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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Paediatric cancer pain management using the WHO analgesic ladder--results of a prospective analysis from 2265 treatment days during a quality improvement study.

OBJECTIVE: To collect data on pain management in paediatric oncology with respect to the WHO ladder approach. SETTING, DESIGN, PATIENTS AND METHODS: Eight German tertiary care paediatric oncology centres prospectively documented all their in-patient pain treatment courses from June 1999 to December 2000. Pain was scored using a 1-6 faces scale. RESULTS: Two hundred and twenty four patients (median age, 9 years; range 0.2-32.1) were enrolled. Three hundred and thirty three pain episodes comprising a total of 2265 treatment days were documented. Pain was mostly therapy associated. The most frequently administered non-opioid analgesics were dipyrone and paracetamol. On WHO step 2, tramadol was almost the only opioid used. During tramadol monotherapy average daily pain scores were lower than with a combination of tramadol and non-opioid analgesics. On WHO step 3, morphine was at least part of the analgesic regimen on most treatment days. Strong opioids were combined with a non-opioid analgesic on 41% of the treatment days. The mean intravenous morphine equivalence dose was 0.034 mg/kg/h. During opioid and non-opioid combination therapy, adverse effects were more frequent, and average pain scored higher than on opioid monotherapy. CONCLUSIONS: WHO-guidelines were closely followed in Germany and seem to provide effective analgesia for children with cancer pain. In our patient group there is no evidence that a combination of an opioid with a non-opioid is more effective than opioid therapy alone in in-patient paediatric oncology pain treatment.

Coenzyme Q10 concentration in plasma and blood cells: what about diurnal changes?

Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant and performs essential functions in mitochondrial energy production. The value of CoQ10 as a biomarker for oxidative stress will be severely restricted if there are huge individual daily variations in its concentration. For analysis of diurnal changes in CoQ10 plasma and blood cell concentrations, blood was collected from nine healthy adults (at two- or three-hour intervals for plasma, and three times a day for blood cells). CoQ10 was analysed by HPLC using electrochemical detection and internal standardisation. Daytime variations in CoQ10 concentration in plasma are maintained within narrow limits and show no statistically significant difference (Kruskal-Wallis). However, a drop at night-time (0300 h) is accompanied by a drop in total cholesterol concentration. Remarkable inter-individual differences in blood cell (erythrocytes, platelets, white blood cells) content of CoQ10 occur with only slight intra-individual daily variations. A correlation (Spearman) is found for cholesterol and CoQ10 content in circulation which may be explained by the carrier capacity of blood for this highly lipophilic substance. Moreover, a diurnal change in hepatic HMG-CoA reductase activity may suggest a common diurnal regulation of synthesis of both CoQ10 and cholesterol.

Androgens before and after weight loss in obese children.

CONTEXT: Little information is available on androgens in obese children, and it is unknown whether these hormones change after weight loss. OBJECTIVE: The objective of this study was to compare androgens between obese and normal-weight children and to study the effect of weight loss on androgens. DESIGN: The design was a cross-sectional comparison between obese and normal-weight children separated according to pubertal stage and longitudinal 1-yr follow-up study in obese children participating in a weight-loss intervention. SETTING: The setting of this study was a primary care facility. PATIENTS: A total of 273 obese and 79 lean children (aged 4-14 yr) were studied, including a subgroup of 155 obese children for the longitudinal study. INTERVENTION: The intervention program was an outpatient 1-yr intervention program based on exercise, behavior, and nutrition therapy (high-carbohydrate low-fat diet). MAIN OUTCOME MEASURES: The outcome measures included testosterone and dehydroepiandrosterone sulfate (DHEAS) at baseline and 1 yr later. RESULTS: The obese prepubertal children and the obese pubertal girls showed significantly (P < 0.01) higher testosterone and DHEAS levels, whereas obese pubertal boys did not significantly differ in androgens from their lean counterparts. Significant correlations with body mass index were demonstrated in multivariate regression analyses for DHEAS in all children and for testosterone in prepubertal children and in pubertal girls. The obese prepubertal children and obese girls losing substantial weight showed a significant (P < 0.05) decrease in their testosterone concentrations. CONCLUSIONS: Moderately increased testosterone and DHEAS levels were found in obese prepubertal children and in obese pubertal girls, whereas androgen concentrations did not differ between obese and normal-weight pubertal boys. Weight loss induced a decrease in testosterone in obese prepubertal children and pubertal girls pointing to a reversible increase of androgens.

Insulin sensitivity indices of glucose and free fatty acid metabolism in obese children and adolescents in relation to serum lipids.

OBJECTIVE: Most studies concerning the association between insulin resistance and the features of metabolic syndrome in obese children are based on measurement of insulin sensitivity indices (ISI) of glucose metabolism and not of fat metabolism. METHODS: We studied fasting low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, insulin, free fatty acids (FFA), blood glucose, ISI of glucose (homeostasis model assessment [HOMA] %S), and FFA metabolism (ISI-FFA) in 124 obese children aged 6 to 16 years. ISI-FFA was calculated based on the formula 2/(insulin x FFA + 1). Stepwise forward regression analyses were performed with triglycerides, HDL-C and LDL-C as dependent variables and age, sex, stage of puberty, body mass index, insulin, FFA, and blood glucose as independent variables. Direct multiple regression analyses were conducted with the dependent variables triglycerides, HDL-C, and LDL-C including age, sex, stage of puberty, body mass index, HOMA %S, and ISI-FFA as independent variables. Furthermore, ISI-FFA was measured in 13 normal-weight children aged 6 to 16 years. RESULTS: ISI-FFA (median 0.30) was significantly (P < .05) reduced in obese children compared with normal-weight children (median ISI-FFA 0.64). In stepwise regression analyses, triglycerides were significantly correlated with insulin and FFA (P < .05), LDL-C levels were significantly correlated with FFA (P < .05), and HDL-C was related to stage of puberty (P < .05), whereas all other variables demonstrated no significant associations with triglycerides, LDL-C, and HDL-C levels. In contrast to HOMA %S, ISI-FFA was significantly (P < .05) related to triglycerides and LDL-C in direct multiple regression analysis. CONCLUSIONS: Insulin resistance in respect to FFA metabolism is already detectable in childhood. Insulin sensitivity index of FFA metabolism seems to be a better tool for describing insulin resistance in lipid metabolism than ISI of glucose metabolism, because FFA and partially insulin but not glucose were related to triglycerides and LDL-C.

High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children.

To confirm the existence of obesity-induced inflammation and to clarify the association between such inflammation and other cardiovascular risk factors, we investigated the relationships between high-sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), obesity, blood pressure, lipids, and insulin resistance in a long-term follow-up of obese children. We compared the serum concentrations of hsCRP, TNF-alpha, high-density lipoprotein cholesterol, and triglycerides as well as blood pressure and the insulin resistance index (homeostasis model assessment [HOMA]) of 14 nonobese and 31 obese children. Furthermore, we studied the changes in these parameters in 16 obese children who lost weight and in 15 obese children without weight change over a 1-year period. In the obese children, blood pressure (P=.003), HOMA (P=.034), and triglyceride (P=.011), TNF-alpha (P=.015), and hsCRP (P<.001) levels were significantly higher, whereas high-density lipoprotein cholesterol concentrations were significantly (P=.015) lower compared with the nonobese children. Weight loss was associated with a significant decrease in hsCRP (P=.008) and triglyceride (P=.048) levels, HOMA (P<.001), and blood pressure (P=.019), whereas there were no significant changes in the children with stable weight status. The changes in hsCRP and TNF-alpha levels over the 1-year period were not significantly correlated to the changes in lipids, blood pressure, and HOMA. Obese children demonstrated significantly higher levels of hsCRP and TNF-alpha compared with nonobese children. The chronic inflammation markers TNF-alpha and hsCRP were independent of lipids, blood pressure, and insulin resistance index. Weight loss was associated with the significant decrease of hsCRP and triglyceride levels, and blood pressure.

Pain in pediatric oncology--children's and parents' perspectives.

There is a lack of valid epidemiological data on malignancy-associated pain in modern pediatric oncology. Pediatric oncology patients (self-assessment) and their parents from 28 hospitals were questioned using age-adapted, structured interviews and validated pain assessment tools. Pain intensity was measured by the NRS and Bieri faces scale. We conducted 363 interviews with patients and their parents, and 46 with the parents alone (if patients <2.5 years). Pain was reported at the time of the interview or within the last 24 h, 7 d, or 4 weeks in 15%, 28%, 50% and 58% of cases, respectively. The proportion of patients suffering severe to maximal pain (NRS>3; Bieri>2) increased significantly (p=0.001, chi2 test). The median pain intensity for the most severe pain episode within the last 4 weeks was 6.7 (NRS 0-10). Adverse effects of anti-tumor therapy were the most frequent cause of pain. Multivariate analyses depicted general physical condition either "severely reduced" (ASA status 3) (OR 4.0, 95% CI 1.1-14.7, p=0.037) or "moderately reduced" (ASA status 2) (OR 1.8, 95% CI 1.1-2.9, p=0.018), "in-patient status" (OR 1.8, 95% CI 1.2-2.9, p=0.010), and "co-morbidity present" (OR 3.5, 95% CI 1.1-10.7, p=0.030) as risk factors for severe to maximal pain. General anesthesia was the only factor significantly (OR 0.14, 95% CI 0.05-0.39, p<0.01) associated with a reduction in the proportion of patients suffering severe to maximal pain during bone marrow aspiration. Our data emphasize both the importance of in-house acute pain control and the need for general anesthesia during painful procedures in pediatric oncology.