Bariatric surgery in monogenic and syndromic forms of obesity

Currently, no topic is more controversial in bariatric surgery than performing these procedures on children with monogenic and syndromic forms of obesity. The medical community and the caregivers of those patients are struggling to find a solution that can alleviate their suffering and save their life. In all forms of obesity, dieting and physical activity do not result in significant weight loss and is associated with a high rate of weight regain. Additionally, effective medical therapy is not available yet. While there is significant debate about the risks and benefits of bariatric surgery in the adolescent population, there is an increasing number of studies that demonstrate the success of this option for the appropriate patients. Similarly, our experience demonstrated the same success not only in normal children and adolescents but also in those with monogenic and syndromic form of obesity.     

An overview of mongenic and syndromic obesities in humans

Obesity is increasing in prevalence in the United States with over 65% of adults considered overweight and 16% of children with BMI > 95 percentile. The heritability of obesity is estimated between 40% and 70%, but the genetics of obesity for most individuals are complex and involve the interaction of multiple genes and environment. There are however several syndromic and non-syndromic forms of obesity that are monogenic and oligogenic that provide insight into the underlying molecular control of food intake and the neural networks that control ingestive behavior and satiety to regulate body weight and which may interact with treatment exposures to produce or exacerbate obesity in childhood cancer survivors.     

Paediatric obesities: from childhood to adolescence

Obesity, as in every western country, is currently the most prevalent chronic disease in childhood in Spain. This has led to obesity being one of the most common consultations in general paediatrics and, particularly, in paediatric endocrinology. Furthermore, obesity associated comorbidities are increasing in prevalence in children and adolescents. It is widely accepted that this increase in the prevalence of obesity is derived from an imbalance between energy intake and expenditure, associated to the lifestyle in western countries. However, there is increasing evidence of the role of individual and familial genetic background in the risk of developing obesity. The pathophysiological basis of the mechanisms responsible for the control of appetite and energy expenditure are being discovered on the basis of the increasing known cases of human monogenic, syndromic and endocrine obesity. Thus it is no longer appropriate to talk about obesity but rather about ?obesities?, as their pathophysiological bases differ and they require different diagnostic and management approaches. In 2011, the paediatrician must be aware of this issue and focus the clinical history and physical examination towards these specific clinical sign and symptoms, to better manage the available diagnostic and therapeutic resources when faced with a child with obesity.     

The rare syndromic forms of monogenic diabetes in childhood

The most frequent form of diabetes in the childhood is type 1 diabetes. Moreover, the rare forms of diabetes have been also identified in children. Besides of neonatal diabetes caused by the mutations in KCNJ11, SUR1 and GCK genes, other forms of monogenic diabetes are associated with different chronic disorders. These rare forms of syndromic diabetes are related to mutations in genes which lead to Wolfram syndrome, Alstr?m syndrome, Wolcott-Rallison syndrome or Roger's/TRMA syndrome. In this paper we discuss the clinical features of rare syndromic forms of monogenic diabetes, which gave suggestions on pathogenic mechanism of the diagnosed diabetes in childhood. This may be helpful for appropriate classification of the epidemiological, clinical and genetic data. It may be useful in the future to the form of the Polish National Survey of rare syndromic forms of monogenic diabetes in childhood.     

Megaloblastic anaemia in infancy or early childhood and diabetes as leading symptoms of the TRMA syndrome

Diabetes mellitus may occur in children and adolescents as an independent disease, most frequently as autoimmune type 1 diabetes, or can coexist with other abnormalities. If diabetes coincides with other disorders occurring sequentially, a syndromic form of monogenic diabetes should be suspected. Thiamine-responsive megaloblastic anaemia (TRMA) syndrome is an example of a rare form of monogenic diabetes coexisting with anaemia and deafness. In the paper, we discuss clinical features and treatment of TRMA syndrome - a unique syndromic form of vitamin-dependent monogenic diabetes. The review might be useful in establishing a prompt diagnosis and initiating optimal management in children and adolescents with the disease.     

Body fat ratios in urban Chinese children

OBJECTIVE: As obesity has been increasing in China, the present study examined the body composition of children to assess their fatness. STUDY DESIGN: A total of 532 healthy schoolchildren who lived in central Beijing were examined. Skinfold thicknesses, hip and waist circumferences, and body fat percentage were measured, as well as height and weight. RESULTS: The prevalence of overweight (Body Mass Index (BMI) >or= 95% for age and sex of Chinese children) was 27.7% in boys and 14.2% in girls (chi-squared; P = 0.0001). The percentages of body fat (BF%), waist/hip ratios and skinfold thicknesses ratios (subscapular/triceps) in overweight children were significantly higher than those in non-overweight children (Mann-Whitney U-test). The BF% of non-overweight boys was significantly higher than that of non-overweight girls. CONCLUSION: Urban Chinese overweight children have high BF% with adverse fat distribution. They may have high risk of atherogeniety. Boys in the non-overweight category may have higher fat accumulation than predicted by BMI. The establishment of an intervention program for childhood obesity is strongly recommended.     

Definition of obesity in childhood: criteria and limits

A rigorous scientific definition of obesity in childhood is not yet available: in fact, there is not agreement among researchers on the adiposity index to use and on the best cut-off to define overweight and obesity. In this review, the reference methods for the diagnosis of childhood obesity in the clinical practice in Italy are reported. All the statements are based on evidences of the literature and obtained the consensus of the pediatricians of the Study Group on Obesity of the Italian Society of Pediatric Diabetology and Endocrinology. Obesity is caused by an excess of body fat. The methods more frequently used to measure body fat are the measure of subcutaneous skinfold thickness, bioimpedence assessment and DXA. The measure of skinfolds is preferable in the clinical setting because it is easy to use and cheap, although reproducibility is modest. Triceps skinfold is commonly used to define obesity: children with triceps higher than the 85(th) centile for age and gender, using Tanner's tables, are obese. An estimation of fat mass obtained, for instance, with skinfolds is always suggested in addition to the measure of weight and height. It is possible to define a child as obese calculating the ratio between weight (kg) and height squared (m). This ratio is an index, called body mass index (BMI), which is strictly associated to the level of adiposity in children, reproducible and valid. The BMI was recently proposed as the reference index for the diagnosis of childhood obesity at the international level. The use of the centiles of BMI may offer useful information on the changes of weight excess, simplifying the follow-up of the patient and the sensitivity to treatment. The cut-off limits of BMI to define overweight or obesity are still debated. However, in agreement with Cole et al., the choice to use the BMI cut-offs centiles passing through the adult BMI cut-off of 30, is reasonable. However, it is always preferable to use population specific BMI reference tables.     

Effect of weight loss on body fat distribution in obese children

The intra-abdominal visceral fat to subcutaneous fat ratio (V/S ratio) has been reported to be strongly related to disorders of glucose and lipid metabolism, and hypertension. It is a matter of concern as to whether weight loss causes an improvement of the V/S ratio or not in obese children. Changes in body fat distribution during weight loss in 23 obese children were quantified by weight, bioelectrical impedance analysis (BIA) and computed tomography (CT scan of the abdomen). Twenty-three patients were divided into two groups; six were in the inpatient group and 17 were in the outpatient group. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were significantly higher in the inpatient group than in the outpatient group before weight loss. Whereas the V/S ratio was almost equal between the two groups before weight loss. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were found to decrease significantly during weight loss in the two groups. The V/S ratio of the outpatient group did not change after weight loss. In contrast, the V/S ratio of the inpatient group decreased significantly during weight loss. These preliminary findings suggest that a large amount of body fat and a high obesity rate are not always accompanied by a high V/S ratio in obese children. The fat pattern changes during weight loss with strict dietary therapy and therapeutic exercise. A larger sample of obese children should be studied to test this conjecture.     

Genetische Ursachen von Fieberkrämpfen

Genetic factors play an important role in the etiology of febrile seizures. In recent years, genes have been identified for several monogenic epilepsies in which febrile seizures are part of the clinical phenotype. Examples of epilepsies in which syndromic febrile seizures occur are generalized epilepsy with febrile seizures plus (GEFS⁺) and the Dravet syndrome. In temporal lobe epilepsy a genetic association between a history of febrile seizures and epilepsy is also being discussed. However, most febrile seizures have a polygenic not a monogenic background and are caused by a combination of several different genetic factors with non-genetic causes.     

The social patterning of fat and lean mass in a contemporary cohort of children.

Studies of the social patterning of obesity in children using body mass index have reported inconsistent results. We explored the association of social class with fat mass and lean mass in a contemporary cohort of children measured using dual energy X-ray absorptiometry. We observed a clear social gradient of fat mass (with children of higher social class having a lower fat mass), but no gradient in lean mass or trunk fat mass. Our data show that inequalities in adiposity are present in primary school children and suggest that social inequalities in childhood obesity may have been underestimated in previous studies.     

Significance of the atherosclerogenic index and body fat in children as markers for future, potential coronary heart disease

BACKGROUND: The purpose of this study is to establish a simple marker in children for future, potential risks of coronary heart disease. METHODS: We measured serum total cholesterol (TC) and triglyceride (TG) by enzymatic methods, high-density lipoprotein cholesterol (HDLC) by the dextran sulfate-magnesium method and estimated body fat by the new impedance method in 1289 children (651 boys and 638 girls) in the fourth grade (9 or 10 years old) to obtain the atherosclerogenic index (AI). We also investigated the children's lifestyle. RESULTS: The probability of an AI score of 3 or more was significantly higher in children with an estimated 23-25% body fat than in those with body fat less than 17%. Moreover, the odds ratio increased along with an increase in the percentage of body fat. When body fat was estimated as being greater than 29%, the odds ratio was 11-fold higher than those with body fat less than 17%. When body fat was greater than 23%, the children's physical activity, as assessed by the questionnaire, was found to be poorer than those with lower body fat. Levels of TC and TG were significantly higher and that of HDLC was lower in those with less body fat. CONCLUSIONS: The AI is a useful indicator of obesity in children. The combination of AI and percentage body fat is a good indicator for evaluating children who would be at a greater risk of obesity, hyperlipidemia, unhealthy eating habits and inadequate physical activity. The hypothetical risk levels for future coronary heart disease are an AI score of > or = 3 and percentage body fat > or = 23% in Japanese children.     

Body Size, Parental Appraisal, and Self-Esteem in Blind Children

This study of self-esteem, body size, and parental views in 9–11–year-old blind children found positive views about self-presentation with no sex or weight differences. Lower self-esteem emerged in children who thought they were judged by parents as too thin but being fat. being appraised as fat, or believing they are thought of as fat by parents, showed mi effect on self-esteem. Their responses to questions about the causes, characteristics, and psychosocial functioning of obesity suggest an innate desire and possible need for a more robust stature, a bigger presence, and a feeling of weight which appeared to supercede any acquired negative attitudes to fatness.     

Obesity genes: implication in childhood obesity

Overweight and obesity prevalence has dramatically increased during the last decade and reached epidemic dimensions. By 2030 it is expected that there will be 2.16 billion overweight individuals with 1.12 billion adults predicted to be clinically obese. Obesity is caused by both genetic and non-genetic factors. BMI as a common measure of obesity is a highly heritable trait with heritability estimates of ～0.7 for both adults and children. Mutations in a few genes such as LEPR and MC4R identified by molecular genetic analysis in children are known to be involved in rare monogenic severe obesity. Their identification opened important insights in fundamental pathways, in particular the leptin-melanocortin pathway, involved in control of appetite and energy metabolism. However, the polygenic basis of common obesity with many common variants conferring each modest risk to the phenotype is still one of the major challenges in genetics of obesity. Driven by the availability of genome wide association (GWAS) technology enabling analysis of millions of markers in thousands of individuals, multiple polymorphisms/genes have been identified in the last 5 years. With common genetic variants in genes such as FTO (fat mass and obesity-associated gene) a great number of additional susceptibility variants have been identified altogether still accounting for a small percentage of the overall risk for obesity. This review outlines the progress of research in genetics of obesity during recent years in adults and children.     

Assessment of obesity in early childhood

Abstract Measures of physical development were gathered at birth and at ages 3, 5 and 7 years on a sample of over 800 children as part of a multidisciplinary development study. Direct measures of obesity (skinfolds, visual estimate and calculated fat body mass) were correlated with a range of indices based on height and weight (Eid, Ponderal, Quetelet's or Body Mass Index [BMI] and a modified BMI) to determine a valid and reliable index of obesity. Quetelet's or BMI (weight divided by height squared) was found to be the best index of obesity, correlating between 0.88 and 0.96 with percentage fat body mass at ages 5 and 7 years. The BMI also correlated consistently higher indices with all direct measures of body fat than did the other indices. The results indicate that in children, as in adults, BMI can be used to assess obesity simply. It has several advantages, being easy to collect, non-invasive, objective, and requires no special equipment or highly trained personnel. Finally, the BMI, involving as it does only height and weight, can be used to assess obesity retrospectively in the numerous populations which have records of height and weight.     

Assessment of obesity in early childhood

Measures of physical development were gathered at birth and at ages 3, 5 and 7 years on a sample of over 800 children as part of a multidisciplinary development study. Direct measures of obesity (skinfolds, visual estimate and calculated fat body mass) were correlated with a range of indices based on height and weight (Eid, Ponderal, Quetelet's or Body Mass Index [BMI] and a modified BMI) to determine a valid and reliable index of obesity. Quetelet's or BMI (weight divided by height squared) was found to be the best index of obesity, correlating between 0.88 and 0.96 with percentage fat body mass at ages 5 and 7 years. The BMI also correlated consistently higher indices with all direct measures of body fat than did the other indices. The results indicate that in children, as in adults, BMI can be used to assess obesity simply. It has several advantages, being easy to collect, non-invasive, objective, and requires no special equipment or highly trained personnel. Finally, the BMI, involving as it does only height and weight, can be used to assess obesity retrospectively in the numerous populations which have records of height and weight.     

Link between body fat and the timing of puberty

Several recent studies suggest that the timing of the onset of puberty in girls has become earlier over the past 30 years, and there is strong evidence that the increasing rates of obesity in children over the same time period is a major factor. This article reviews studies from the United States that examined the age of menarche and the age of onset of breast development and pubic hair as a function of body mass index, which is a good surrogate measure of body fat. These studies are nearly all cross-sectional, so many questions remain unanswered. However, at least several studies show that girls who have relatively higher body mass index are more likely to have earlier menses, as well as a relationship between body mass index and other measures of pubertal onset. The evidence published to date suggests that obesity may be causally related to earlier puberty in girls rather than that earlier puberty causes an increase in body fat. In contrast, few studies have found a link between body fat and earlier puberty in boys. A growing body of evidence from both rodent and human studies suggests that leptin may be the critical link between body fat and earlier puberty. Leptin-deficient mice and humans fail to enter puberty unless leptin is administered, and rodent studies indicate that very low levels of leptin stimulate gonadotropin secretion both at the hypothalamic and the pituitary level. Current evidence indicates that leptin appears to play a permissive role rather than act as the critical metabolic signal initiating puberty. The linkage between body fat and the reproductive axis in girls may have evolved in mammals as a mechanism for ensuring that pregnancy will not occur unless there are adequate fat stores to sustain both the mother and the growing fetus.     

应用传统超声和多普勒组织显像检测单纯性肥胖小儿左心结构和左心功能

目的 明确儿童期单纯性肥胖对心血管系统的影响。方法 应用传统超声和彩色多普勒组织显像技术(DTI)全面检测63例7-14岁中重度单纯性肥胖儿童及63例正常体重对照儿童的左心解剖和功能,并分析其与肥胖程度的关系。结果 ①肥胖组左室舒张内径、室间隔和左室后壁厚度、左室心肌重量(LVM)显著增加(P<0.01),而LVM指数(LVMI,LVM／体表面积)无明显变化(P＞0.05);搏血指数和心脏指数显著降低(P＜0.01＝;二尖瓣环血流速度A峰,E／A,左室后壁舒张早期内外膜运动速度差值(DME),二尖瓣环舒张早期运动速度(DeV),舒张晚期运动速度(DaV),舒张早晚期运动速度比(DeV／aV)均有显著改变(P<0.01)。②LVM与体重和皮脂厚度均有显著相关性(P<0.05);女性肥胖儿童的体重和皮脂厚度与DmeVG,DaV,DeV／aV均有显著相关性(P<0.05);男性肥胖儿童体重与DaV,皮脂厚度与DaV,DeV／aV有明显相关性(P<0.05);腰臀比与左室肥大和左心功能减低均无相关性(P>0.05)。③LVM与DaV,DeV／aV有明显相关性（P<0.05)。结论 早期的单纯肥胖即出现了左室肥厚和左心功能减低,并与体重和皮脂厚度密切相关。与成人肥胖症不同,肥胖儿童的LVMI无明显改变。腰臀比与心血管系统受累无明显相关性,因儿童期肥胖以周围型肥胖为主。     

Is obesity related to the lung function of non-asthmatic children?

Overweight and obesity are highly prevalent in developed and developing countries among children and adolescents. During the last two decades, it became evident that excess weight is adversely related to respiratory health in childhood and adolescence mainly in terms of asthma occurrence. Additionally, there is a mounting body of evidence that overweight/obesity may also affect lung function in non-asthmatic subjects. The aim of this review was to present and discuss the studies that investigated this issue in non-asthmatic children and adolescents. Only a few studies have evaluated the impact of excess weight on static volumes and their results point towards an inverse relationship between overweight/obesity and functional residual capacity. More studies have been conducted on the impact of excess weight on dynamic lung volumes with inconsistent, however, results. Nevertheless, a relatively consistent finding was that the ratio of forced expiratory volume in 1 s/forced vital capacity was significantly lower among overweight/obese children compared to their counterparts with normal weight. The underlying mechanisms of these observations have not been adequately elucidated but it is believed to result from complex interaction of mechanical, developmental, and metabolic causes. There is a need for more well-designed studies in order to clarify the impact of excess weight on lung function in non-asthmatic subjects, as well as to explore the contribution of factors such as duration and degree of obesity, and fat distribution. Despite the absence of conclusive data, there are still convincing evidence to be communicated to the children and their families as part of the arguments to encourage them to adopt a healthier lifestyle.     

From sleep duration to childhood obesity—what are the pathways?

Sleep duration has been identified as risk factor for obesity already in children. Besides investigating the role of fat mass (FM), this study addressed the question whether endocrine mechanisms act as intermediates in the association between sleep duration and overweight/obesity. Within the framework of the IDEFICS study, the present research was conducted in 609 German resident children aged 2-9 years with information on fasting insulin, C-reactive protein and cortisol levels next to anthropometric measurements and parental questionnaires. Emphasising methodological aspects, an age-specific measure of sleep duration was derived to account for alteration in sleep duration during childhood/period of growth. Multivariate linear regression and quantile regression models confirmed an inverse relationship between sleep duration and measures of overweight/obesity. The estimate for the association of sleep duration and body mass index (BMI) was approximately halved after adjustment for FM, but remained significant. The strength of this association was also markedly attenuated when adjusting for insulin mainly for the upper BMI quantiles (Q80, β =?-0.36 vs. β =?-0.26; Q95, β =?-0.87 vs. β =?-0.47). Adjustment for cortisol and CrP did not yield this attenuation. Conclusion: The inverse relationship between sleep duration and BMI is mainly explained by the association between sleep duration and FM. Insulin may explain part of this association, in particular at the upper tail of the BMI distribution.