Linear mixed-model regression analysis was used to analyze the associations between age and each cardiometabolic risk factor. RESULTS: Reference values for 14 of the most commonly used cardiometabolic risk variables in clustered risk scores were calculated and presented by age and gender: systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), body mass index (BMI), sum of 4 skinfolds (sum4skin), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TC:HDL-C ratio, glucose, insulin, homeostatic model assessment-score (HOMA-score), and cardiorespiratory fitness (CRF). CONCLUSIONS: This study suggests a common standard to define cardiometabolic risk in children. Adapting this approach makes single risk factors and clustered cardiometabolic disease risk scores comparable to the reference material itself and comparable to cardiometabolic risk values in studies using the same strategy. This unified approach therefore increases the prospect to estimate and compare prevalence and trends of cardiometabolic risk in children when using continuous cardiometabolic risk scores.

Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later: The European Youth Heart Study.

OBJECTIVE: To investigate the long-term association of exposure to perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15 years) on indicators of adiposity and glucose metabolism in adolescence (15 years) and young adulthood (21 years). Secondarily, we aim to clarify the degree of tracking of exposure from childhood into young adulthood. RESEARCH DESIGN AND METHODS: Data derived from a large multicenter prospective cohort study, in which the same participants have been observed from childhood (N = 590), during adolescence (N = 444), and into young adulthood (N = 369). Stored plasma samples were analyzed for PFOS and PFOA. Indicators of adiposity comprising body height, body weight, sum of four skinfolds, and waist circumference, as well as indicators of glucose metabolism, comprising fasting blood glucose, triglyceride, and insulin levels, ß-cell function, and insulin resistance, have been collected at all study waves. Multiple linear regression was applied in order to model earlier exposure on later outcome while controlling for baseline outcome levels, sex, age, and socioeconomic factors. RESULTS: Childhood exposure to PFOS was associated with indicators of adiposity at 15 years of age that are displayed in elevated BMI, skinfold thickness, and waist circumference, as well as increased skinfold thickness and waist circumference at 21 years of age. PFOA exposure in childhood was associated with decreased ß-cell function at 15 years of age. We did not observe associations between exposure during adolescence and indicators of adiposity and glucose metabolism in young adulthood. CONCLUSIONS: This study found evidence for childhood exposure to PFOS and PFOA predicting adiposity at 15 and 21 years of age and impaired ß-cell function at 15 years of age, respectively.

Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents.

OBJECTIVES: To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents. METHODS: The design was cross-sectional. A convenient sample of 869 sixth and seventh grade students (12-14 years) was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical activity was assessed with GT3X and GT3X+ accelerometers presented in sex-specific quartiles of mean counts per minute and mean minutes per day in moderate-to-vigorous physical activity. Active commuting and sports participation was self-reported. Mixed model regression was applied. Total physical activity level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer. RESULTS: Non-cyclists in the 2nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2nd and 3rd quartile of moderate-to-vigorous physical activity relative to the least active quartile. Non-cyclists in the 3rd quartile of counts per minute had an improved reaction time and cyclists in the 2nd quartile of counts per minute and moderate-to-vigorous physical activity displayed an improved accuracy, whereas non-cyclists in the 2nd quartile of counts per minute showed an inferior accuracy relative to the least active quartile. Bicycling to school and organized sports participation were positively associated with mathematic performance. CONCLUSIONS: Sports participation and bicycling were positively associated with mathematic performance. Results regarding objectively measured physical activity were mixed. Although, no linear nor dose-response relationship was observed there was no indication of a higher activity level impairing the scholastic or cognitive performance.