Coenzyme Q10 concentration in plasma and blood cells of juvenile patients hospitalized for anorexia nervosa.

The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 °C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients.

The impact of insulin resistance and hyperandrogenemia on polysomnographic variables in obese adolescents with polycystic ovarian syndrome.

PURPOSE: We aimed to determine the impact of insulin resistance and hyperandrogenemia on polysomnographic variables in obese adolescents with polycystic ovarian syndrome (PCOS), as studies in adults with PCOS suggest that parameters of glucose metabolism and serum androgens are related to respiratory polysomnographic variables (RPV), and the symptoms of PCOS usually begin around menarche. METHODS: We divided our study group of obese adolescents with PCOS according to HOMA-index and in a second analysis according to free androgen index (FAI). Study group A consisted of 14 girls with HOMA-index <4, study group B of 17 girls with HOMA-index >4. Study group C consisted of 19 girls with FAI <10, and study group D of 18 girls with FAI >10. The control group for both analyses consisted of 19 healthy obese adolescents without PCOS. All girls underwent overnight 12-channel polysomnography. RESULTS: In both analyses, we found no differences between the groups concerning the RPV. Study group B demonstrated a significantly lower percentage of REM-sleep than the control group (p = 0.02). Study group D demonstrated a significantly lower percentage sleep stages 3 and 4 of non-REM-sleep than study group C and the controls (p = 0.008). Study group D demonstrated significantly lower sleep efficiency than the controls (p = 0.03). CONCLUSIONS: Insulin resistance and hyperandrogenemia do not seem to have a significant impact on RPV in obese adolescents with PCOS. Differences in sleep architecture found between patients with PCOS and controls, however, are possibly influenced by insulin resistance and/or serum androgens.

Longitudinal analyses of polysomnographic variables, serum androgens, and parameters of glucose metabolism in obese adolescents with polycystic ovarian syndrome.

PURPOSE: The prevalence of obstructive sleep apnea syndrome (OSAS) is clearly increased in adults with polycystic ovarian syndrome (PCOS), whereas OSAS does not seem to be frequent in adolescents with PCOS, pointing towards the fact that some patients with PCOS develop OSAS in the further course of the disease. We therefore aimed to analyze the changes of polysomnographic variables in obese adolescents with PCOS in a longitudinal analysis. METHODS: Fifteen adolescents with PCOS (age 15.3 years ± 1.2, BMI 32.9 kg/m(2) ± 6.4, SDS-BMI 2.5 ± 0.8) underwent overnight 12-channel polysomnography at baseline and after a mean duration of 28 ± 6 months (age 17.8 years ± 1.1, BMI 32.7 kg/m(2) ± 7.0, SDS-BMI 2.1 ± 0.9). After performing the initial polysomnography, we treated hyperandrogenemia and insulin resistance in the study group. We determined parameters of body weight/body composition, parameters of glucose metabolism, and serum androgens in all patients at baseline and follow-up. At follow-up, we compared the polysomnographic variables of the study group to those of healthy female adults. RESULTS: The polysomnographic variables, the parameters of body weight/body composition, and the parameters of glucose metabolism in the study group did not change significantly during the observation period. The serum levels of total testosterone and sex hormone binding globulin increased significantly, whereas free androgen index decreased significantly. At follow-up, the polysomnographic variables of the study group did not differ from those of healthy female adults. CONCLUSIONS: OSAS does not seem to develop in adolescents with PCOS being treated for hyperandrogenism and insulin resistance. The pathogenesis of OSAS in PCOS needs to be examined in larger controlled studies.

A comparison of polysomnographic variables between adolescents with polycystic ovarian syndrome with and without the metabolic syndrome.

BACKGROUND: We aimed to determine the differences in polysomnographic variables between obese adolescents with polycystic ovarian syndrome (PCOS) with and without metabolic syndrome, as the prevalence of obstructive sleep apnea syndrome (OSAS) is increased in adults with PCOS, OSAS has been regarded as a manifestation of the metabolic syndrome, and the prevalence of metabolic syndrome is increased in patients with PCOS. METHODS: Fourteen obese adolescents with PCOS and metabolic syndrome [15.7 years ± 1.9, body mass index (BMI) 36.2 kg/m(2) ± 6.2], 14 obese adolescents with PCOS without metabolic syndrome (15.7 years ± 1.1, BMI 33.8 kg/m(2) ± 6.2), 19 healthy, obese adolescents without PCOS or metabolic syndrome (15.3 years ± 1.0, BMI 34.4 kg/m(2) ± 6.5), and 14 healthy, normal-weight adolescents (15.4 years ± 0.7, BMI 21.1 kg/m(2) ± 2.2) underwent polysomnography to compare transcutaneous arterial oxygen saturation (Sat O(2)), apnea index (AI), hypopnea index (HI), apnea-hypopnea index (AHI), the absolute number of obstructive apneas (NOA), percentage sleep stages 3 and 4 of non REM-sleep (stages 3 and 4), percentage of rapid eye movement (REM) sleep (%REM), sleep-onset latency, and sleep efficiency. RESULTS: We found no differences among the four groups concerning AI, HI, AHI, NOA, and stages 3 and 4. Significant differences among the groups were found regarding Sat O(2) (P = 0.04), %REM (P = 0.03), sleep-onset latency (P = 0.002), and sleep efficiency (P = 0.01). CONCLUSIONS: Weight status, PCOS, and metabolic syndrome do not seem to have significant effects on respiratory polysomnographic variables in adolescent girls with PCOS, suggesting that the pathomechanisms leading to OSAS in patients with PCOS develop in the later course of the disease.

Relationships between polysomnographic variables, parameters of glucose metabolism, and serum androgens in obese adolescents with polycystic ovarian syndrome.

The aim of this study was to compare polysomnographic variables of obese adolescents with polycystic ovarian syndrome (PCOS) to those of healthy controls and to analyse whether polysomnographic variables correlate to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. Thirty-one obese adolescents with PCOS (15.0 years ± 1.0, body mass index 32.7 kg per m(2) ± 6.2) and 19 healthy obese adolescents without PCOS (15.2 years ± 1.1, body mass index 32.4 kg per m(2) ± 4.0) underwent polysomnography to compare apnoea index, hypopnoea index, apnoea-hypopnoea index, the absolute number of obstructive apnoeas, percentage sleep Stages 1, 2, 3 and 4 of non-rapid eye movement (NREM) sleep, percentage of REM sleep, TIB, total sleep time (TST), sleep-onset latency, total wake time (TWT), wakefulness after sleep onset (WASO) and sleep efficiency. Furthermore, we correlated polysomnographic variables to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. We found no differences between the two groups concerning the respiratory indices, percentage sleep Stages 2, 3 and 4 of NREM sleep, TIB and sleep-onset latency. The girls with PCOS differed significantly from the controls regarding TST, WASO, TWT, sleep efficiency, percentage Stage 1 of NREM sleep and percentage of REM sleep. We found a weak significant correlation between insulin resistance and apnoea index and between insulin resistance and apnoea-hypopnoea index. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.

A comparison of polysomnographic variables between obese adolescents with polycystic ovarian syndrome and healthy, normal-weight and obese adolescents.

PURPOSE: The purpose of this study was to determine the differences in polysomnographic variables between obese adolescents with polycystic ovarian syndrome (PCOS) and healthy, normal-weight and obese controls, as the prevalence of obstructive sleep apnea syndrome (OSAS) is increased in adults with PCOS. METHODS: Twenty-two obese adolescents with PCOS (mean age 15.2 +/- 1.3 years, mean BMI 31.7 +/- 6.2 kg/m(2)), 18 healthy, normal-weight adolescents (mean age 15.0 +/- 0.9 years, mean BMI 20.6 +/- 2.3 kg/m(2)), and 11 healthy, obese adolescents (mean age 15.0 +/- 1.0 years, mean BMI 34.8 +/- 8.7 kg/m(2)) underwent polysomnography to compare mean transcutaneous arterial oxygen saturation (Sat O(2)), apnea index (AI), hypopnea index (HI), apnea-hypopnea index (AHI), the absolute number of obstructive apneas (NOA), percentage sleep stages 3 and 4 of non-REM sleep (stages 3 and 4), percentage of REM sleep (%REM), sleep-onset latency, and sleep efficiency. RESULTS: We found no differences between the three groups concerning Sat O(2), AI, HI, AHI, NOA, and stages 3 and 4. The girls with PCOS differed from normal-weight and obese controls regarding sleep-onset latency and sleep efficiency and from the normal-weight controls regarding %REM. CONCLUSIONS: OSAS does not seem to be more prevalent in adolescents with PCOS. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.

Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention.

OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the "Obeldicks" lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention "Obeldicks". The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and growth in obese children before and after reduction of overweight.

UNLABELLED: Little longitudinal information is available on changes of growth, insulin-like growth factor-I (IGF-I), its main binding protein (IGFBP-3) and their relationships to leptin and insulin in obese children reducing their overweight. We compared these parameters between baseline and after participating in a one-year lifestyle intervention in 319 obese children. The control group comprised 52 lean children. Obese children demonstrated significantly increased IGFBP-3, leptin, and insulin concentrations and were taller compared to the lean children, while they did not differ in respect to their IGF-I concentrations. Reduction of overweight was associated with a significant decrease of IGFBP-3 SDS, leptin, and insulin concentrations. IGF-I SDS and height SDS did not change after weight loss. CONCLUSIONS: IGFBP-3, leptin and insulin concentrations are increased in obese children and normalized in weight loss demonstrating the reversibility of these alterations. Weight loss due to lifestyle intervention was not associated with growth disturbances.

Association between leptin and transaminases: 1-year follow-up study in 180 overweight children.

Leptin and insulin resistance are being discussed to be involved in the pathogenesis of nonalcoholic fatty liver disease, which is frequently characterized by moderately elevated transaminases. However, longitudinal studies proving an association between leptin, insulin resistance, and transaminases are scarce. We examined weight status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), leptin, glucose, and insulin in 180 overweight children at baseline and 1 year later. Relationships between these parameters at baseline and their changes in the course of 1 year were determined by multiple regression analysis adjusted for age, sex, pubertal stage, and body mass index (BMI). Leptin but not homeostasis model assessment of insulin resistance index correlated significantly to transaminases in both cross-sectional and longitudinal analyses. The same findings were observed in 30 children with suspected nonalcoholic fatty liver disease by ultrasound. The 130 children who participated in a 1-year lifestyle intervention reduced their overweight (standard deviation score [SDS]-BMI, -0.37 +/- 0.11). In the course of 1 year, their changes of transaminases depended on change of weight status (SDS-BMI decrease >0.5: ALT 12 [10-15] --> 9 [8-13] U/L, AST 11 [9-12] --> 9 [8-12] U/L; SDS-BMI decrease >0 but 16 [12-26] U/L, AST 10 [8-14] --> 10 [8-24] U/L; no SDS-BMI decrease: ALT 13 [11-20] --> 20[13-33] U/L, AST 11 [9-21] --> 15 [9-24] U/L; data as median and interquartile range). The 50 children without intervention increased their SDS-BMI (+0.02 +/- 0.18) and transaminases (ALT 14 [11-18] --> 19 [15-25] U/L, AST 10 [8-15] --> 16 [10-25] U/L). These findings suggest that leptin may be involved in the pathogenesis of liver diseases. However, to test this hypothesis, careful histologic assessments in correlation to leptin levels are needed.

Plasma and thrombocyte levels of coenzyme Q10 in children with Smith-Lemli-Opitz syndrome (SLOS) and the influence of HMG-CoA reductase inhibitors.

INTRODUCTION: SLOS is caused by a defect of cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to improve biochemical parameters in this condition, but they have also been associated with CoQ10 deficiency in patients with hypercholesterolemia. The aim of this study was to analyse plasma and intracellular CoQ10 levels in SLOS patients and to determine the influence of HMG-CoA reductase inhibitors. METHODS: Plasma concentrations of CoQ10 and vitamin E were measured in 14 patients, intracellular CoQ10 levels were determined in platelets of 10 patients with SLOS and compared to controls. RESULTS: Plasma CoQ10 and vitamin E levels were significantly lower in SLOS patients. This difference equalised after adjustment to cholesterol concentrations. Treatment with simvastatin did not influence CoQ10 levels and redox status. Platelet CoQ10 concentrations were similar between patients and controls but there were striking differences in the CoQ10 redox status with a decrease of oxidised CoQ10. CONCLUSION: Decreased concentrations of plasma CoQ10 and vitamin E in SLOS patients are due to a diminished carrier capacity. The higher percentage of reduced CoQ10 in platelets points to an up-regulation of mitochondrial protection mechanisms. Further studies are needed to evaluate a possible benefit of CoQ10 supplementation in SLOS patients.

Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with diabetes mellitus type 1.

Hyperglycaemia has been reported to cause increased production of oxygen free radicals. Oxidative stress may contribute to the pathogenesis of diabetic complications. Coenzyme Q(10) (CoQ(10)) is known for its key role in mitochondrial bioenergetics and is considered as a potent antioxidant and free radical scavenger. This study was conducted to evaluate plasma and blood cell concentrations of CoQ(10) in accordance to its redox capacity in children with diabetes mellitus type 1. CoQ(10) plasma and blood cell concentrations and redox status were measured using high-performance liquid chromatography with electrochemical detection in 43 children with diabetes mellitus type 1 and compared with 39 healthy children. In addition, the diabetic patients were subdivided according to their haemoglobin A1c (HbA1c) values into two groups, that is, those with good control (<8%) and those with poor control (>8%), and the CoQ(10) status was compared between the two groups. Children with type 1 diabetes showed increased plasma levels of CoQ(10) in comparison to healthy children. While CoQ(10) erythrocyte and platelet concentrations did not differ, in the diabetes group, the platelet redox status differed with a significantly increased part of reduced CoQ(10). This difference in concentration and redox status in comparison to healthy controls may be attributed to the subgroup of patients with poor control, as the subdivision of diabetic patients according to their HbA1c values shows. In diabetic children, especially in those with poor control, an increase in plasma concentration and intracellular redox capacity of the antioxidant CoQ(10) may contribute to the body's self-protection during a state of enhanced oxidative stress.

Thyroid hormones and their relation to weight status.

BACKGROUND/AIMS: The aim of this study was to analyze thyroid hormones in female adolescents with obesity and anorexia nervosa (AN) before and after normalization of weight. METHODS: Thyroid-stimulating hormone (TSH), fT3, and fT4 were determined in 100 obese girls, 32 normal-weight girls and 20 girls with AN aged 14-18 years at baseline and 1 year later. Additionally, leptin, insulin, and the insulin resistance index HOMA were analyzed in the obese and normal-weight girls. RESULTS: TSH and fT3 levels of girls with AN were significantly lower compared to TSH concentrations of normal-weight girls, while TSH and fT3 levels of the obese girls were significantly higher. The 21 obese females with weight loss >5% demonstrated a significant decrease in fT3 and TSH, while the 9 adolescents with AN and weight gain >5% showed a significant increase in fT3 and TSH. Insulin and HOMA were not significantly correlated to TSH, fT3 and fT4, while leptin was correlated to TSH and fT3 in both cross-sectional and longitudinal analysis. CONCLUSIONS: Thyroid function seems to be reversibly related to weight status with increased TSH and fT3 concentrations in obesity and decreased TSH and fT3 levels in AN. We hypothesize that leptin may be the link between weight status and TSH.

Precocious pseudopuberty due to autonomous ovarian cysts: a report of ten cases and long-term follow-up.

We report the findings and clinical course of ten girls aged 0.2 to 6.3 years with precocious pseudopuberty due to autonomous ovarian cysts. We found elevated oestrogen levels in five patients and failure of gonadotropin response to GnRH stimulation in four patients during the first episode, of the disease. In one patient, a GnRH stimulation test was not performed. Pelvic ultrasound examination showed large ovarian cysts in all ten patients. Following the initial episode the secondary sexual characteristics of nine patients regressed completely without treatment. The cyst of one girl was removed surgically on demand of her parents. Three girls presented recurrent autonomous ovarian cysts. Two of these girls developed central precocious puberty requiring treatment with a GnRH-agonist after repeated episodes of precocious pseudopuberty. We started treating the third girl with a GnRH agonist after the second relapse of the autonomous ovarian cyst because of rapidly advancing bone age. We conclude that in the majority of cases autonomous ovarian cysts regress spontaneously and that surgery is in general not indicated. Furthermore, autonomous ovarian cysts can relapse before the onset of physiological puberty and accelerate biological maturation leading to central precocious puberty and consequent decrease of height potential.

Coenzyme Q10 concentration in the plasma of children suffering from acute lymphoblastic leukaemia before and during induction treatment.

Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant. This property combined with its essential function in mitochondrial energy production suggests that it may have therapeutic potential in cancer treatment. As part of the body's antioxidant defence against free radical production, CoQ10 concentrations may change during anti-cancer chemotherapy. Our study measured CoQ10 concentration in the plasma of 27 children with acute lymphoblastic leukaemia (ALL) at the time of diagnosis, during induction (protocol ALL-BFM 2000), and post induction treatment. The starting values were compared to the CoQ10 concentrations in 92 healthy children. The total CoQ10 concentration and its redox status were measured by HPLC using electrochemical detection and internal standardisation. While the CoQ10 concentration in the plasma of children with ALL was within a normal range at the time of diagnosis (0.99 +/- 0.41 pmol/microl), a drastic increase was observed during induction treatment (2.19 +/- 1.01 pmol/mul on day 33). This increase was accompanied by shift in the redox status in favour of the reduced form of CoQ10. The increase in CoQ10 concentration during induction treatment may be attributed to the activation of a natural antioxidative defence mechanism, endocrine influence on CoQ10 synthesis from steroid treatment, or a shift in CoQ10 from the damaged cells to the plasma after cell lysis.

Vitamin D status and parathyroid hormone in obese children before and after weight loss.

OBJECTIVE: The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children. METHODS: Fasting serum PTH, 1,25-OH Vit D, 25-OH Vit D, inorganic phosphate, calcium, alkaline phosphatase (AP), insulin, glucose, and weight status (SDS-BMI and percentage body fat) were determined in 133 obese children (median age 12.1 years) and compared with 23 non-obese children. Furthermore, these parameters were analyzed in 67 obese children before and after participating in a 1-year obesity intervention program. RESULTS: Obese children had significantly (P < 0.001) higher PTH and lower 25-OH Vit D concentrations compared with non-obese children, while calcium, phosphate, AP, and 1,25-OH Vit D did not differ significantly. Changes of PTH (r = 0.23, P = 0.031) and 25-OH Vit D (r = -0.27, P = 0.013) correlated significantly with changes of SDS-BMI, but not with changes of insulin sensitivity (homeostasis model assessment; HOMA-B%). Reduction of overweight in 35 children led to a significant (P < 0.01) decrease of PTH concentrations and an increase in 25-OH Vit D levels. CONCLUSIONS: PTH levels were positively and 25-OH Vit D concentrations were negatively related to weight status. Since these alterations normalized after weight loss, these changes are consequences rather than causes of overweight. A relationship between PTH, vitamin D, and insulin sensitivity based on the HOMA index was not found in obese children. Further longitudinal clamp studies are necessary to study the relationship between vitamin D and insulin sensitivity.

Enrichment of coenzyme Q10 in plasma and blood cells: defense against oxidative damage.

Coenzyme Q10 (CoQ10) concentration in blood cells was analyzed by HPLC and compared to plasma concentration before, during, and after CoQ10 (3 mg/kg/day) supplementation to human probands. Lymphocyte DNA 8-hydroxydeoxy-guanosine (8-OHdG), a marker of oxidative stress, was analyzed by Comet assay. Subjects supplemented with CoQ10 showed a distinct response in plasma concentrations after 14 and 28 days. Plasma levels returned to baseline values 12 weeks after treatment stopped. The plasma concentration increase did not affect erythrocyte levels. However, after CoQ10 supplementation, the platelet level increased; after supplementation stopped, the platelet level showed a delayed decrease. A positive correlation was shown between the plasma CoQ10 level and platelet and white blood cell CoQ10 levels. During CoQ10 supplementation, delayed formation of 8-OHdG in lymphocyte DNA was observed; this effect was long-lasting and could be observed even 12 weeks after supplementation stopped. Intracellular enrichment may support anti-oxidative defense mechanisms.

Definable somatic disorders in overweight children and adolescents.

OBJECTIVE: To analyze the frequencies and clinical presentation of definable somatic disorders in children who are overweight. STUDY DESIGN: We assessed prospectively 1405 children aged 4 to 16 years who were overweight and came to our specialized clinic for endocrinology and obesity with a standardized diagnostic procedure. In a subgroup of 223 children, we sought mutations in the melanocortin-4-receptor gene (MC4R). RESULTS: Endocrine or syndromal disorders were diagnosed in 13 children (<1%; 4 with hypothyroidism, 1 with Cushing's syndrome, 1 with growth hormone deficiency, 2 with pseudohypoparathyroidism, 1 with pseudopseudohypoparathyroidism, 2 with Prader-Willi syndrome, 1 with Bardet-Biedl syndrome, 1 with Klinefelter syndrome). A total of 85% of these children had short stature, in marked contrast to only 0.6% of the other children. Moderately elevated thyrotropin and cortisol concentrations were observed in 4% and 5%, respectively, of all children. Non-synonymous MC4R mutations were found in 6% of the children. CONCLUSIONS: In contrast to MC4R mutations, endocrine and clinically identifiable syndromal disorders were rare in children who were overweight and always associated with further symptoms. All children who are overweight with short stature or reduced growth velocity should be carefully examined for endocrine or syndromal disorders. A general screening with laboratory measurements cannot be recommended because thyrotropin and cortisol levels are frequently moderately elevated in children who are overweight, thus entailing further superfluous diagnostic procedures.

Comparison of metabolic syndrome prevalence using eight different definitions: a critical approach.

OBJECTIVE: Multiple definitions of the metabolic syndrome (MS) have been proposed for children, adolescents and adults. The aim of this study was to analyse the variations in the MS prevalence using different definitions and to examine which factors influence the frequency of the MS in childhood and adolescence. METHODS AND DESIGN: The prevalence of the MS according to eight proposed definitions was studied in 1205 Caucasian overweight children and adolescents aged 4-16 years (mean body mass index (BMI) 27.3 kg/m2, mean age 11.8 years, 46% males, 39% prepubertal). Blood pressure, waist circumference and fasting triglycerides, HDL-cholesterol, total cholesterol, insulin and glucose concentrations were determined. Overweight was defined according to the International Task Force of Obesity in Childhood. Degree of overweight was calculated as standard deviation score of BMI (SDS-BMI). Insulin resistance was estimated based on the HOMA model. RESULTS: The prevalence of the MS varied significantly (p<0.001), being between 6% and 39% depending on the different definitions. Only 2% of the children fulfilled the criteria of the MS in all definitions. Insulin resistance and degree of overweight were associated with the MS. In most definitions, pubertal stage did not influence the occurrence of the MS. In a principal component analysis, total cholesterol, triglycerides and waist circumference showed high final communality estimates. CONCLUSIONS: Since the prevalence of the MS varied widely in overweight children and adolescents depending on the proposed definition used, an internationally accepted uniform definition of the MS is necessary to compare different populations and studies.

Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention.

BACKGROUND: Data concerning the long-term improvement of cardiovascular disease (CVD) risk factors after an obesity intervention in children are limited. OBJECTIVE: We studied changes in weight status and CVD risk factors in children in an intervention program and evaluated whether these changes were sustained 1 y after the end of the intervention. DESIGN: We analyzed changes in the SD score (SDS) of body mass index [BMI; in kg/m2 (SDS-BMI)], blood pressure (BP), lipids, and homeostasis model assessment index of insulin resistance (HOMA-IR) over the course of 2 y in 240 obese (BMI > 97th percentile) children aged 6-14 y (x age: 10.4 y; x BMI: 26.9). Of these 240 children, 203 participated in a 1-y intervention program of physical exercise, nutrition education, and behavior therapy. We compared these children with 37 obese children who underwent no intervention and with 12 normal-weight children of the same age and sex. RESULTS: Obese children had significantly (P < 0.05) higher BP, HOMA-IR, and insulin, triacylglycerol, and LDL-cholesterol concentrations and lower HDL-cholesterol concentrations than did normal-weight children. Twenty-nine children dropped out of the intervention. Only in the 126 children who reduced their SDS-BMI did BP (8% and 12% decreases in systolic and diastolic BP, respectively), lipids (12% and 5% decreases in triacylglycerol and LDL cholesterol, respectively; 7% increase in HDL cholesterol), insulin (13% decrease), and HOMA-IR (17% decrease) improve significantly (P < 0.05). Reduction in SDS-BMI and all benefits regarding CVD risk factors were sustained 1 y after the end of the intervention in the children whose SDS-BMI decreased. CONCLUSIONS: Long-term multidisciplinary intervention led to a reduction in SDS-BMI in most of the obese children 1 y after the end of the intervention. Reduction in SDS-BMI was accompanied by an improvement in CVD risk factors.

Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids.

CONTEXT: There is some controversy whether T(4) treatment is indicated in obese humans with hyperthyrotropinemia. OBJECTIVE: The objective of this study was to examine whether hyperthyrotropinemia is a cause or a consequence of obesity. DESIGN: The study was designed as a cross-sectional comparison between obese and lean children and includes a 1-yr follow-up study. SETTING: The study was set in a primary care facility. PATIENTS: The patients were 246 obese and 71 lean children. INTERVENTION: The 1-yr intervention program was based on exercise, behavior therapy, and nutrition education. MAIN OUTCOME MEASURES: The main outcome measures were TSH, free T(3) (fT3), free T(4) (fT4), high-density lipoprotein, low-density lipoprotein, and total cholesterol at baseline and 1 yr later. RESULTS: TSH (P = 0.009) and fT3 (P = 0.003) concentrations were significantly higher in obese children than in normal weight children, whereas there was no difference in fT4 levels (P = 0.804). Lipids did not correlate significantly to thyroid hormones in cross-sectional and longitudinal analyses. fT3, fT4, and lipids did not differ significantly in the 43 (17%) children with TSH levels above the normal range from the children with TSH levels within the normal range. Substantial weight loss in 49 obese children led to a significant reduction of TSH (P = 0.035) and fT3 (P = 0.036). The 197 obese children without substantial weight loss demonstrated no significant changes of thyroid hormones. CONCLUSIONS: Because fT3 and TSH were moderately increased in obese children and weight loss led to a reduction, the elevation of these hormones seems to be rather a consequence of obesity than a cause of obesity. Because fT3 and TSH were both increased in obesity and thyroid hormones were not associated to lipids, we put forward the hypothesis that there is no necessity for thyroxine treatment.