Objective: The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity. Methods: Serum samples of 80 obese and 40 normal-weight children between 6 and 15 years of age were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Metabolite concentrations and metabolite ratios were compared between obese and normal-weight children as well as between children of different pubertal stages. Results: Metabolite concentration profiles of obese children could be distinguished from those of normal-weight children. After correction for multiple testing, we observed 14 metabolites (glutamine, methionine, proline, nine phospholipids, and two acylcarnitines, p < 3.8 × 10^–4) and 69 metabolite ratios (p < 6.0 × 10^–6) to be significantly altered in obese children. The identified metabolite markers are indicative of oxidative stress and of changes in sphingomyelin metabolism, in β-oxidation, and in pathways associated with energy expenditure. In contrast, pubertal stage was not associated with metabolite concentration differences. Conclusion: Our study shows that childhood obesity influences the composition of the serum metabolome. If replicated in larger studies, the altered metabolites might be considered as potential biomarkers in the generation of new hypotheses on the biological mechanisms behind obesity.

Younger age was associated with the best long-term outcome after participation in the lifestyle intervention, which supports the need for early intervention in childhood obesity. Children aged 8-10 y may need modified intervention, because BMI-SDS increased more in the older children in the long term. However, mean BMI-SDS was significantly lower 4 y after the end of the intervention than at baseline in all age groups. This study was registered at clinicaltrials.gov as NCT00435734.

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Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.

Objective: Small for gestational age (SGA) children are at risk of both later obesity and metabolic syndrome (MetS). However, it is unknown whether obesity or SGA status leads to MetS in these subjects. We hypothesized that overweight children with former SGA status had more present components of the MetS than overweight children with former appropriate for gestational age (AGA) status. Methods: We analyzed 803 overweight children (4% SGA, mean age 11G0.1 years, body mass index (BMI) 27.3G0.2, SDS-BMI 2.32G0.02) concerning blood pressure, lipids, glucose, and insulin. Oral glucose tolerance tests (oGTT) were performed in all 35 former SGA children and 147 randomly chosen former non-SGA children. Results: After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was significantly related to blood pressure, triglyceride, insulin, and 2 h glucose levels in oGTT. The MetS prevalence was more than doubled in overweight former SGA subjects (40% MetS) compared with overweight former AGA subjects (17% MetS). The corresponding adjusted odds ratio was 4.08 (95% confidence interval 1.48 to 11.22) for SGA compared with AGA children. Conclusions: Overweight former SGA children had an increased risk for the components of the MetS compared with overweight former AGA children. Therefore, SGA status seems to be a risk factor for the MetS independently of weight status. Particularly overweight children with former SGA status should be screened for the MetS.

The main risk factors for prediabetes were parental diabetes, pubertal stage, and extreme obesity. Screening for prediabetes seems meaningful in subjects with either a parental history of diabetes or a combination of extreme obesity and pubertal stage and detected nearly 90% of the overweight children and adolescents with prediabetes.

Objective:The relationships between obesity, pubertal development, and height are controversial. Therefore, we compared the prevalence of pubarche, menarche, and voice break between a large collective of obese and normal-weight children and adolescents aged 10 -16 years. Methods: We assessed weight, height, pubarche, menarche, and voice break in 1383 obese German children and in 6615 children of a representative national German cohort aged 10 -16 years. In all obese children, gonadotropins were determined and birth weight data were collected. Results : Independently of gender, the height standard deviation score (SDS) was signifi cantly greater (0.3 -1.0) in obese children < 14 years compared to the reference cohort. Independently of age, the percentage of obese boys with pubarche was signifi cantly lower compared to age-matched normal-weight boys. In girls < 13 years, the prevalence of obese girls with pubarche was signifi cantly lower compared to age-matched normal-weight girls. In boys ≥ 11 years, the percentage of obese boys with change of voice was signifi cantly lower compared to age-matched normal-weight boys. In girls ≥ 11 years, the prevalence of obese girls with menarche was signifi cantly lower compared to age-matched normal-weight girls. Birth weight had no impact on pubarche in the obese children. Luteinizing hormone was > 0.3 IU/L in 86 % of the children ≥ 10 years with pubarche. Conclusions : Obese children are taller than normal-weight children up to the age of 14 years. Since obese children demonstrated pubarche, menarche, and voice break later than their normal-weight peers, the increase in height in obese children does not seem to be attributable to earlier onset of puberty.

GeneticsRecent genome-wide association studies (GWAS) conducted in population-based samples assessed for BMI or in case-control samples assessed for extreme obesity led to the discovery of genetic loci relevant for body-weight regulation (reviewed in ref. 1). Taken together variants at 32 loci have been reported to be associated to BMI (ref. 2, n = 249,796). In addition, Meyre et al. (3) reported five loci to be relevant for extreme obesity (n = 16,982). Common to all these studies is their relative focus on adults.Focusing on children and adolescents, a GWAS meta-analysis (ref. 4; n = 2,258) confirmed three known loci for obesity (FTO, MC4R, and TMEM18) and provided evidence for two new loci (SDCCAG8 and TNKS/MSRA) with the latter finding being limited to children and adolescents. A total of 36,468 individuals (8,092 children and adolescents) were genotyped for the confirmation.Here, we explore the effect of 10 single-nucleotide polymorphisms (SNPs) representative of the five loci on measures of weight loss and cardiometabolic risk profile change after a lifestyle intervention for obese humans. We analyzed the SNPs in 401 overweight children and adolescents completing a 1-year lifestyle intervention. In addition, we investigated the SNPs which were significantly associated with weight loss in an independent sample of 626 adults who completed a 10-week intervention with a focus on a hypoenergetic diet (NUGENOB).Baseline characteristics and their changes of the overweight children and adolescents who completed the "Obeldicks" intervention are shown in Table 1. Associations of the 10 analyzed "obesity-SNPs" to weight loss-related effects are shown in Table 2. Genotype-dependent effects on overweight reduction as measured by BMI-standard deviation score (SDS) changes were Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m 2 , mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10 −6). However, our results could not be confirmed i...