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Query: UMLS:C0028754 (obesity)
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Prader-Willi syndrome (PWS), with a prevalence of 60:1.000.000, results from the loss of paternal chromosome 15, being 56% due to deletion, 24% due to uniparental maternal disomy, and 18% from methylation, an epigenetic phenomenon. The clinical picture begins with extreme muscular hypotonia, which makes it difficult to feed the child in the first year. As the hypotonia improves, usually in the first two years, around the 4th year of life, an insatiable appetite leads these children to an extreme obesity, with alveolar hypoventilation which endangers their lives. So, paradoxically, PWS threatens the lives of the patients, through inanition in a first phase and, afterwards, through excessive weight gain. The use of growth hormone (hrGH) in these children has a primary goal to change the body composition and improve the physical activity and the quality of life. On the other hand, many PWS patients are indeed GH deficient, and an improvement in the height SDS occurs with treatment. We have to be careful, however. When starting a PWS treatment with a patient on hrGH, a careful evaluation of sleep apnoea (polysomnography) as well as a careful examination of the airways is extremely mandatory, since the treatment may compromise the respiratory pattern of some patients.
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PMID:[Growth hormone usage in Prader-Willi syndrome]. 1879 90

Obesity can cause insulin resistance and cardiovascular and liver disease. The aim of this study was to analyze changes in laboratory values, body composition, and physical fitness before and after a one-year weight loss program with nutritional education, psychological care, and physical exercise. Twenty-two obese children (16 boys, 6 girls; median age 11.9 [range 7-15] years; BMI SDS +2.4 [1.6-3.1]) participated in the program. Outcome measures included liver enzymes, insulin resistance (HOMA), lipids, body composition, physical strength and endurance. All children had an inverse HOMA/body composition correlation; Group 1 (reduced BMI SDS after one year) had lower triglycerides, liver enzymes and improved body composition and fitness (p < 0.05). Group 2 (unchanged or increased BMI SDS) had worse body composition and increased endurance and strength of trunk extension (p < 0.05). Weight loss reduced risk factors for liver disease and improved insulin sensitivity. Body composition proved useful as a non-invasive indicator for insulin sensitivity.
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PMID:Changes in hepatic risk factors, metabolic variables, body composition, and physical fitness in obese children after a one-year weight loss program. 1892 77

It is controversial whether obesity in children is associated with earlier onset of puberty and advanced appearance of distinct parameters of pubertal development. To investigate the impact of obesity on markers of the onset and parameters representing stages of puberty, we analyzed auxological parameters and secondary sex characteristics in three representative cohorts of Caucasian children. Body weight, height, peak height velocity and pubertal stages were evaluated in two recent German cohorts (CrescNet and Leipzig Schoolchildren), and a historical Swiss cohort. According to body mass index (BMI), children were classified into three weight groups of lean, overweight, or normal weight with limits defined below -1.28 and above +1.28 BMI SDS. Peak height velocity (PHV) occurred significantly later in lean compared to normal weight children in the CrescNet and Swiss cohort, while there was no difference between obese and normal weight children. There was a trend towards acceleration of parameters of puberty onset and progression in obese children in all three cohorts. Height SDS was significantly higher in obese children compared to normal weight peers, but after completion of pubertal development it was similar in adolescents. The impact of overweight on the acceleration of puberty seems to be slightly stronger in boys. Once girls have reached a critical weight for entering the process of maturation, further increase in body weight does not seem to advance the onset of puberty.
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PMID:Impact of weight status on the onset and parameters of puberty: analysis of three representative cohorts from central Europe. 1892 74

Prader-Willi syndrome (PWS) is characterized by hypotonia, hypogonadism, obesity, and short stature. Neurobehavioral abnormalities, cognitive impairment, and sleep-related breathing disorders (SRBD) are common. In the general population associations between neurobehavioral and cognitive abnormalities and SRBD have been found. We investigated cognition, behavior, and SRBD in children with PWS. Thirty-one pre-pubertal PWS children were evaluated (5 with paternal deletion, 14 with maternal disomy, 4 with imprinting-center mutation, and in 8 the defect was not specified). Cognition was assessed by Wechsler scale subtests, and behavior by parent-questionnaires. Polysomnography was performed. Cognition, behavior, and associations with SRBD were evaluated. All cognitive subtests were significantly below O SDS, with the lowest median (interquartile range) scores for the Block design subtest (-2.7 SDS (-3.0 to -0.3)). In 60%, verbal subtests were less affected than performance subtests. Parents reported problem behavior related to "emotions/behavior not adapted to the social situation" and "insensitivity to social information." All children had SRBD, with an Apnea Hypopnea Index of 4.1/hr (2.6-7.9). One performance subtest score was significantly higher in children with better sleep efficiency, and daytime sleepiness was associated with more autistic-like social impairment. In contrast to our expectations, behavior was worse in children with better sleep-related breathing. In pre-pubertal PWS children, cognition is impaired. Neurobehavioral abnormalities are common, particularly autistic-like social impairment. Sleep efficiency was associated with better performance on one of the performance subtests, and neurobehavioral abnormalities were associated with daytime sleepiness. In contrast, we could not confirm a positive association of neurobehavioral abnormalities with SRBD in PWS.
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PMID:Cognition and behavior in pre-pubertal children with Prader-Willi syndrome and associations with sleep-related breathing disorders. 1900 9

Obesity in human was found mainly due to the poor transportation of leptin through brain-blood barrier (BBB), called as leptin resistance. To produce a leptin capable of penetrating BBB, we have added Tat-PTD(9) to the C terminal of leptin to construct a fusion protein. The fusion Tat-leptin and native leptin genes were synthesized by single-step insertion of a polymerase chain reaction and expressed in Escherichia coli BL21 (Rosseta). The expressing products were purified and renatured by Ni-NTA affinity chromatography, and identified by the molecular size in SDS-PAGE gel and by its immunoreactivity to specific antibody with Western-blotting assay. To bio-functionally evaluate the fusion protein, Balb/c mice fed with high-fat diet (HFD) were given Tat-leptin, leptin or saline for 19 days. The immunohistochemical staining showed the increases in positive stains for the leptin in the region of hypothalamus of the HFD mice with either Tat-leptin or leptin as compared to saline group, but the staining intensity and frequency in the group with Tat-leptin were stronger and higher than those in the group with leptin. Furthermore, the most efficiency in preventing the body-weight gain caused by HFD was found in Tat-leptin group among these three groups. These results suggest that Tat-modified leptin may become a great potential candidate for the prevention or therapy of obese patients.
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PMID:Tat-modified leptin is more accessible to hypothalamus through brain-blood barrier with a significant inhibition of body-weight gain in high-fat-diet fed mice. 1947 1

The spread of overweight and obesity is alarming in the face of metabolic syndrome development and its consequences. As obesity becomes a social norm, a lack of adequate attention seems to be noticed. In the development of obesity special attention is focused on preschool and pubertal periods, as they are considered as critical in the development of obesity and its persistence into adulthood. We have analyzed anthropological parameters of 302 overweight and obese children, patients of the Department of Pediatrics and Endocrinology between 2004-2007. Children were at the age from 1.5 y to 18.25 y. Overweight was diagnosed when BMI > or =1 SDS, obesity when BMI > or =2 SDS. 77% of boys and 86% of girls were obese. The mean value of BMI, expressed as SDS BMI, was +4.3 SDS (girls) and +4.5 SDS (boys) in children under 6 yrs, +3.03 SDS (girls) and +2.95 SDS (boys) in children between 6-14 yrs, +3.95 SDS (girls) and +4.08 (boys) in children above 14 yrs. The youngest group (i.e. under 6 yrs), although comparatively most obese, was sparse: 7% of all girls and 5.6% of all boys. The oldest group (i.e.above 14 yrs) was plentiful (45.6% of all girls and 27.8% of all boys) and comparatively very obese. Data of parents' weight status were completed in 56% of cases: 31.2% of mothers and 41.5% of fathers were overweight, 33.3% of mothers and 50.8% of fathers were obese. These observations can suggest that overweight and obesity can be underestimated and/or ignored/ disregarded in preschool and pubertal children. It seems to be alarming as these two periods of life are critical in the development of obesity. Special attention should be applied in the field of prevention of obesity, especially in younger children, and early identification of overweight small children and/ or children at risk of obesity.
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PMID:[Overweight and obesity in preschool children: an underestimated problem?]. 1948 55

Obesity is becoming a growing problem in developed and developing countries. Many studies report an increasing incidence of obesity in the last decade. The aim of our transversal epidemiological study was to evaluate the prevalence of overweight children, auxological characteristics and pubertal stage in healthy girls from first (200 girls), third (209), fifth (290) and seventh (223) grade of school. In this study 928 girls were evaluated through systematic school examinations in the ambulance of municipality of Karposh, Skopje. The Rome and Turkish nationality, as well as Serbian were present in a small percentage, while detailed analysis was performed in the Macedonian and Albanian population of girls. The initiation of puberty (stage M2 or P2 by Tanner) was present in Macedonian girls: 4.3% of children in first grade, 23% in third grade, and 51.7% in fifth grade. In Albanians, in first grade M2 is present in 2.7%, in third grade 5.2%, and in fifth grade 46.9%. Body mass index (BMI SDS) was +3.5 +/- 1.5 in 35% of Macedonian girls and only 5% of Albanian girls. The Macedonian girls were also significantly higher (p < 0.01) and more obese than the Albanian girls. The pubertal stage was also more advanced in Macedonian girls. Most of the obese children who were included in the study reported increased consumption of fast food. Although in the past years obesity was not a problem in our country, it is becoming more severe with every year.
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PMID:Weight, height and puberty in a cohort of Macedonian girls. 1953 61

Although randomized controlled trials demonstrated the long-term efficacy of lifestyle interventions in overweight children, the effects of these interventions in clinical practice under real-life conditions are largely unknown. One hundred twenty-nine centers specialized in outpatient pediatric obesity care participated in this quality assessment. All patients presenting before the year 2006 for lifestyle intervention of at least 6 months duration in these institutions were analyzed in a 2-year follow-up. A total of 21,784 (45% male) overweight children and adolescents aged 2-20 years (mean BMI 30.4 kg/m2, mean SDS-BMI 2.51, mean age 12.6 years) were included in the analysis. Based on an intention-to-treat analysis with variables set back to baseline in lost of follow-up, 22% of the children reduced their SDS-BMI after 6 months, 15% after 12 months, and 7% after 24 months, but only in 24, 17, and 8% of children, respectively, complete data were available. In the five treatment centers with the best outcome (518 patients), 83% of the children reduced their overweight after 6 months, 67% after 12 months, and 51% after 24 months. Under real-life conditions, most treatment centers cannot prove the long-term efficacy of their interventions due to high drop-out rate or lack of documentation. Conversely, some institutions achieved a reduction of overweight in nearly the half of their patients 24 months after baseline demonstrating the great heterogeneity in outcome. To improve the effectiveness of lifestyle interventions in real-life studying, the process and structure quality as well as their long-term results is urgently needed.
Obesity (Silver Spring) 2009 Jun
PMID:Two-year follow-up in 21,784 overweight children and adolescents with lifestyle intervention. 1958 77

Physical activity is essential in obesity management because of the impact of exercise-related energy expenditure (EE) and fat oxidation (Fox) rate on a daily balance, but the specific physiological effects of different exercise modalities are scarcely known in obese individuals. The objective of the study was to compare the metabolic responses to treadmill (TM) and cycle ergometer (CE) exercise in obese adolescents. Gas exchange, heart rate (HR), blood lactate (LA) concentration, EE and Fox were determined at different intensity levels (up to about 85% of maximal oxygen uptake) during TM and CE in 14 pubertal (Tanner stage: >3) obese (BMI SDS: 2.15-3.86) male adolescents (age: 13-18 years). At comparable HR, oxygen uptake, EE and Fox were higher, and LA lower, during TM than CE (P<0.05-0.001), suggesting that cycling imposes a metabolic involvement at the level of the single active muscles greater than walking. Therefore, due to different physiological responses to TM and CE, walking was more convenient than cycling in obese adolescents, permitting to attain the same EE at lower HR, with lower blood LA concentration and with greater Fox. These conclusions seem clinically relevant when using exercise as a part of multidisciplinary treatment for juvenile obesity and amelioration of related metabolic disturbances.
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PMID:Metabolic responses to submaximal treadmill walking and cycle ergometer pedalling in obese adolescents. 1970 3

Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. Previously, we reported that our special diet for PWS patients is effective in the long run, if started early at about 2 years of age. Our objective in this study was to investigate if our special diet is also effective in PWS adolescents who are already overweight. We provided a strict, fat-reduced, and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five adolescents (two female, three male) with PWS. Patients were prospectively followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index were recorded over that period. The special diet was started at a mean age of 16 years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m(2) (range: 32.4-55.5 kg/m(2)), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for-Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased to 33 kg/m(2) (range: 26.7-38 kg/m(2)), as well as BMI-SDS +2.7 (range: 1.7-3.4 SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special diet was still effective in reducing weight after 4-6 years, with a mean BMI of 30.5 kg/m(2) (range: 24.6-34.5 kg/m(2)) and a mean BMI-SDS of +2.1 (range: 0.7-2.9). We conclude that in a period of 2-6 years, our strict, fat-reduced, and carbohydrate-modified diet, with 10 kcal/cm height, is effective even in adolescents with PWS who are already overweight.
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PMID:A special, strict, fat-reduced, and carbohydrate-modified diet leads to marked weight reduction even in overweight adolescents with Prader-Willi syndrome (PWS). 1976 49


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