Wieland Kiess

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.

New predictors of the metabolic syndrome in children: Role of adipocytokines

There is ample discussion of the relevance of the metabolic syndrome, the definition criteria, and predictive power. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Because children are otherwise relatively free of co-morbidities, they constitute an interesting population in which to study the sequence of events of obesity-related pathology. The adipocytokines appear to be important in this respect. Leptin was initially suggested as a promising “antiobesity” hormone. New concepts indicate that, in humans, leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors, but their role in children remains to be specified. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.

Body Mass Index, Waist Circumference, and Waist-to- Height Ratio as Predictors of Cardiometabolic Risk in Childhood Obesity Depending on Pubertal Development

CONTEXT The predictive value of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR) to define cardiometabolic risk is unclear in childhood obesity. OBJECTIVE [corrected] The associations between BMI, WtHR, or WC and cardiometabolic risk markers were analyzed in a multicenter data collection of obese youth. DESIGN AND SUBJECTS BMI, WtHR, and WC were retrospectively evaluated in 1278 patients (11-18 years, 53% boys) from the German/Austrian/Swiss Adiposity Patients Registry. MAIN OUTCOME MEASURES Parameters were correlated with homeostasis model assessment for insulin resistance, fasting insulin, blood pressure, transaminases, lipids and uric acid, applying adjusted regression models, with age group, pubertal stage and gender as covariates. RESULTS Homeostasis model assessment for insulin resistance and fasting insulin were most strongly correlated with BMI, independent of age group or gender. Lipids, transaminases, and uric acid were most strongly correlated with WC with stronger associations for boys. Correlations between BMI and WC as well as metabolic markers and systolic blood pressure showed only minor differences. The pattern of relationship changed during the course of pubertal development with the strongest associations for pubertal children. None of the parameters showed a dependency on WtHR that was superior to BMI or WC. CONCLUSIONS There is only small additional benefit in using WC measurements for routine pediatric care in addition to BMI for predicting metabolic risk. For all parameters, the relationship is strongest during midpuberty, emphasizing that among obese pubertal adolescents, anthropometric measures (BMI and WC) best predict cardiometabolic comorbidities. WtHR does not seem to be superior to BMI or WC in predicting metabolic or cardiovascular risk related to childhood obesity.

Leptin in maternal serum and breast milk: association with infants' body weight gain in a longitudinal study over 6 months of lactation.

The adipokine leptin has been detected in human breast milk, but its effect on postnatal growth and development remains largely unclear. We hypothesized that leptin could affect infants body weight gain during early lactation in the first 6 mo of life. Therefore, we evaluated leptin levels in maternal serum and breast milk of 23 healthy, lactating mothers and their neonates in a prospective, longitudinal study. Leptin concentration was quantified by a commercially available human leptin RIA. Our results showed that leptin levels in breast milk were 22-fold lower than in maternal serum, but both parameters were positively correlated to each other (r = 0.431, p = 0.001) and to maternal BMI (serum: r = 0.512, p < 0.001; milk: r = 0.298, p < 0.001) over 6 mo of lactation. A negative association was found between breast milk leptin levels during the first week after delivery and the infant weight gain from the end of the first to the sixth month (r = −0.681, p = 0.007). This suggests that milk-borne leptin provides a link between maternal body composition and infant growth and development and plays a critical role in regulating appetite and food intake during early infancy.

Serum irisin levels are regulated by acute strenuous exercise.

RATIONALE The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue. However, clinical and functional studies on the association of irisin with obesity, muscle mass, and metabolic status remain controversial. Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematically evaluated the influence of diurnal rhythm, anthropometric and metabolic parameters, and exercise on irisin. RESULTS Serum irisin levels did not show diurnal variations, nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing. Irisin levels decreased with age. In adults, irisin levels were higher in men than in women, and obese subjects had significantly higher levels than lean control subjects. Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass. Of the 4 exercise regimens that differed in duration and intensity, we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise (cycling ergometry) and a 30-minute bout of intensive exercise in children and young adults, whereas longer (6 weeks) or chronic (1 year) increases in physical activity did not affect irisin levels. SUMMARY We show that irisin levels are affected by age, sex, obesity, and particularly muscle mass, whereas diurnal rhythm and meals do not contribute to the variation in irisin levels. Short bouts of intensive exercise but not long-term elevations in physical activity, acutely and transiently increase serum irisin levels in children and adults.

Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study

OBJECTIVE Adiponectin plays an important role in pathophysiology of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to determine adiponectin concentrations in children and adolescents with type 1 diabetes in a longitudinal manner and to study the impact of age, gender, body mass index (BMI) and metabolic control. RESEARCH DESIGN AND METHODS In this study, 88 children and adolescents with type 1 diabetes were followed longitudinally. At baseline and during follow-up, serum levels of adiponectin were measured by enzyme-linked immunoassay and correlated with clinical data, HbA1c and lipids. Healthy children (n = 259) were chosen as a control group. RESULTS Serum adiponectin levels were significantly higher in children with type 1 diabetes compared with healthy children (13.1 vs 9.1 microg/ml at baseline, P < 0.001). Adiponectin concentrations inversely correlated with BMI s.d.s (P < 0.001). No significant difference of adiponectin levels regarding gender, diabetes duration or HbA1c was seen. Adiponectin concentrations decreased in males with type 1 diabetes during puberty (P = 0.03) while there was no significant change in females. In a subgroup of patients with new onset type 1 diabetes, adiponectin concentrations were not different from adiponectin levels in control subjects but increased during follow-up (P = 0.007). Stepwise multiple regression analysis showed that most important predictors of adiponectin levels in type 1 diabetes at the end of the study were adiponectin concentration at baseline (beta = 0.574, P < 0.001) and BMI s.d.s (beta = -0.302, P = 0.001, r2 = 0.56). CONCLUSIONS Children and adolescents with type 1 diabetes have BMI-dependent elevated serum concentrations of adiponectin compared with healthy children.

Polygenic Contribution to Obesity: Genome-Wide Strategies Reveal New Targets

Obesity results from the complex interaction of environmental factors that act on a genetic background that determines the susceptibility to obesity. The identification of such obesity susceptibility

Comorbidities Related to BMI Category in Children and Adolescents: German/Austrian/Swiss Obesity Register APV Compared to the German KiGGS Study

Purpose: To assess cardiovascular risk factors in overweight or obese children and adolescents in Germany, Austria and Switzerland and to investigate the relationship to BMI category. Methods: Data of 63,025 overweight or obese patients (APV population) were compared to normal-weight subjects from a representative study on health status of 14,298 children and adolescents in Germany (KiGGS survey). The weight status was assessed by BMI, and BMI-SDS values were cal-culated using national reference data. Results: In normal-weight KiGGS subjects, mean BMI was 17.3 ± 2.5 (BMI-SDS -0.1 ± 0.8). In the overweight or obese APV population, mean BMI was 30.2 ± 5.6 (BMI-SDS 2.5 ± 0.6). In normal-weight subjects blood pressure, total cholesterol, LDL-cholesterol, and triglycerides were elevated in 6.1, 8.6, 7.0 and 3.0%, respectively, and HDL-cholesterol was reduced in 3.0%, whereas in overweight/obese subjects the percentages of abnormal values were 35.3, 13.8, 14.5, 13.6, and 10.1%, respectively. Conclusions: Cardiovascular risk is increased in obese children and adolescents. There is a strong need to monitor blood pressure and serum lipids in this group of patients. Our results emphasize the importance of prevention of obesity in order to reduce cardiovascular risk.

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

OBJECTIVE Congenital adrenal hyperplasia (CAH) patients are at a higher risk to develop obesity. The role of leptin in CAH is still controversial. Our study aimed to evaluate serum levels of leptin, the soluble leptin receptor (sOB-R), and the sOB-R: leptin molar ratios in a cohort of CAH children and adolescents, and their associations with clinical and metabolic parameters. METHODS We studied 51 CAH patients, aged 5.6-19.6 years (median 11.8, n=30 females) cross-sectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. Blood specimens were taken after overnight fasting between 0800 and 1000 h. For the analyses of leptin and sOB-R, matched pairs were built with healthy Caucasian patients for sex, Tanner stage (TS), chronologic age (CA), and body mass index (BMI). RESULTS BMI and SDS were significantly elevated compared with the reference population. Leptin levels were not different between matched pairs, whereas sOB-R levels were significantly lower in CAH. Consequently, the sOB-R: leptin molar ratios were significantly decreased in CAH. Correlation analyses in CAH patients revealed significant relationship between leptin and CA, TS, BMI, and homeostasis model assessment of insulin resistance. Similar results were obtained for the matched control group. For sOB-R, we found no significant correlation for CA, TS, or BMI in CAH, but we did in the controls. There were significant correlations for androgens within the CAH group. Additional analyses revealed no correlation with steroid medication or metabolic control. CONCLUSIONS Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH.

Comparison of adrenal function tests in children--the glucagon stimulation test allows the simultaneous assessment of adrenal function and growth hormone response in children.

The accurate assessment of adrenal function is necessary in many children with suspicion of pituitary insufficiency. The objective of this study was to evaluate the adrenal response during the glucagon stimulation test (GST) and its diagnostic utility in children. A total of 290 children, aged 10.1 +/- 5.0 years, were evaluated for adrenal function using the corticotrophin releasing hormone (CRH) test, the GST, and/or the insulin tolerance test (ITT). Glucagon stimulation provoked a substantial rise in cortisol and adrenocorticotropin (ACTH) that was independent of gender, age, or underlying growth hormone deficiency. There were no differences in peak cortisol levels in the GST compared to the CRH test in pair-wise intra-individual analyses in children with both tests performed within one year (615.4 +/- 30.5 vs 602.8 +/- 22.4 nmol/l, n=52). Similarly, there were no differences in the cortisol response between the ITT and CRH test. Peak cortisol levels in the CRH test correlated with the GST and the ITT. The magnitude of ACTH response, in contrast, was highest in the ITT with a 9.8-fold increase over baseline, while the increase in the GST (3.1-fold) and CRH test (1.6-fold) were more subtle. Since there is controversy concerning reliable cut-off values for adrenal function tests in children, we analyzed cut off levels in 186 children, including 26 children with adrenal insufficiency, using the CRH test. A peak cortisol level of 450 nmol/l provided the best balance of sensitivity (88.5%) and specificity (86.8%), while higher cut-off levels did not increase sensitivity but lost in specificity. In summary, the GST constitutes an1 equally sensitive test for the assessment of adrenal function in children that is not confounded by anthropometric parameters and is generally not accompanied by major side effects. It allows the simultaneous assessment of corticotroph and somatotroph function and may thus constitute a valuable alternative to the ITT.