Effect of Weight Loss on Puberty Onset in Overweight Children.

OBJECTIVE: To assess the impact of weight changes on the onset of puberty in overweight children. STUDY DESIGN: We evaluated the timing of puberty onset in 160 prepubertal overweight children (aged 11.2 ± 1.0 years) depending on the changes of their weight status in a 1-year lifestyle intervention. We determined body mass index (BMI), pubertal stage, luteinizing hormone (LH), follicle-stimulating hormone, insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein-3, insulin resistance index homeostatic model assessment, and serum gonadotropins at baseline and 1 year later. RESULTS: Puberty onset during the 1-year follow-up was significantly (P = .014) more frequent in girls without BMI-SDS reduction (75.0%) compared with girls with BMI-SDS reduction (45.7%). The start of puberty was significantly (P = .024) more frequent in boys with BMI-SDS reduction (76.9%) compared with boys without BMI-SDS reduction (53.6%). In logistic regression analyses adjusted for baseline age and BMI-SDS, BMI-SDS reduction was associated with a decreased likelihood for puberty onset in girls (OR 0.24; 95% CI 0.07-0.85) and an increased likelihood in boys (OR 3.77; 95% CI 1.34-10.52). Central onset of puberty was confirmed by an increase of LH concentration and LH/follicle-stimulating hormone ratio in both boys and girls. Homeostatic model assessment, IGF-1, and IGF-1/insulin-like growth factor binding protein-3 ratio as marker for free IGF-1 at baseline or their changes were not associated with the onset of puberty. CONCLUSIONS: BMI-SDS reduction in overweight children was associated with earlier gonadotropin-dependent onset of puberty in boys and later onset of puberty in girls, suggesting earlier puberty in obese girls and later puberty in obese boys. We found no evidence that insulin resistance or IGF-1 have an impact on the start of puberty in obese children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00435734.

Weight loss in obese girls with polycystic ovarian syndrome is associated with a decrease in Anti-Muellerian Hormone concentrations.

OBJECTIVE: The Anti-Muellerian Hormone (AMH) has been reported as surrogate marker of antral follicles, which are the origins of hyperandrogenism in polycystic ovarian syndrome (PCOS). Therefore, AMH may be useful for the diagnosis of PCOS. The objective was to study the longitudinal changes in AMH concentrations in girls with and without PCOS. DESIGN: This is a longitudinal study of obese girls participating in a 1-year lifestyle intervention. PATIENTS: Forty obese girls aged 13-16 years (50% with PCOS) were included in the study. Girls with and without PCOS were matched to age, BMI and change in weight status. MEASUREMENTS: AMH, gonadotropins, androstenedione, testosterone, oestradiol and sex hormone-binding globulin (SHBG) were determined. RESULTS: Obese girls with PCOS demonstrated significantly (P<.001) higher AMH concentrations (5.8±3.1 ng/mL) compared to obese girls without PCOS (2.4±1.4 ng/mL). None of the girls without PCOS had AMH concentrations ≥6 ng/mL and none of the PCOS girls showed AMH concentrations ≤3 ng/mL. Weight loss in girls with PCOS was associated with a significant drop in AMH concentrations (-1.4±1.8 ng/mL, P=.045). AMH was significantly related to testosterone (cross-sectional: b-coefficient 3.7±1.7, P=.001, longitudinal: b-coefficient 0.54±0.47, P=.026) and luteinizing hormone (LH) (cross-sectional: b-coefficient 0.05±0.04, P=.039, longitudinal: b-coefficient 0.005±0.004, P=.039), but not to any other analysed parameter in multiple linear regression analyses adjusted to multiple confounders. CONCLUSIONS: AMH was increased in adolescent girls with PCOS and normalized with weight loss. AMH was cross-sectionally and longitudinally related to hyperandrogenism.

Changes in the serum metabolite profile in obese children with weight loss.

PURPOSE: Childhood obesity is an increasing problem and is accompanied by metabolic disturbances. Recently, we have identified 14 serum metabolites by a metabolomics approach (FIA-MS/MS), which showed altered concentrations in obese children as compared to normal-weight children. Obese children demonstrated higher concentrations of two acylcarnitines and lower levels of three amino acids, six acyl-alkyl phosphatidylcholines, and three lysophosphatidylcholines. The aim of this study was to analyze whether these alterations normalize in weight loss. METHODS: We analyzed the changes of these 14 metabolites by the same metabolic kit as in our previous study in serum samples of 80 obese children with substantial weight loss (BMI-SDS reduction >0.5) and in 80 obese children with stable weight status all participating in a 1-year lifestyle intervention. RESULTS: In the children without weight change, no significant changes of metabolite concentrations could be observed. In children with substantial weight loss, glutamine, methionine, the lysophosphatidylcholines LPCaC18:1, LPCaC18:2, and LPCa20:4, as well as the acyl-alkyl phosphatidylcholine PCaeC36:2 increased significantly, while the acylcarnitines C12:1 and C16:1, proline, PCaeC34:1, PCaeC34:2, PCaeC34:3, PCaeC36:3, and PCaeC38:2 did not change significantly. CONCLUSIONS: 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.

Carotid Intima-Media Thickness in Children Treated with Growth Hormone: A Follow-Up Study over Three Years.

BACKGROUND: There is an ongoing discussion whether high doses of growth hormone (GH) may lead to cardiovascular diseases. Therefore, we studied the longitudinal relationships between GH treatment and carotid intima-media thickness (cIMT), which is predictive of the development of atherosclerosis. METHODS: We measured blood pressure, lipids, hemoglobin HbA1c, IGF-1, IGFBP-3, and cIMT in 28 children treated with supraphysiological doses of GH (mean age 9.8 ± 2.2 years, 39% males) and 36 children suffering from GH deficiency (GHD) and treated with physiological doses of GH (mean age 9.7 ± 2.2 years, 72% males) in a longitudinal study over 3 years. RESULTS: The cIMT values did not change significantly in the observation period in children with GHD (Δmaximum and Δmean cIMT 0.0 ± 0.1 mm). The mean (+0.1 ± 0.1 mm) but not the maximum cIMT (0.0 ± 0.1 mm) increased significantly (p = 0.049) in the children treated with supraphysiological doses of GH. Blood pressure, lipids, and HbA1c were not related to cIMT, while IGF-1, IGFBP-3, body mass index expressed as a standard deviation score, and treatment duration correlated significantly with cIMT. CONCLUSIONS: We did not find any robust evidence that GH treatment is associated with changes in cIMT. Further studies are necessary to analyze the impact of IGF-1 and IGFBP-3 concentrations on cIMT.

Carotid intima-media thickness in children treated with growth hormone.

BACKGROUND: There is an ongoing discussion whether high doses of growth hormone (GH) may lead to cardiovascular diseases. Therefore, we studied the relationships between GH treatment and carotid intima-media thickness (cIMT), which is predictive of the development of atherosclerosis. METHODS: We measured cIMT in 38 children with supraphysiological doses of GH (mean age 10.9 ± 2.2 years; 47% male; GH indication: small for gestational age, n = 31; Turner syndrome, n = 5; SHOX deficiency, n = 2) and in 38 age- and gender-matched healthy children without GH treatment. Furthermore, we examined cIMT in 61 children with physiological doses of GH (mean age 12.0 ± 3.1 years; 64% male; GH indication: GH deficiency) and in 61 age- and gender-matched healthy children without GH treatment. Moreover, we analyzed blood pressure, lipids, HbA1c, IGF-1, and IGFBP-3 in children treated with GH. RESULTS: The cIMT levels did not differ significantly between children with and without GH treatment either in high-dose GH treatment or in physiological GH doses. In backwards linear regression analyses, cIMT was significantly related to HbA1c, but not to age, gender, BMI, pubertal stage, indication of GH treatment, duration or doses of GH treatment, IGF-1, IGFBP-3, or to any cardiovascular risk factor. CONCLUSIONS: We found no evidence that GH treatment is associated with changes in cIMT.

Strong effect of pubertal status on metabolic health in obese children: a longitudinal study.

CONTEXT: The concept of metabolic healthy obese (MHO) status has been proposed also for children. However, it is unclear whether this is a stable status in childhood. OBJECTIVE: The aim was to analyze the changes of MHO status over time. DESIGN AND SETTING: This is 1-year longitudinal analysis of our obesity cohort. PARTICIPANTS: All obese children of our outpatient obesity clinic with 1-year follow-up were included. INTERVENTIONS: Standard care intervention was used. MAIN OUTCOME MEASURES: We examined body mass index (BMI), waist circumference, pubertal stage, blood pressure, fasting lipids, glucose, and insulin resistance index homeostasis model assessment (HOMA). MHO status was defined by absence of cardiovascular risk factors. RESULTS: A total of 2017 obese children (mean age, 11.6 ± 2.8 y; 45% male; BMI, 28.5 ± 5.3 kg/m(2); BMI-z score, 2.4 ±0.5) were enrolled onto the study, and 49.3% of the children were MHO at baseline. After 1 year, the majority of the MHO remained MHO (68.0%). MHO children were significantly younger, more frequently prepubertal, and less overweight compared with metabolic unhealthy obese (MUO) children (all P < .05). In the longitudinal analyses, entering into puberty (OR, 1.9; 95% confidence interval, 1.3-2.8]; P = .004) doubled the risk for switching from MHO to MUO, whereas changing from mid to late puberty nearly tripled the likelihood for switching from MUO to MHO (OR 3.1 [2.1-4.5], P < .001) in multiple logistic regression analyses adjusted for age, sex, and changes of body mass index standard deviation score (BMI-SDS). CONCLUSIONS: 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.

Components of the metabolic syndrome are negative predictors of weight loss in obese children with lifestyle intervention.

BACKGROUND AND AIMS: Insulin resistance has been proposed to be associated with weight gain in obesity. Therefore, we analyzed the impact of insulin resistance and its associated cardiovascular risk factors (CRFs) summarized in the Metabolic Syndrome (MetS) on change of weight status in obese children. METHODS: We analyzed 484 obese children who had participated in a lifestyle intervention and 533 obese children without lifestyle intervention. The changes of BMI-SDS in the time period of 1-year were related to baseline fasting insulin resistance index HOMA, blood pressure, waist circumference, waist-to-height ratio, lipids, uric acid, and HbA1c. RESULTS: In contrast to obese children without lifestyle intervention, BMI-SDS decreased and the majority of CRFs improved significantly in obese children with lifestyle intervention. Age, BMI, waist circumference, waist-to-height ratio, blood pressure, uric acid, triglycerides, and HOMA were negatively significantly related to reduction of BMI-SDS in children with lifestyle intervention. In multiple linear regression analysis adjusted for gender, pubertal stage, and treatment center (R² = 0.26), waist circumference (r = -0.016 [confidence interval -0.019 up to -0.013], p < 0.001) was the strongest negative predictor of weight loss in children with lifestyle intervention. In children without lifestyle intervention, we did not find significant relationships between change of BMI-SDS and CRFs including insulin resistance in multiple regression analysis. CONCLUSIONS: Insulin resistance and components of the MetS were associated negatively with weight loss in lifestyle intervention. Waist circumference at baseline was the strongest negative predictor of weight loss suggesting that obese children with abdominal fat distribution need more intensive interventions. This study is registered at clinicaltrials.gov (NCT00435734).

Relationships between 24-hour urinary free cortisol concentrations and metabolic syndrome in obese children.

CONTEXT: Clinical features of Metabolic Syndrome (MetS) and Cushing's Syndrome are similar, suggesting a pathogenetic role of hypothalamus-pituitary-adrenal axis in MetS. OBJECTIVE: The aim of the study was to determine whether MetS diagnosis and specific clusters of MetS components (waist circumference, dyslipidemia, hypertension, and impaired glucose metabolism) are associated with serum cortisol (SC) or 24-h urinary free cortisol (UFC) levels. DESIGN AND SETTING: We conducted cross-sectional analyses of data from our obesity cohort. We studied 264 obese children (age, 11.0 ± 2.8 years; male, 48%; BMI, 28.2 ± 5.4 kg/m(2)). We examined UFC, SC, homeostasis model assessment (HOMA), and features of MetS (waist circumference, blood pressure, fasting lipids, and glucose). RESULTS: Slightly increased UFC concentrations were measured in 30.7% of the children. Obese children with MetS had significantly (P = .003) higher UFC levels compared with obese children without MetS. Girls demonstrated significantly higher UFC concentrations compared with boys independent of pubertal stage. UFC and SC levels were significantly related to features of MetS, but the associations were stronger for UFC. In multivariate analyses adjusted for age, sex, and body mass index, none of the features of MetS but HOMA index was correlated with UFC, whereas SC demonstrated no significant association to any parameter of MetS or HOMA. CONCLUSIONS: Our findings support the hypothesis that changes in the hypothalamus-pituitary-adrenal axis are related to MetS in obesity. UFC seems to be a suitable marker for this relationship. Norm values for UFC adapted to obese children may help to avoid unnecessary dexamethasone suppression tests.