Changes of omentin-1 and chemerin during 4 weeks of lifestyle intervention and 1 year follow-up in children with obesity.

AIMS: Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce. METHODS: In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs). RESULTS: Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p < 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p < 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p < 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p < 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p < 0.001). CONCLUSION: Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss. TRIAL REGISTRATION: ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.

Obesity Genes and Weight Loss During Lifestyle Intervention in Children With Obesity.

Importance: Genome-wide association studies have identified genetic loci influencing obesity risk in children. However, the importance of these loci in the associations with weight reduction through lifestyle interventions has not been investigated in large intervention trials. Objective: To evaluate the associations between various obesity susceptibility loci and changes in body weight in children during an in-hospital, lifestyle intervention program. Design, Setting, and Participants: Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children (LOGIC), an interventional prospective cohort study, enrolled 1429 children with overweight or obesity to participate in an in-hospital lifestyle intervention program. Genotyping of 56 validated obesity single-nucleotide variants (SNVs) was performed, and the associations between the SNVs and body weight reduction during the intervention were evaluated using linear mixed-effects models for each SNV. The LOGIC study was conducted from January 6, 2006, to October 19, 2013; data analysis was performed from July 15, 2015, to November 6, 2016. Exposures: A 4- to 6-week standardized in-hospital lifestyle intervention program (daily physical activity, calorie-restricted diet, and behavioral therapy). Main Outcomes and Measures: The association between 56 obesity-relevant SNVs and changes in body weight and body mass index. Results: Of 1429 individuals enrolled in the LOGIC Study, 1198 individuals (mean [SD] age, 14.0 [2.2] years; 670 [56%] girls) were genotyped. A mean (SD) decrease was noted in body weight of -8.7 (3.6) kg (95% CI, -15.7 to -1.8 kg), and body mass index (calculated as weight in kilograms divided by height in meters squared) decreased by -3.3 (1.1) (95% CI, -5.4 to -1.1) (both P < .05). Five of 56 obesity SNVs were statistically significantly associated with a reduction of body weight or body mass index (all P < 8.93 × 10-4 corresponding to Bonferroni correction for 56 tests). Compared with homozygous participants without the risk allele, homozygous carriers of the rs7164727 (LOC100287559: 0.42 kg; 95% CI, 0.31-0.53 kg, P = 4.00 × 10-4) and rs12940622 (RPTOR: 0.35 kg; 95% CI, 0.18-0.52 kg; P = 1.86 × 10-5) risk alleles had a lower reduction of body weight, whereas carriers of the rs13201877 (IFNGR1: 0.65 kg; 95% CI, 0.51-0.79 kg; P = 2.39 × 10-5), rs10733682 (LMX1B: 0.45 kg; 95% CI, 0.27-0.63 kg; P = 6.37 × 10-4), and rs2836754 (ETS2: 0.56 kg; 95% CI, 0.38-0.74 kg; P = 1.51 × 10-4) risk alleles were associated with a greater reduction of body weight after adjustment for age and sex. Conclusions and Relevance: Genes appear to play a minor role in weight reduction by lifestyle in children with overweight or obesity. The findings suggest that environmental, social, and behavioral factors are more important to consider in obesity treatment strategies.

Changing Characteristics of Obese Children and Adolescents Entering Pediatric Lifestyle Intervention Programs in Germany over the Last 11 Years: An Adiposity Patients Registry Multicenter Analysis of 65,453 Children and Adolescents.

OBJECTIVE: To examine whether characteristics of children and adolescents who start lifestyle intervention (LI) for obesity in Germany changed over the last decade. METHODS: 65,453 subjects (<21 years) from the APV database (Adiposity Patients Registry) with a BMI ≥ 90th percentile were included (years 2005-2015). Logistic regression models (confounders: age, sex, migration background) were created for overweight, obesity, extreme obesity, and obesity-related comorbidities. Comorbidities were further adjusted for weight category. Results were stratified by inpatient or outpatient care. RESULTS: Extreme obesity was found to be more frequent at the onset of LI (2005: 11.6; 2015: 12.7%) with a similar trend in subgroups (p < 0.001). Obesity increased (2005: 50.3%; 2015: 55.1%), and overweight decreased (2005: 34.1%; 2015: 29.0%) in the whole study population. Trends were similar for inpatient or outpatient care (all p < 0.001). Hypertension increased from 45.7% to 49.2% in the whole study population, and similar data were obtained in the subgroup of inpatients (both p < 0.0001). Dyslipidemia increased in all patients (2005: 21.9%; 2015: 28.0%) and in inpatients (2005: 20.2%; 2015: 25.7%; both p < 0.0001). Abnormal carbohydrate metabolism rose in all patients (from 5.2 to 6.4%; p = 0.0002) without significant trends in subgroups. CONCLUSION: During the last decade, children and adolescents presented with higher BMI SDS at the onset of LI and the proportion with obesity-related comorbidities increased. Particularly the presence of comorbidities differed between outpatients and inpatients.

Uphill walking: Biomechanical demand on the lower extremities of obese adolescents.

The number of obesity prevalence in adolescents is still increasing. Obesity treatment programs typically include physical activity with walking being recommended as appropriate activity, but limited information exists on the demand uphill walking places on the joint loading and power of obese adolescents. Therefore, the purpose of this study was to investigate the effect of different inclinations on step characteristics, sagittal and frontal joint angles, joint moments and joint power of obese adolescents in comparison to their normal-weight peers. Eleven obese (14.5±1.41 years, BMI: 31.1±3.5kg/m2) and eleven normal-weight adolescents (14.3±1.86 years, BMI: 19.0±1.7kg/m2) walked with 1.11m/s on a ramp with two imbedded force plates (AMTI, 1000Hz) at three inclinations (level, 6°, 12°). Kinematic data were collected via an infrared-camera motion system (Vicon, 250Hz). The two-way (inclination, group) ANOVA indicated a significant effect of inclination on almost all variables analysed, with the hip joint being the most affected by inclination, followed by the knee and ankle joint. The obese participants additionally spent less time in swing phase, walked with an increased knee flexion and valgus angle and an increased peak hip flexion and adduction moment. Hip joint power of obese adolescents was especially in the steepest inclination significantly increased compared to their normal-weight peers. Obese adolescents demonstrate increased joint loading compared to their normal-weight peers and in combination with a musculoskeletal malalignment they might be prone to an increased overuse injury risk.

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults.

BACKGROUND: Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians. METHODOLOGY AND PRINCIPAL FINDINGS: Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2-2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects. CONCLUSIONS AND SIGNIFICANCE: By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.

Health-related quality of life and physical activity in children and adolescents 2 years after an inpatient weight-loss program.

OBJECTIVES: To investigate changes in health-related quality of life (HRQOL), body mass index (BMI), physical activity, and sedentary behavior at 24 months after an inpatient weight-loss program and to examine correlations between changes in HRQOL and BMI or physical activity. STUDY DESIGN: This prospective study included 707 overweight and obese individuals (mean age, 14 ± 2 years; 57% girls) participating in a 4- to 6-week inpatient weight-loss program, 381 of whom completed a 24-month follow-up. HRQOL, physical activity, sedentary behavior, and BMI were assessed at baseline, at discharge, and at 6, 12, and 24 months after starting therapy. Longitudinal analyses were conducted using repeated-measures mixed models, adjusted for age, sex, and baseline outcome and accounting for attrition over time. RESULTS: All variables improved over treatment and 6-month follow-up (P < .05). At 24 months, overall HRQOL indicated improvements relative to baseline (3 points on a scale of 0-100; 95% CI, 1.68-4.47; P < .001). Of the 6 HRQOL domains, the greatest improvement was observed for self-esteem (11 points; 95% CI, 8.40-13.14; P < .001). BMI was 0.5 kg/m(2) lower than at baseline (95% CI, -0.92 to -0.02; P = .04). Long-term changes in physical activity explained 30% of the variation in overall HRQOL (P = .01), and change in BMI was not associated with a change in HRQOL. CONCLUSIONS: This inpatient weight-loss program was associated with positive changes in HRQOL over the long term, with particular improvements in self-esteem. The results indicate the potential role of physical activity in improving HRQOL without a substantial change in body composition.

An inpatient lifestyle-change programme improves heart rate recovery in overweight and obese children and adolescents (LOGIC Trial).

BACKGROUND: Impaired heart rate recovery (HRR) is a strong predictor of overall mortality and cardio-metabolic risk. This study aimed at investigating (1) the effect of participation in a lifestyle-change programme for weight loss on HRR in overweight and obese children and (2) potential associations between the changes in one minute HRR (HRR1) and fitness, weight loss and cardio-metabolic risk. METHODS: The analysis included 429 individuals (169 boys) aged 13.9 ± 2.3 years who participated in an inpatient weight loss programme for four to six weeks. At baseline and the end of the programme clinical investigations were performed, including blood analyses, blood pressure, anthropometry and maximal cycle ergometer exercise testing with continuous heart rate (HR) monitoring. HRR was calculated as the difference between the highest exercising HR and HR at one, three and five minutes post-exercise. RESULTS: Average body weight decreased from 90.7 ± 22.5 kg to 81.9 ± 20.0 kg and peak exercise capacity increased from 1.66 ± 0.38 W/kg to 2.05 ± 0.45 W/kg (p < 0.001). Cardio-metabolic risk factors improved (waist circumference, LDL-cholesterol, HOMA insulin ratio, blood pressure; p < 0.05). HDL-cholesterol and triglyceride levels remained unchanged. Compared with baseline, at follow-up the decline in HR was more pronounced (+32%, +18% and +11% for HRR1, HRR3 and HRR5; p < 0.001). Improvements in HRR1 were weakly correlated with changes in exercise capacity (p < 0.05; r < 0.13), but not with changes in body weight and cardio-metabolic risk factors. CONCLUSIONS: HRR considerably improved after an inpatient weight loss programme in overweight and obese children. This was not associated with improvements in body weight and cardio-metabolic risk; hence HRR would be a valuable addition to cardiovascular risk assessment in this group.

The cardio-metabolic risk of moderate and severe obesity in children and adolescents.

OBJECTIVE: To compare the cardio-metabolic risk profile between moderately obese and severely obese children and adolescents. STUDY DESIGN: Cross-sectional study involving 463 obese 6- to 19-year-olds who were referred to an inpatient weight-loss program. Anthropometric data were assessed and fasting blood samples were analyzed for lipid and glucose metabolism, adipokines, and inflammatory markers. Moderately obese individuals (percentiles corresponding to body mass index ≥ 30 to 35 kg/m(2) at age 18 years) and severely obese individuals (percentiles corresponding to body mass index ≥ 35 kg/m(2) at age 18 years) were defined by sex and age-specific cut-offs according to the International Obesity Task Force. RESULTS: The prevalence of the metabolic syndrome was three times higher in severely obese individuals compared with those who are moderately obese. Mean values for proinsulin, insulin, homeostatic model assessment-insulin resistance, triglycerides, and interleukin-6 were 30%-50% higher in severe obesity compared with moderate obesity. Concentrations of leptin and high-sensitive C-reactive protein were about 1.5-fold higher, adiponectin levels were 12% lower, and resistin levels 10% higher in severely obese individuals compared with moderately obese (all P < .001). CONCLUSION: Severely obese individuals have a markedly more unfavorable cardio-metabolic risk profile than those who are moderately obese. The results of this study underscore the substantial effect of severe obesity on health and highlights that these children need to receive particular attention regarding obesity treatment.

Leptin, adiponectin, and short-term and long-term weight loss after a lifestyle intervention in obese children.

OBJECTIVE: In overweight children, high leptin levels are independently associated with higher risk for cardiovascular disease, whereas adiponectin seems to be protective against type 2 diabetes and atherosclerosis. The study examines the predictive value of leptin for weight loss after a 4- to 6-wk inpatient therapy and again after 1 y; as well as the association among weight loss, leptin, and adiponectin levels and changes in cardiometabolic risk factors after therapy. METHODS: Body mass index (BMI), blood pressure, Tanner stage, and cardiometabolic risk factors were studied in 402 children (59.2% females, 13.9 ± 2.3 y, BMI 33.8 ± 5.7 kg/m(2)) before and after a 4-to 6-wk inpatient intervention (exercise, diet, and behavioral therapy) and BMI 1 y later (n = 206). RESULTS: BMI was reduced from 33.8 ± 5.7 to 30.5 ± 5.1 kg/m(2) (P < 0.001) during the lifestyle intervention and remained unchanged after 1 y. Baseline BMI was positively associated with leptin (r = 0.60; P < 0.001) and cardiometabolic risk factors (blood pressure, high-density lipoprotein [HDL] cholesterol, triglycerides). Baseline leptin was associated with BMI and triglycerides (r = 0.39; P < 0.001), baseline adiponectin with HDL-cholesterol (r = 0.40; P < 0.001). Baseline BMI explained 40.7% of the variance in weight loss during therapy. The combination of BMI, sex, and leptin explained 50.4% of the variance. Neither BMI nor leptin predicted weight changes over the long term. CONCLUSIONS: Overweight children maintained a substantial amount of weight loss after participation in a short-term inpatient lifestyle intervention. Baseline BMI was positively associated with weight reduction during the intervention, whereas baseline leptin had only a minor predictive value.

Long-term effects of an inpatient weight-loss program in obese children and the role of genetic predisposition-rationale and design of the LOGIC-trial.

BACKGROUND: The prevalence of childhood obesity has increased worldwide, which is a serious concern as obesity is associated with many negative immediate and long-term health consequences. Therefore, the treatment of overweight and obesity in children and adolescents is strongly recommended. Inpatient weight-loss programs have shown to be effective particularly regarding short-term weight-loss, whilst little is known both on the long-term effects of this treatment and the determinants of successful weight-loss and subsequent weight maintenance.The purpose of this study is to evaluate the short, middle and long-term effects of an inpatient weight-loss program for children and adolescents and to investigate the likely determinants of weight changes, whereby the primary focus lies on the potential role of differences in polymorphisms of adiposity-relevant genes. METHODS/DESIGN: The study involves overweight and obese children and adolescents aged 6 to 19 years, who participate in an inpatient weight-loss program for 4 to 6 weeks. It started in 2006 and it is planned to include 1,500 participants by 2013. The intervention focuses on diet, physical activity and behavior therapy. Measurements are taken at the start and the end of the intervention and comprise blood analyses (DNA, lipid and glucose metabolism, adipokines and inflammatory markers), anthropometry (body weight, height and waist circumference), blood pressure, pubertal stage, and exercise capacity. Physical activity, dietary habits, quality of life, and family background are assessed by questionnaires. Follow-up assessments are performed 6 months, 1, 2, 5 and 10 years after the intervention: Children will complete the same questionnaires at all time points and visit their general practitioner for examination of anthropometric parameters, blood pressure and assessment of pubertal stage. At the 5 and 10 year follow-ups, blood parameters and exercise capacity will be additionally measured. DISCUSSION: Apart from illustrating the short, middle and long-term effects of an inpatient weight-loss program, this study will contribute to a better understanding of inter-individual differences in the regulation of body weight, taking into account the role of genetic predisposition and lifestyle factors. TRIAL REGISTRATION: NCT01067157.

Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS.

CONTEXT: Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and ß-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents. OBJECTIVE: The aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (± 0.55), mean age: 14 (± 2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy. METHODS: We investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of ß-cell function (HOMA-B), and anthropometric parameters and their change during intervention. RESULTS: The minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205  mmol/l, P<0.0001) and decreased HOMA-B (-0.353, P < 0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger ß-estimates. The P value for the genotype × BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention. CONCLUSIONS: This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories.