Pharmacotherapy in Childhood Obesity

Background: The increasing number of obese children and adolescence is a major problem in health-care systems. Currently, the gold standard for the treatment of these patients with obesity is a multicomponent lifestyle intervention. Unfortunately, this strategy is not leading to a substantial and long-lasting weight loss in the majority of patients. This is the reason why there is an urgent need to establish new treatment strategies for children and adolescents with obesity to reduce the risk for the development of any comorbidities like cardiovascular diseases or diabetes mellitus type 2. Summary: In this review, we outline available pharmacological therapeutic options for children and compare the available study data with the outcome of conservative treatment approaches. Key Messages: We discussed, in detail, how knowledge about underlying molecular mechanisms might support the identification of effective antiobesity drugs in the future and in which way this might modulate current treatment strategies to support children and adolescence with obesity to lose body weight

Comparison of two methods of cardiopulmonary exercise testing for assessing physical fitness in children and adolescents with extreme obesity

It is well-known that children and adolescents with obesity have increased over recent decades which in turn carries greater risk of co-morbidities and poses a preventive as well as a therapeutic challenge. Currently, there are limited recommendations available on proven methods for recording physical fitness in children and adolescents presenting with extreme obesity. In this study, twenty participants, aged 12–17 years, with a body mass index (BMI) above the 99.5th percentile, were comparatively assessed, using a correlation between their physical fitness on a bicycle (BC) and treadmill (TM) cardiopulmonary exercise testing (CPET) with a lactate diagnostic. The results of the BC and the TM were as follows: maximum heart rate ( HRmax) 186.4 ± 8.6 beats per minute (bpm) vs. 190.8 ± 8.8 bpm, peak oxygen consumption ( VO2peak/kg) 23.5 ± 2.9 ml/min/ kg vs. 25.4 ± 3.1 ml/min/kg, and maximum lactate ( Lamax) 6.4 ± 1.6 mmol/l vs. 5.6 ± 1.4 mmol/l. The values of HRmax and VO2peak/ kg were significantly higher for adolescents tested on the TM. However, no significant difference was observed in either Lamax values or between the genders. Conclusions: The higher values of HRmax and VO2peak/ kg could be attributed to the activation of a higher percentage of muscle mass on the TM. Lower Lamax values on the TM suggest maximum physical exertion was not achieved. This could be due to the extreme body weight carried by the participants. Both the BC and the TM CPET could be used for assessing physical fitness in children and adolescents with extreme obesity but should not be used interchangeably.Peer Reviewe

Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength

Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves' ophthalmopathy. Other physiological roles of natural IGF1R-aAb are not known. We hypothesized that IGF1R-aAb may be related to muscle development. Serum samples (n = 408) from young overweight subjects (n = 143) were collected during a lifestyle intervention study. Anthropometric parameters, along with leptin, IGF1 and IGF1R-aAb concentrations, were analyzed, and the subjects were categorized into positive or negative for IGF1R-aAb. Eleven out of 143 subjects (7.7%) were positive for IGF1R-aAb. Identified IGF1R-aAb were molecularly characterized and showed antagonistic activity in vitro impairing IGF1-mediated IGF1R activation. Mean body weight, height or age were similar between IGF1R-aAb-positive and -negative subjects, but IGF1 concentrations differed. Jumping ability, as well as right and left handgrip strengths, were lower in the IGF1R-aAb-positive as compared to the IGF1R-aAb-negative subjects. We conclude that natural IGF1R-aAb are detectable in apparently healthy subjects and are capable of antagonizing IGF1-dependent IGF1R activation. Moreover, the presence of IGF1R-aAb is associated with poor physical strength. Although the causality of this association is unclear, the data imply a potential influence of IGF1R autoimmunity on muscle development

Applying a correction procedure to the prevalence estimates of overweight and obesity in the German part of the HBSC study

Background: Prevalence rates for overweight and obesity based on self-reported height and weight are underestimated, whereas the prevalence rate for underweight is slightly overestimated. Therefore a correction is needed. Aim of this study is to apply correction procedures to the prevalence rates developed on basis of (self-reported and measured) data from the representative German National Health Interview and Examination Survey for Children and Adolescents (KiGGS) to (self-reported) data from the German Health Behaviour in School Aged Children (HBSC) study to determine whether correction leads to higher prevalence estimates of overweight and obesity as well as lower prevalence rates for underweight. Methods: BMI classifications based on self-reported and measured height and weight from a subsample of the KiGGS study (2,565 adolescents aged 11–15) were used to estimate two different correction formulas. The first and the second correction function are described. Furthermore, the both formulas were applied to the prevalence rates from the HBSC study (7,274 adolescents aged 11–15) which are based on self-reports collected via self-administered questionnaires. Results: After applying the first correction function to self-reported data of the HBSC study, the prevalence rates of overweight and obesity increased from 5.5% to 7.8% (compared to 10.4% in the KiGGS study) and 2.7% to 3.8% (compared to 7.8% in the KiGGS study), respectively, whereas the corrected prevalence rates of underweight and severe underweight decreased from 8.0% to 6.7% (compared to 5.7% in the KiGGS study) and from 5.5% to 3.3% (compared to 2.4% in the KiGGS study), respectively. Application of the second correction function, which additionally considers body image, led to further slight corrections with an increase of the prevalence rates for overweight to 7.9% and for obese to 3.9%. Conclusion: Subjective BMI can be used to determine the prevalence of overweight and obesity among children and adolescents. Where there is evidence of bias, the prevalence estimates should be corrected using conditional probabilities that link measured and subjectively assessed BMI from a representative validation study. These corrections may be improved further by considering body image as an additional influential factor

Results from the KiGGS Study

Objective: The use of reported instead of measured height and weight induces a bias in prevalence rates for overweight and obesity. Therefore, correction formulas are necessary. Methods: Self-reported and measured height and weight were available from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) baseline study (2003-2006) from 3,468 adolescents aged 11-17 years. With regression analyses, correction formulas for height and weight were developed. Cross-validation was conducted in order to validate and compare the formulas. Corrected BMI was calculated, and corrected prevalence rates were estimated. Sensitivity, specificity, and predictive values for overweight and obesity were calculated. Results: Through the correction procedure, the mean differences between reported and measured height and weight become remarkably smaller and thus the estimated prevalence rates more accurate. The corrected proportions for overweight and obesity are less under-reported, while the corrected proportions for underweight are less over-reported. Sensitivity for overweight and obesity increased after correction. Specificity remained high. Conclusion: The validation process showed that the correction formulas are an appropriate tool to correct self- reports on an individual level in order to estimate corrected prevalence rates of overweight and obesity in adolescents for studies which have collected self-reports only

Tissue Sodium Content and Arterial Hypertension in Obese Adolescents

Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na+) homeostasis in this process is incompletely understood, yet correlations between Na+ accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13-17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matched controls, underwent 23Na-MRI of the left lower leg with a standard clinical 3T scanner. Median triceps surae muscle Na+ content in hypertensive obese (11.95 mmol/L [interquartile range 11.62-13.66]) was significantly lower than in normotensive obese (13.63 mmol/L [12.97-17.64]; p = 0.043) or controls (15.37 mmol/L [14.12-16.08]; p = 0.012). No significant differences were found between normotensive obese and controls. Skin Na+ content in hypertensive obese (13.33 mmol/L [11.53-14.22] did not differ to normotensive obese (14.12 mmol/L [13.15-15.83]) or controls (11.48 mmol/L [10.48-12.80]), whereas normotensive obese had higher values compared to controls (p = 0.004). Arterial hypertension in obese adolescents is associated with low muscle Na+ content. These findings suggest an early dysregulation of Na+ homeostasis in cardiometabolic disease. Further research is needed to determine whether this association is causal and how it evolves in the transition to adulthood

Dietary Patterns in Adolescent Obesity as Predictors of Long-Term Success Following an Intensive Inpatient Lifestyle Programme

(1) Background: Lifestyle interventions for adolescents with obesity show minor long-term effects on anthropometric parameters. The persistence of dietary changes after obesity inpatient rehabilitation has not been sufficiently investigated. (2) Objectives: To analyse dietary patterns in German adolescents with obesity as predictors of long-term success following an intensive inpatient lifestyle programme regarding food choices as well as body weight and comorbidities. (3) Methods: Food consumption data of 137 German adolescents with obesity aged 10-17 years were collected by a nutrition interview. Cluster analysis was used to group the participants according to their food consumption. Dietary patterns, changes in body weight and insulin resistance were compared over a 2-year-period. (4) Results: Three dietary patterns were identified. Big Eaters (n = 32) consume high amounts of total sugar and meat, Moderate Eaters (n = 66) have a diet comparable to the national average, and Snackers (n = 39) have a particularly high consumption of total sugar. Big Eaters and Snackers significantly reduced the consumption of total sugar. Among Moderate Eaters, no persistent changes were observed. (5) Conclusion: Weight reduction interventions can induce long-lasting changes in the diet of adolescents with obesity. Therefore, the success of a weight reduction intervention should not be determined by weight reduction only

An Alu Element–Associated Hypermethylation Variant of the POMC Gene Is Associated with Childhood Obesity

The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron2–exon3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon3 methylation variant seems to result from an Alu element–triggered default state of methylation boundary definition. Exon3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity

Development and Validation of Correction Formulas for Self-Reported Height and Weight to Estimate BMI in Adolescents. Results from the KiGGS Study

Objective: The use of reported instead of measured height and weight induces a bias in prevalence rates for overweight and obesity. Therefore, correction formulas are necessary. Methods: Self-reported and measured height and weight were available from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) baseline study (2003-2006) from 3,468 adolescents aged 11-17 years. With regression analyses, correction formulas for height and weight were developed. Cross-validation was conducted in order to validate and compare the formulas. Corrected BMI was calculated, and corrected prevalence rates were estimated. Sensitivity, specificity, and predictive values for overweight and obesity were calculated. Results: Through the correction procedure, the mean differences between reported and measured height and weight become remarkably smaller and thus the estimated prevalence rates more accurate. The corrected proportions for overweight and obesity are less under-reported, while the corrected proportions for underweight are less over-reported. Sensitivity for overweight and obesity increased after correction. Specificity remained high. Conclusion: The validation process showed that the correction formulas are an appropriate tool to correct self-reports on an individual level in order to estimate corrected prevalence rates of overweight and obesity in adolescents for studies which have collected self-reports only

Erratum to : Updated prevalence rates of overweight and obesity in 11- to 17-year-old adolescents in Germany. Results from the telephone-based KiGGS Wave 1 after correction for bias in self-reports

Background: The nationwide “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS), conducted in 2003–2006, showed an increase in the prevalence rates of overweight and obesity compared to the early 1990s, indicating the need for regularly monitoring. Recently, a follow-up—KiGGS Wave 1 (2009–2012)—was carried out as a telephone-based survey, providing self-reported height and weight. Since self-reports lead to a bias in prevalence rates of weight status, a correction is needed. The aim of the present study is to obtain updated prevalence rates for overweight and obesity for 11- to 17-year olds living in Germany after correction for bias in self-reports. Methods: In KiGGS Wave 1, self-reported height and weight were collected from 4948 adolescents during a telephone interview. Participants were also asked about their body perception. From a subsample of KiGGS Wave 1 participants, measurements for height and weight were collected in a physical examination. In order to correct prevalence rates derived from self-reports, weight status categories based on self-reported and measured height and weight were used to estimate a correction formula according to an established procedure under consideration of body perception. The correction procedure was applied and corrected rates were estimated. Results: The corrected prevalence of overweight, including obesity, derived from KiGGS Wave 1, showed that the rate has not further increased compared to the KiGGS baseline survey (18.9 % vs. 18.8 % based on the German reference). Conclusion: The rates of overweight still remain at a high level. The results of KiGGS Wave 1 emphasise the significance of this health issue and the need for prevention of overweight and obesity in children and adolescents