Clinical characteristics and outcomes of children, adolescents and young adults with overweight or obesity and mental health disorders.

BACKGROUND: Mental disorders are important comorbidities in youth with obesity. Aim was to describe the clinical characteristics and outcome of youth with overweight or obesity having comorbid mental disorders. METHODS: Data from children, adolescents, and young adults (age 6-30 years) with overweight or obesity and mental disorders (depression, anxiety disorder, eating disorder, attention deficit disorder (ADHD)) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry (APV) were analyzed and compared with those without reported mental disorders using regression modeling. RESULTS: Mental health comorbidity was reported in a total of 3969 out of 114,248 individuals with overweight or obesity: 42.5% had ADHD, 31.3% anxiety disorders, 24.3% depression, and 12.9% eating disorders. Being male (OR 1.39 (95%CI 1.27;1.52)), of older age (1.42 (1.25;1.62)), or with extreme obesity (1.45 (1.30;1.63)) were most strongly associated with mental health comorbidity. Regression analysis showed that mean BMI-SDS was significantly higher in the group of individuals with depression and eating disorders (BMI-SDS 2.13 (lower; upper mean:2.09;2.16) and 2.22 (2.17;2.26)) compared to those without reported mental health comorbidity (BMI-SDS 2.008 (2.005;2.011); p < 0.001). In youth with ADHD, BMI-SDS was lower compared to those without reported mental disorders (BMI-SDS 1.91 (1.89;1.93) vs 2.008 (2.005;2.011); p < 0.001). Proportion of severe obesity was higher in individuals with depression (23.7%), anxiety disorders (17.8%), and eating disorders (33.3%), but lower in ADHD (10.3%), compared to those without reported mental disorders (13.5%, p < 0.002). Proportions of dyslipidaemia and abnormal carbohydrate metabolism were not different in youth with and without reported mental health comorbidity. BMI-SDS change after one year of lifestyle intervention program ranged between -0.22 and -0.16 and was similar in youth without and with different mental disorders. CONCLUSION: Health care professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders and regular mental health screening should be considered.

[Improved Care and Treatment Options for Patients with Hyperphagia-Associated Obesity in Bardet-Biedl Syndrome]. / Verbesserte Versorgungs-und Behandlungsoptionen für Patienten mit Hyperphagie-assoziierter Adipositas bei Bardet-Biedl-Syndrom.

Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive multisystem disease. The pathophysiological origin is a dysfunction of the primary cilium. Clinical symptoms are heterogeneous and variable: retinal dystrophy, obesity, polydactyly, kidney abnormalities, hypogenitalism and developmental delays are the most common features. By the approval of the melanocortin 4 receptor agonist setmelanotide, a drug therapy for BBS-associated hyperphagia and obesity can be offered for the first time. Hyperphagia and severe obesity represent a considerable burden and are associated with comorbidity and increased mortality risk. Due to the limited experience with setmelanotide in BBS, a viable comprehensive therapy concept is to be presented. Therapy decision and management should be conducted in expert centers. For best therapeutic effects with setmelanotide adequate information of the patient about the modalities of the therapy (daily subcutaneous injection) and possible adverse drug events are necessary. Furthermore, the involvement of psychologists, nutritionists and nursing services (support for the application) should be considered together with the patient. The assessment of therapy response should be carried out with suitable outcome measurements and centrally reported to an adequate register.

A prospective analysis of the long-term impact of the COVID-19 pandemic on well-being and health care among children with a chronic condition and their families: a study protocol of the KICK-COVID study.

BACKGROUND: There is consistent evidence that the COVID-19 pandemic is associated with an increased psychosocial burden on children and adolescents and their parents. Relatively little is known about its particular impact on high-risk groups with chronic physical health conditions (CCs). Therefore, the primary aim of the study is to analyze the multiple impacts on health care and psychosocial well-being on these children and adolescents and their parents. METHODS: We will implement a two-stage approach. In the first step, parents and their underage children from three German patient registries for diabetes, obesity, and rheumatic diseases, are invited to fill out short questionnaires including questions about corona-specific stressors, the health care situation, and psychosocial well-being. In the next step, a more comprehensive, in-depth online survey is carried out in a smaller subsample. DISCUSSION: The study will provide insights into the multiple longer-term stressors during the COVID-19 pandemic in families with a child with a CC. The simultaneous consideration of medical and psycho-social endpoints will help to gain a deeper understanding of the complex interactions affecting family functioning, psychological well-being, and health care delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

What should governments be doing to prevent diabetes throughout the life course?

Health systems and governments are increasingly required to implement measures that target at-risk populations to prevent noncommunicable diseases. In this review we lay out what governments should be doing to prevent diabetes throughout the life course. The following four target groups were used to structure the specific recommendations: (1) pregnant women and young families, (2) children and adolescents, (3) working age population, and (4) the elderly. The evidence to date supports the effectiveness of some known government policy measures, such as sugar taxes and regulatory measures in the (pre-)school setting for children and adolescents. Many of these appear to be more effective if they are part of a bundle of strategies and if they are supplemented by communication strategies. Although there is a current focus on strategies that target the individual, governments can make use of evidence-based population-level prevention strategies. More research and continuous evaluation of the overall and subgroup-specific effectiveness of policy strategies using high-quality longitudinal studies are needed.

Evaluation and refinement of the PRESTARt tool for identifying 12-14 year olds at high lifetime risk of developing type 2 diabetes compared to a clinicians assessment of risk: a cross-sectional study.

BACKGROUND: Traditionally Type 2 Diabetes Mellitus (T2DM) was associated with older age, but is now being increasingly diagnosed in younger populations due to the increasing prevalence of obesity and inactivity. We aimed to evaluate whether a tool developed for community use to identify adolescents at high lifetime risk of developing T2DM agreed with a risk assessment conducted by a clinician using data collected from five European countries. We also assessed whether the tool could be simplified. METHODS: To evaluate the tool we collected data from 636 adolescents aged 12-14 years from five European countries. Each participant's data were then assessed by two clinicians independently, who judged each participant to be at either low or high risk of developing T2DM in their lifetime. This was used as the gold standard to which the tool was evaluated and refined. RESULTS: The refined tool categorised adolescents at high risk if they were overweight/obese and had at least one other risk factor (High waist circumference, family history of diabetes, parental obesity, not breast fed, high sugar intake, high screen time, low physical activity and low fruit and vegetable intake). Of those found to be at high risk by the clinicians, 93% were also deemed high risk by the tool. The specificity shows that 67% of those deemed at low risk by the clinicians were also found to be a low risk by the tool. CONCLUSIONS: We have evaluated a tool for identifying adolescents with risk factors associated with the development of T2DM in the future. Future work to externally validate the tool using prospective data including T2DM incidence is required.

Cue reactivity, habituation, and eating in the absence of hunger in children with loss of control eating and attention-deficit/hyperactivity disorder.

OBJECTIVE: Childhood loss of control (LOC) eating and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid conditions and present with disordered eating behaviors, such as overeating. This study sought to delineate shared and specific abnormalities in physiological, cognitive-motivational, and behavioral components of food-specific impulsivity in children with LOC eating and ADHD. Specifically, children's reactivity and habituation to food and eating in the absence of hunger were examined. METHODS: Within this community-based study, four groups of 8-13-year-old children with LOC eating (n = 24), ADHD (n = 32), comorbid LOC eating/ADHD (n = 9), and matched controls (n = 34) received a standard laboratory test meal to establish satiety and were then exposed to their favorite snack food in a cue exposure/reactivity trial, while salivation and desire to eat were repeatedly assessed. Subsequently, they were offered a variety of snack foods ad libitum. RESULTS: Children with LOC eating, ADHD, and LOC/ADHD did not differ from controls in salivary reactivity and habituation to food cues. Children with LOC eating and ADHD showed greater cue reactivity of the desire to eat than controls, but groups did not differ in its longer-term increments. At free access, only children with LOC/ADHD consumed significantly more energy than controls. Longer-term increments of desire to eat predicted greater energy intake beyond LOC/ADHD group status. DISCUSSION: Desire to eat among children with comorbid LOC eating and ADHD was associated with overeating in the absence of hunger, which may contribute to excess weight gain. Delineation of the specific features of childhood LOC eating versus ADHD warrants further study.

[Current literature overview on the therapy of obesity in children and adolescents]. / Aktuelle Literaturübersicht zur Therapie der Adipositas bei Kindern und Jugendlichen.

BACKGROUND: Obesity is a chronic disease due to the comorbidity associated with it and the need for long-term medical care. Therapeutic intervention is possible at every stage of pathophysiology. AIM: The aim of the study is to demonstrate the effect of multimodal lifestyle interventions not only on the BMI/BMI-SDS, but also on (secondary) outcomes such as comorbidities, quality of life as well as the nutritional and movement behavior. MATERIALS AND METHODS: The literature database PubMed has been searched for internationally clinical studies on lifestyle interventions among 0 to 18-year-olds with overweight and obesity in the period from 01/01/2009 to 01/01/2016. RESULTS: 64 publications with data from 55 studies were included in this overview. Through multimodal lifestyle interventions, many improvements have been achieved in the fields of comorbidity, quality of life, diet and exercise. DISCUSSION: The use of obesity therapy goes far beyond a weight reduction, which is why other parameters should be regularly recorded as therapeutic targets. Thus the improvement of comorbidities, the quality of life as well as the movement and nutritional behavior for a long-term healthy lifestyle are at least as important and reduce the risk of regain after initial weight reduction.

[Electronic media in obesity prevention in childhood and adolescence]. / Elektronische Medien in der Adipositas-Prävention bei Kindern und Jugendlichen.

BACKGROUND: The increasing prevalence of childhood obesity is - amongst other factors - due to changed leisure time habits with decreased physical activity and increased media consumption. However, electronic media such as tablets and smartphones might also provide a novel intervention approach to prevent obesity in childhood and adolescence. OBJECTIVES: A summary of interventions applying electronic media to prevent childhood obesity is provided to investigate short term effects as well as long term results of these interventions. METHODS: A systematic literature search was performed in PubMed/Web of Science to identify randomized and/or controlled studies that have investigated the efficacy of electronic media for obesity prevention below the age of 18. RESULTS: A total of 909 studies were identified, and 88 studies were included in the analysis. Active video games did increase physical activity compared to inactive games when applied within a peer group. Interventions via telephone had positive effects on certain lifestyle-relevant behaviours. Interventions via mobile were shown to decrease dropout rates by sending regular SMS messages. To date, interventions via smartphones are scarce for adolescents; however, they might improve cardiorespiratory fitness. The results from internet-based interventions showed a trend towards positive effects on lifestyle-relevant behaviors. The combination of different electronic media did not show superior results compared to interventions with only one medium. Interventions via TV, DVD or video-based interventions may increase physical activity when offered as an incentive, however, effects on weight status were not observed. DISCUSSION: Children and adolescents currently grow up in a technology- and media-rich society with computers, tablets, smartphones, etc. used daily. Thus, interventions applying electronic media to prevent childhood obesity are contemporary. Available studies applying electronic media are however heterogeneous in terms of applied medium and duration. Positive effects on body composition were not observed, but only on certain lifestyle-relevant behaviours. In addition, these effects could only be seen in the short term. Follow-up data are currently scarce.

Changes in Lifestyle and Body Weight in Children and Adolescents during the COVID-19 Pandemic: A Representative Survey of Parents in Germany.

INTRODUCTION: The public restrictions taken during the COVID-19 pandemic have substantially affected lifestyle and health behavior of children and adolescents. In Germany, little is known how these changes influenced daily life in families with children and adolescents. METHODS: A cross-sectional survey was performed in April/May 2022 across Germany, similar to a survey performed in 2020. Parents (N = 1,004, 20-65 years) with at least one child aged 3-17 years filled in an online questionnaire released by the Forsa Institute for Social Research and Statistical Analysis. Fifteen questions related to eating habits, dietary patterns, physical activity, media consumption, fitness, mental health, and body weight were included, and standard socioeconomic parameters were assessed. RESULTS: Parents' answers indicated that there was a parental self-reported weight gain in every sixth child since the beginning of the COVID-19 pandemic. This was most obvious in children from families with lower household income and preexisting overweight. Parents also reported that lifestyle patterns had worsened: 70% reported an increase of media consumption during leisure time, 44% a decrease in daily physical activity, and 16% the worsening of dietary habits (e.g., 27% stated to eat more cake and sweets). Children aged 10-12 years were most severely affected. CONCLUSION: Negative health effects related to the COVID-19 pandemic are predominantly observed in children 10-12 years of age and in children from families with low household income, suggesting a worsening social disparity. Political action is urgently needed to tackle the adverse consequences of the COVID-19 pandemic on childhood lifestyle and health.

Uric acid and gamma-glutamyl-transferase in children and adolescents with obesity: Association to anthropometric measures and cardiometabolic risk markers depending on pubertal stage, sex, degree of weight loss and type of patient care: Evaluation of the adiposity patient follow-up registry.

OBJECTIVES: Associations between body mass index (BMI)- standard deviation score (SDS)/waist-to-height ratio (WHtR) were studied with (i) serum uric acid (sUA)/gamma-glutamyl-transferase (GGT) and (ii) cardiometabolic risk markers in children with obesity, considering sex, pubertal development, and degree of weight loss/type of patient care. METHODS: 102 936 children from the Adiposity-Follow-up registry (APV; 47% boys) were included. Associations were analysed between sUA/GGT and anthropometrics, transaminases, lipids, fasting insulin (FI), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides to HDL-cholesterol (TG/HDL)-ratio. Follow-up analyses (3-24 months after baseline) considered a BMI-SDS reduction ≥0.2 (n = 11 096) or ≥0.5 (n = 3728). Partialized correlation analyses for sex and BMI-SDS were performed, taking pubertal development into consideration. RESULTS: At baseline, BMI-SDS showed the strongest correlations to sUA (r = 0.35; n = 26 529), HOMA-IR/FI (r = 0.30; n = 5513 /n = 5880), TG/HDL-ratio (r = 0.23; n = 24 501), and WHtR to sUA (r = 0.32; n = 10 805), GGT (r = 0.34; n = 11 862) and Alanine-aminotransferase (ALAT) (r = 0.33; n = 11 821), with stronger correlations in boys (WHtR and GGT: r = 0.36, n = 5793) and prepubertal children (r = 0.36; n = 2216). GGT and sUA (after partializing effects of age, sex, BMI-SDS) showed a correlation to TG/HDL-ratio (r = 0.27; n = 24 501). Following a BMI-SDS reduction ≥0.2 or ≥0.5, GGT was most strongly related to Aspartate-aminotransferase (ASAT)/ ALAT, most evident in prepuberty and with increasing weight loss, and also to TG/HDL-ratio (r = 0.22; n = 1528). Prepubertal children showed strongest correlations between BMI-SDS/WHtR and GGT. ΔBMI-SDS was strongly correlated to ΔsUA (r = 0.30; n = 4160) and ΔGGT (r = 0.28; n = 3562), and ΔWHtR to ΔGGT (r = 0.28; n = 3562) (all p < 0.0001). CONCLUSION: Abdominal obesity may trigger hyperuricemia and hepatic involvement already in prepuberty. This may be stronger in infancy than anticipated to date. Even moderate weight loss has favourable effects on cardiometabolic risk profile and glucose homeostasis.

Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity.

OBJECTIVE: The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. METHODS: Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7-13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79-2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. RESULTS: A total of 36.3% of children and adolescents experienced "no BMIz loss." The largest subcluster (44.8%) achieved "moderate BMIz loss," with an average delta-BMIz of -0.23 (IQR: -0.33 to -0.14) at study end. A total of 18.9% had a "pronounced BMIz loss" up to -0.61 (IQR: -0.76 to -0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). CONCLUSIONS: These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success.

[Using simulated patients to test competency in child protection medicine in the third section of the medical examination]. / Einsatz von Simulationspersonen zur Prüfung von Handlungskompetenz im Bereich der Kinderschutzmedizin im Dritten Abschnitt der Ärztlichen Prüfung.

During the COVID-19 pandemic, the third section of the medical examination could be performed with simulation patients. Simulations enable standardized examinations of medical competency according to the educational objectives of the national learning objectives catalogue. The evaluation of student's medical response to child abuse and neglect seems to be an appropriate opportunity to increase attention of prospective physicians for potential child abuse. The presented case reports the simulation of a pediatric nonaccidental trauma.

Access to Healthcare for Children and Adolescents with a Chronic Health Condition during the COVID-19 Pandemic: First Results from the KICK-COVID Study in Germany.

This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0−10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1%, JIA 11.1%, obesity 20%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6%; obesity 13.1%; JIA 5%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany.

Diabetic ketoacidosis in pediatric patients with type 1- and type 2 diabetes during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic caused families to stay home and cancel everyday activities. Hospital admissions decreased, affecting changes in diagnoses and management of chronic disease in children. AIMS: We analyzed how the first lockdown influenced clinical presentation and manifestation of children with diabetes mellitus (DM) in a German University Hospital. METHODS: During March 15th and October 11th 2020, data on general patient information, clinical symptoms and on lab results related to diabetic ketoacidosis (DKA) were analyzed in children (0-18 years) who presented with new onset of DM or poor metabolic control of known DM. All data including frequency and severity of DKA were compared to data from patients who presented in 2019. RESULTS: Data from 125 participants with DM were evaluated (2020: n = 52; 2019: n = 73). In 2020, twelve patients (23.1%) were diagnosed with new onset DM, two of them with type2 diabetes, and 66.7% presented with DKA including both patients T2DM. In 2019, 24.5% of patients had new onset DM, and 50% of them presented with DKA. In 2020, patients with new onset DM were younger, presented with more severe symptoms of DKA and had to stay longer in hospital compared to 2019. In 2020, six children (50%) with new onset DM were <6 years, whereas in 2019 most children with new onset DM were adolescents (n = 7, 38.9%). CONCLUSION: COVID-19 lockdown aggravated complications of diabetes onset and therapy management, including severity and frequency of DKA. It underlines the need of health education for early DKA diagnosis to early identify children at risk.

Update on Metabolic Bariatric Surgery for Morbidly Obese Adolescents.

Despite worldwide public attention and intense medical efforts, the prevalence of severe morbid obesity in children and adolescents is still rising. Similar to adults, excess adipose tissue triggers multiple immunological and metabolic pathways leading to serious co-morbidities such as impaired glucose tolerance or even type 2 diabetes (T2D), dyslipidemia, arterial hypertension, non-alcoholic fatty liver disease, and hyperuricemia. The management of severe childhood obesity requires a life-long multidisciplinary approach with a combination of lifestyle changes, nutrition, and medications. Standardized life-style intervention programs remain the first-line treatment for morbid obese children and adolescents, but unfortunately reveal limited long-term success. In such cases, metabolic bariatric surgery (MBS) has evolved from being a controversial issue to being included in distinct recommendations. According to the American Society for Metabolic and Bariatric Surgery (ASMBS) Pediatric Committee, indications for bariatric surgery in adolescence must follow very strict criteria. Adolescents with class II obesity (BMI > 120% of the 95th percentile) and a diagnosed co-morbidity or with class III obesity (BMI ≥ 140% of the 95th percentile) should be considered for MBS. These interventions represent high-risk operations, and adolescents should be treated in specialized, multidisciplinary high-volume obesity centers with long-term follow-up programs. The Roux-en-Y gastric bypass (RYGB) remains the gold standard of all malabsorptive procedures. Laparoscopic sleeve gastrectomy (LSG), which the authors pioneered as a stand-alone procedure in morbidly obese adolescents in 2008, has become the most commonly performed operation in morbidly obese adolescents at present. Recent literature proves that MBS is safe and effective in morbidly obese adolescents. Mid-term data have revealed significant improvement or even resolution of major co-morbidities. Thus, MBS for the treatment of morbidly obese adolescents has evolved from being a controversial issue to being included in distinct recommendations by several medical societies as a therapeutic strategy to reduce severe co-morbidities potentially causing end-organ damage in adulthood.

Development of an Interactive Lifestyle Programme for Adolescents at Risk of Developing Type 2 Diabetes: PRE-STARt.

BACKGROUND: Type 2 diabetes (T2D) is increasing in young people. Reporting on the processes used when developing prevention interventions is needed. We present the development of a family-based interactive lifestyle intervention for adolescents with risk factors for T2D in the future. METHOD: A multidisciplinary team in the UK site led the intervention development process with sites in Portugal, Greece, Germany and Spain. Potential programme topics and underpinning theory were gathered from literature and stakeholders. A theoretical framework based on self-efficacy theory and the COM-B (capability, opportunity, motivation, behaviour) model was developed. Sessions and supporting resources were developed and refined via two iterative cycles of session and resource piloting, feedback, reflection and refinement. Decision on delivery and content were made by stakeholders (young people, teachers, parents, paediatricians) and all sites. Materials were translated to local languages. Site-specific adaptations to the language, content and supporting resources were made. RESULTS: The "PRE-STARt" programme is eight 90-min interactive sessions with supporting curriculum and resources. Iterative development work provided valuable feedback on programme content and delivery. CONCLUSION: Reporting on the intervention development process, which includes stakeholder input, could yield a flexible approach for use in this emerging 'at risk' groups and their families.

Childhood Obesity and Cancer Risk in Adulthood.

PURPOSE OF REVIEW: The purpose of this review is to summarize our current understanding of the association between childhood obesity and cancer risk later in life. RECENT FINDINGS: Adipose tissue secrets a variety of adipocytokines, and expression and/or secretion rate of most of them seems to be increased or dysregulated in obesity. In addition, obesity leads to increased secretion of proinflammatory cytokines such as interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), which promotes an infiltration of inflammatory immune cells into adipose tissue. This process may facilitate a state of "subclinical inflammation" (metaflammation) and may lead to the development of the metabolic syndrome (MetS), starting as early as during childhood. In addition, several oncogenes have been linked to inflammation and cancer development via different pathways, and several types of tumors need an inflammatory environment before a malignant change occurs. An inflammatory environment seems to promote the proliferation and survival of malignant cells as well as angiogenesis. Natural killer (NK) cells play an important role in this process, as they are able to kill transformed cells without prior sensitization and coordinate subsequent immune responses by producing distinct cytokines, thus providing antitumor immunity. First studies in children have suggested that NK cells from obese children are activated, metabolically stressed, and functionally deficient. This may lead to a suppression of antitumor immunity as early as during childhood, probably many years before the development of cancer. Epidemiological studies have shown a strong association between higher body mass index (BMI) during childhood and adolescence and increased risk for several malignancies in adulthood, including leukemia, Hodgkin's disease, colorectal cancer, and breast cancer. Underlying mechanisms are not completely understood, but several adipocytokines and inflammatory markers including NK cells seem to be "key players" in this process.

A Comprehensive Cohort Analysis Comparing Growth and GH Therapy Response in IGF1R Mutation Carriers and SGA Children.

CONTEXT: IGF1 receptor mutations (IGF1RM) are rare; however, patients exhibit pronounced growth retardation without catch-up. Although several case reports exist, a comprehensive statistical analysis investigating growth profile and benefit of recombinant human growth hormone (rhGH) treatment is still missing. OBJECTIVE AND METHODS: Here, we compared IGF1RM carriers (n = 23) retrospectively regarding birth parameters, growth response to rhGH therapy, near final height, and glucose/insulin homeostasis to treated children born small for gestational age (SGA) (n = 34). Additionally, health profiles of adult IGF1RM carriers were surveyed by a questionnaire. RESULTS: IGF1RM carriers were significantly smaller at rhGH initiation and had a diminished first-year response compared to SGA children (Δ height standard deviation score: 0.29 vs. 0.65), resulting in a lower growth response under therapy. Interestingly, the number of poor therapy responders was three times higher for IGF1RM carriers than for SGA patients (53 % vs. 17 %). However, most IGF1RM good responders showed catch-up growth to the levels of SGA patients. Moreover, we observed no differences in homeostasis model assessment of insulin resistance before treatment, but during treatment insulin resistance was significantly increased in IGF1RM carriers compared to SGA children. Analyses in adult mutation carriers indicated no increased occurrence of comorbidities later in life compared to SGA controls. CONCLUSION: In summary, IGF1RM carriers showed a more pronounced growth retardation and lower response to rhGH therapy compared to non-mutation carriers, with high individual variability. Therefore, a critical reevaluation of success should be performed periodically. In adulthood, we could not observe a significant influence of IGF1RM on metabolism and health of carriers.

Metabolic Syndrome in Children and Adolescents: Diagnostic Criteria, Therapeutic Options and Perspectives.

PURPOSE OF REVIEW: This review summarizes our current understanding of the metabolic syndrome (MetS) in children and adolescents. Special emphasis is given towards diagnostic criteria and therapeutic options. RECENT FINDINGS: Consistent diagnostic criteria to define MetS in childhood and adolescence are not available to date. There is common agreement that the main features defining MetS include (1) disturbed glucose metabolism, (2) arterial hypertension, (3) dyslipidemia, and (4) abdominal obesity. However, settings of cut-off values are still heterogeneous in the pediatric population. Additional features that may define cardiometabolic risk, such as non-alcoholic fatty liver disease (NAFDL) or hyperuricemia, are not considered to date. Prevalence of childhood obesity has more than doubled since 1980, and 6-39% of obese children and adolescents already present with MetS, depending on the definition applied. There is common agreement that a consistent definition of MetS is urgently needed for children to identify those at risk as early as possible. Such definition criteria should consider age, gender, pubertal stage, or ethnicity. Additional features such as NAFDL or hyperuricemia should also be included in MetS criteria. Lifestyle modification is still the main basis to prevent or treat childhood obesity and MetS, as other therapeutic options (pharmacotherapy, bariatric surgery) are not available or not recommended for the majority of affected youngster.

Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood.

Prevalence of childhood obesity has worldwide more than doubled since 1980. Underlying factors are complex and are far from completely understood. Strategies to prevent childhood obesity have mainly focused on behavioral intervention; and obesity therapy was mainly based on lifestyle modification to date. However, effects for both have been quite limited so far and no country has succeeded in fighting the obesity epidemy we are facing. Normalization of body weight before onset of puberty is crucial for several reasons: First, obese children and adolescents frequently stay obese until adulthood. Second, obesity during adolescence is significantly associated with increased risk for cardiovascular and metabolic disease such as type 2 diabetes in adulthood. And third, recent data have shown a strong association between higher body mass index (BMI) during adolescence and increased risk for several malignancies such as leukemia, Hodgkin's disease, colorectal cancer, breast cancer and others in adulthood. This review summarizes our current understanding of epidemiology, underlying factors, concomitant disease, as well as available intervention strategies and gives an overview of what has been reached so far and what measures should be undertaken to counteract the obesogenic environment.