Werner Andler

Insulin sensitivity among obese children and adolescents, according to degree of weight loss.

Objective. Insulin sensitivity is impaired among some obese children, reflecting an atherogenic risk factor profile for the affected subjects. This study was performed to examine the amount of weight reduction required to improve insulin sensitivity. Methods. We studied changes in insulin sensitivity indices (ISIs) for glucose metabolism (homeostasis model assessment and quantitative insulin sensitivity check index) and fat metabolism (free fatty acids) during a 1-year period among obese children who attended an obesity intervention program. The children were divided into 4 groups according to their changes in body mass index (BMI) SD score (SDS), as follows: group I, decrease in SDS-BMI of ≥0.5; group II, decrease in SDS-BMI of ≥0.25 to <0.5; group III, decrease in SDS-BMI of <0.25; group IV, increase in SDS-BMI. Results. Fifty-seven obese children (age range: 6–14 years; median age: 10 years; 46% boys) were included in the study. The 4 groups did not differ with respect to age, gender, degree of overweight (SDS-BMI), or ISI values at baseline. An increase in SDS-BMI (group IV, n = 12) was followed by a significant decrease in ISI values. The ISIs improved for group I (n = 9), whereas there were no significant changes in these parameters for group II (n = 21) and group III (n = 15). Conclusions. During a 1-year period, an increase in weight among obese children was associated with a decrease in insulin sensitivity. Weight loss was followed by significant improvement in insulin sensitivity for glucose and fat metabolism but only if the SDS-BMI decreased by ≥0.5 during the 1-year period.

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.

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.

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.

Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in obese youth. Lifestyle intervention was demonstrated to improve NAFLD but follow-up studies after end of intervention are lacking. Furthermore the necessary degree of overweight reduction for improvement of NAFLD remains unknown. Methods: We examined standard deviation score of body mass index (SDS-BMI) and transaminases in 152 obese children with NAFLD diagnosed by ultrasound at baseline, at the end of a 1-year intervention and 2 years after baseline. Within-subject changes of these parameters were compared by participation in the intervention based on physical activity, nutrition education and behaviour therapy. Results: In contrast to 43 children without lifestyle intervention, participation in lifestyle intervention (n = 109) was associated with a significant decrease of transaminases and overweight 1 and 2 years after baseline (1 year: alanine transaminase (ALT) −10 U/l (−14 to −6); aspartate transaminase (AST) −5 U/l (−7 to −3); SDS-BMI −0.23 (−0.30 to −0.16); 2 years: ALT −9 U/l (−12 to −6); AST −6 U/l (−7 to −4); SDS-BMI −0.30 (−0.37 to −0.22); data as mean changes and 95% confidence interval compared to baseline). Any degree of overweight reduction was associated with a significant decrease of NAFLD prevalence. The greatest decrease of NAFLD prevalence (1 year: −89% (95% CI −72% to −100%); 2 years: −94% (95% CI −83% to −100%)) was observed in children with the greatest overweight reduction (SDS-BMI decrease >0.5). Conclusions: Multidisciplinary lifestyle intervention is effective to improve NAFLD even in the 1-year follow-up after the end of intervention. A minimal reduction of overweight led to an improvement of NAFLD. Trial registration number: NCT00435734.

Cortisol and its relation to insulin resistance before and after weight loss in obese children.

Background: Insulin resistance occurs both in obesity and in Cushing’s syndrome suggesting a pathogenetic role of cortisol in insulin-resistant obese subjects. Methods: We examined serum cortisol in 81 insulin-resistant (homeostasis model assessment (HOMA) >4) obese children (age in median 12 years) and 151 obese children without insulin resistance (HOMA ≤4) (age in median 10 years) and compared these to cortisol of 83 healthy children of normal weight (age in median 12 years). Multivariate linear regression analysis was conducted for the dependent variable insulin resistance (HOMA), including weight status (BMI), age, gender, pubertal stage and cortisol concentration as independent variables. Furthermore, we analyzed cortisol and insulin resistance in 45 obese children with significant weight loss (reduction in SDS-BMI ≧0.5) and in 109 obese children without significant weight loss (reduction in SDS-BMI <0.5) over the time period of 1 year. Results: Cortisol was significantly (p = 0.006) higher in obese insulin-resistant children (median 14.6 µg/dl) compared to those of normal weight (median 11.4 µg/dl) or obese without insulin resistance (median 11.7 µg/dl). Insulin resistance was significantly influenced by weight status (BMI), age and cortisol using multivariate linear regression analysis. A reduction in overweight showed a significant decrease in cortisol (p = 0.005) and insulin resistance (p = 0.002) in insulin-resistant children, whilst there were no significant changes in children not reducing their overweight and in non-insulin-resistant children. Conclusions: Cortisol was moderately increased in insulin-resistant, obese children and related to insulin resistance. Weight reduction led to a decrease in cortisol and insulin resistance. These facts point to an association between cortisol and insulin resistance in obesity.

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, χ2 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.

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.

Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

Abstract:  Background:  Insulin resistance is well recognized both in type 1 diabetes mellitus (T1DM) and in obesity. Studies concerning the relation between insulin resistance and overweight in T1DM have not yet been carried out.

Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia

BACKGROUND The membrane-associated antioxidant coenzyme Q10 (CoQ10) or ubiquinone-10 is frequently measured in serum or plasma. However, little is known about the total contents or redox status of CoQ10 in blood cells. METHODS We have developed a method for determination of CoQ10 in erythrocytes. Total CoQ10 in erythrocytes was compared to the amounts of ubiquinone-10 and ubihydroquinone-10 in plasma using high-pressure liquid chromatography (HPLC) with electrochemical detection and internal standardisation (ubiquinone-9, ubihydroquinone-9). RESULTS Investigations in 10 healthy probands showed that oral intake of CoQ10 (3 mg/kg/day) led to a short-term (after 5 h, 1.57+/-0.55 pmol/microl plasma) and long-term (after 14 days, 4.00+/-1.88 pmol/microl plasma, p<0.05 vs. -1 h, 1.11+/-0.24 pmol/microl plasma) increase in plasma concentrations while decreasing the redox status of CoQ10 (after 14 days, 5.37+/-1.31% in plasma, p<0.05 vs. -1 h, 6.74+/-0.86% in plasma). However, in these healthy probands, CoQ10 content in red blood cells remained unchanged despite excessive supplementation. In addition, plasma and erythrocyte concentrations of CoQ10 were measured in five patients suffering from sickle cell anemia, a genetic anemia characterised by an overall accelerated production of reactive oxygen species. While these patients showed normal or decreased plasma levels of CoQ10 with a shifting of the redox state in favour of the oxidised part (10.8-27.2% in plasma), the erythrocyte concentrations of CoQ10 were dramatically elevated (280-1,093 pmol/10(9) ERY vs. 22.20+/-6.17 pmol/10(9) ERY). CONCLUSIONS We conclude that normal red blood cells may regulate their CoQ10 content independently from environmental supplementation, but dramatic changes may be expected under pathological conditions.