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.

MHO is a stable status in childhood obesity as long as pubertal status remains stable. Due to the strong association between puberty and MUO status, the concept of MHO is questionable, at least in pubertal children.

A BMI-SDS reduction of 0.25 or greater significantly improved hypertension, hypertriglyceridemia, and low HDL-cholesterol, whereas a BMI-SDS greater than 0.5 doubled the effect.

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.

Irisin levels are related to pubertal stage and insulin resistance but not to weight status in childhood.

The changes of glutamine, methionine, LPCaC18:1, LPCaC18:2, LPCa20:4, and PCaeC36:2 seem to be related to the changes of dieting or exercise habits in lifestyle intervention or to be a consequence of overweight since they normalized in weight loss. Further studies should substantiate our findings.

In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p < 0.05) at baseline and end and with change during the intervention (p < 0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p < 0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov Identifier NCT00435734.

Objective: The impact of thyroid hormones on weight loss in lifestyle interventions and on weight regain afterwards is unknown. Therefore, we studied the relationships between TSH, free triiodothyronine (fT 3 ), free thyroxine (fT 4 ), and weight status, as well as their changes during and after a lifestyle intervention in obese children. Materials and methods: We evaluated the weight status as BMI-SDS in 477 obese children (mean age 10.6G2.7 years, 46% male, mean BMI 28.1G4.5 kg/m 2 ) participating in a 1-year lifestyle intervention in a 2-year longitudinal study. Changes in BMI-SDS at 1 and 2 years were correlated with TSH, fT 3 , and fT 4 concentrations at baseline and their changes during the intervention. Results: A decrease in BMI-SDS during the intervention period (K0.32G0.38; P!0.001) was significantly positively associated with baseline TSH and fT 3 in multiple linear regression analyses adjusted for age, sex, pubertal stage, and baseline BMI-SDS. An increase in BMI-SDS after the end of the intervention (C0.05G0.36; PZ0.011) was significantly related to the decreases in TSH and fT 3 during the intervention in multiple linear regression analyses adjusted for change in BMI-SDS during the intervention. In contrast to children with weight maintenance, children with weight regain after the end of the intervention demonstrated a decrease in their TSH levels (K0.1G1.6 vs C0.2G 1.6 mU/l; PZ0.03) and fT 3 (K0.2G1.1 vs C0.3G1.6 pg/ml; P!0.001) during the intervention. Conclusions: The decreases in TSH and fT 3 concentrations during the lifestyle intervention were associated with weight regain after the intervention. Future studies should confirm that the decreases in TSH and fT 3 levels associated with weight loss are related to the change in metabolism such as resting energy expenditure.