Claude Marcus

Interventions to prevent obesity in children and adolescents: a systematic literature review

Objective:Preventive measures to contain the epidemic of obesity have become a major focus of attention. This report reviews the scientific evidence for medical interventions aimed at preventing obesity during childhood and adolescence.Design:A systematic literature review involving selection of primary research and other systematic reviews. Articles published until 2004 were added to an earlier (2002) review by the Swedish Council on Technology Assessment in Health Care.Methods:Inclusion criteria required controlled studies with follow-up of at least 12 months and results measured as body mass index, skinfold thickness or the percentage of overweight/obesity. Children could be recruited from normal or high-risk populations.Results:Combining the new data with the previous review resulted in an evaluation of 24 studies involving 25 896 children. Of these, eight reported that prevention had a statistically significant positive effect on obesity, 16 reported neutral results and none reported a negative result (sign test; P=0.0078). Adding the studies included in five other systematic reviews yielded, in total, 15 studies with positive, 24 with neutral and none with negative results. Thus, 41% of the studies, including 40% of the 33 852 children studied, showed a positive effect from prevention. These results are unlikely to be a random chance phenomenon (P=0.000061).Conclusion:Evidence shows that it is possible to prevent obesity in children and adolescents through limited, school-based programs that combine the promotion of healthy dietary habits and physical activity.

Response of Severely Obese Children and Adolescents to Behavioral Treatment

OBJECTIVES To investigate whether the degree of obesity predicts the efficacy of long-term behavioral treatment and to explore any interaction with age. DESIGN A 3-year longitudinal observational study. Obese children were divided into 3 age groups (6-9, 10-13, and 14-16 years) and also into 2 groups (moderately obese, with a body mass index [BMI]-standard deviation [SD] score [or z score] of 1.6 to <3.5, and severely obese, with a BMI-SD score of ≥3.5). SETTING National Childhood Obesity Center, Stockholm, Sweden. PARTICIPANTS Children 6 to 16 years of age who started treatment between 1998 and 2006. INTERVENTION Behavioral treatment of obesity. MAIN OUTCOME MEASURE Change in BMI-SD score during 3 years of treatment; a reduction in BMI-SD score of 0.5 units or more was defined as clinically significant. RESULTS A total of 643 children (49% female children) met the inclusion criteria. Among the youngest moderately obese children, 44% had a clinically significant reduction in BMI-SD score (mean reduction, -0.4 [95% CI, -0.55 to -0.32]). Treatment was less effective for the older moderately obese children. Twenty percent of children who were 10 to 13 years of age and 8% of children who were 14 to 16 years of age had a reduction in BMI-SD score of 0.5 units or more; 58% of the severely obese young children showed a clinically significant reduction in BMI-SD score (mean reduction, -0.7 [95% CI, -0.80 to -0.54]). The severely obese adolescents showed no change in mean BMI-SD score after 3 years, and 2% experienced clinically significant weight loss. Age was found to be a predictor of a reduction in BMI-SD score (odds ratio, 0.68 units per year [95% CI, 0.60-0.77 units per year]). CONCLUSIONS Behavioral treatment was successful for severely obese children but had almost no effect on severely obese adolescents.

Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers.

BACKGROUND Japanese longevity is the highest in the world. This is partly explained by low occurrence of cardiovascular diseases, which in turn is attributed to the Japanese traditional diet (JTD). Recent research demonstrates that nitric oxide (NO), a key regulator of vascular integrity, can be generated from nitrate (NO(3)(-)), abundantly found in vegetables. It can reduce blood pressure (BP) via its serial reduction to nitrite (NO(2)(-)) and to bioactive NO. Interestingly, JTD is extremely rich in nitrate and the daily consumption is higher than in any other known diet. OBJECTIVE AND DESIGN In a randomized, cross-over trial we examined the effect of a 10-day period of JTD on blood pressure in 25 healthy volunteers. Traditional Japanese vegetables were encouraged to be consumed and avoided during the control period. Daily nitrate intake was calculated. RESULTS Nitrate naturally provided by the JTD was 18.8 mg/kg/bw/day, exceeding the Acceptable Daily Intake by five times (ADI, 3.7 mg/kg/bw). Plasma and salivary levels of nitrate and nitrite were higher at the end of the JTD period. Diastolic BP decreased on average 4.5 mmHg during JTD compared to the control diet (P=0.0066) while systolic BP was not affected. This effect was evident in normotensive subjects and similar to that seen in the recent studies. CONCLUSIONS An ordinary nitrate rich diet may positively affect blood pressure. Our findings further support the importance of the role of dietary nitrate on BP regulation suggesting one possible explanation of healthy aspects of traditional Japanese food.

Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone Deficiency

CONTEXT The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. DESIGN AND SETTING A randomized, controlled, long-term multicenter trial was conducted in Sweden. INTERVENTION Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated. SUBJECTS A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. MAIN OUTCOME MEASURES We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS. RESULTS After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.

Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes

Recent studies have shown that SNPs in the FTO gene predispose to childhood and adult obesity. In this study, we examined the association between variants in FTO and KIAA1005, a gene that maps closely to FTO, and obesity, as well as obesity related traits among 450 well characterised severely obese children and 512 normal weight controls. FTO showed significant association with several obesity related traits while SNPs in KIAA1005 did not. When stratified by gender, the FTO variant rs9939609 showed association with obesity and BMI among girls (P=0.006 and 0.004, respectively) but not among boys. Gender differences were also found in the associations of the FTO rs9939609 with obesity related traits such as insulin sensitivity and plasma glucose. This study suggests that FTO may have an important role for gender specific development of severe obesity and insulin resistance in children.

A 4-year, cluster-randomized, controlled childhood obesity prevention study: STOPP.

Objective:To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children.Design:Cluster-randomized, controlled study.Subjects:A total of 3135 boys and girls in grades 1–4 were included in the study.Methods:Ten schools were selected in Stockholm county area and randomized to intervention (n=5) and control (n=5) schools. Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools. Physical activity (PA) was aimed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time. PA was measured by accelerometry. Eating habits at home were assessed by parental report. Eating disorders were evaluated by self-report.Results:The prevalence of overweight and obesity decreased by 3.2% (from 20.3 to 17.1) in intervention schools compared with an increase of 2.8% (from 16.1 to 18.9) in control schools (P<0.05). The results showed no difference between intervention and controls, after cluster adjustment, in the longitudinal analysis of BMIsds changes. However, a larger proportion of the children who were initially overweight reached normal weight in the intervention group (14%) compared with the control group (7.5%), P=0.017. PA did not differ between intervention and control schools after cluster adjustment. Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention. There was no difference between children in intervention and control schools in self-reported eating disorders.Conclusions:A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home. The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA.

Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity.

Accessory to Obesity? Melanocortin receptors are a family of cell membrane receptors that control diverse physiological functions. Mutations in the gene encoding melanocortin 4 receptor (MC4R) are a cause of familial early-onset obesity. Asai et al. (p. 275) studied the function of an accessory protein for MC4R signaling, MRAP2, and found that mice genetically deficient in MRAP2 develop severe obesity. Sequencing of MRAP2 in unrelated, severely obese humans revealed one individual with a clearly disruptive genetic variant, suggesting that MRAP2 mutations might also be a rare cause of human obesity. In a zebrafish model, Sebag et al. (p. 278) studied two paralogs of the MRAP2 accessory protein, one of which enhanced MC4R responsiveness to α–melanocyte-stimulating hormone, which regulates feeding and growth. Disruption of a protein required for effective signaling by a melanocortin receptor causes severe obesity in mice. Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro. To investigate the physiological role of brain-expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized mice with whole-body and brain-specific targeted deletion of Mrap2, both of which develop severe obesity at a young age. Mrap2 interacts directly with melanocortin 4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it enhances Mc4r-mediated generation of the second messenger cyclic adenosine monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism underlying the association between Mrap2 disruption and obesity. In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans.

Two-year outcome of laparoscopic Roux-en-Y gastric bypass in adolescents with severe obesity: results from a Swedish Nationwide Study (AMOS)

CONTEXT:The prevalence of obesity among adolescents has increased and we lack effective treatments.OBJECTIVE:To determine if gastric bypass is safe and effective for an unselected cohort of adolescents with morbid obesity in specialized health care.DESIGN, SETTING AND PATIENTS:Intervention study for 81 adolescents (13–18 years) with a body mass index (BMI) range 36–69 kg m−2 undergoing laparoscopic gastric bypass surgery in a university hospital setting in Sweden between April 2006 and May 2009. For weight change comparisons, we identified an adult group undergoing gastric bypass surgery (n=81) and an adolescent group (n=81) receiving conventional care.MAIN OUTCOME MEASUREMENTS:Two-year outcome regarding BMI in all groups, and metabolic risk factors and quality of life in the adolescent surgery group.RESULTS:Two-year follow-up rate was 100% in both surgery groups and 73% in the adolescent comparison group. In adolescents undergoing surgery, BMI was 45.5±6.1 (mean ±s.d.) at baseline and 30.2 (confidence interval 29.1–31.3) after 2 years (P<0.001) corresponding to a 32% weight loss and a 76% loss of excess BMI. The 2-year weight loss was 31% in adult surgery patients, whereas 3% weight gain was seen in conventionally treated adolescents. At baseline, hyperinsulinemia (>20 mU l−1) was present in 70% of the adolescent surgery patients, which was reduced to 0% at 1 year and 3% at 2 years. Other cardiovascular risk factors were also improved. Two-thirds of adolescents undergoing surgery had a history of psychopathology. Nevertheless, the treatment was generally well tolerated and, overall, quality of life increased significantly. Adverse events were seen in 33% of patients.CONCLUSIONS:Adolescents with severe obesity demonstrated similar weight loss as adults following gastric bypass surgery yet demonstrating high prevalence of psychopathology at baseline. There were associated benefits for health and quality of life. Surgical and psychological challenges during follow-up require careful attention.

Orlistat treatment in obese prepubertal children: a pilot study

Aim: This study investigated orlistat treatment in obese prepubertal children with regard to tolerance, safety and psychological well‐being. Methods: 11 healthy, severely obese prepubertal children (age 8.3–12.3 y, body mass index standard deviation score 5.3–9.2) were recruited for a 12wk open treatment. Before, during and after treatment, the participants were investigated by psychological evaluation, blood chemistry, and parameters reflecting obesity and fat mass. Results: The participants were able to comply with the treatment, as indicated by pill counts and self reports, and expressed a desire to continue the treatment after the study period. Gastrointestinal side effects were mild and tolerable. No negative effects on psychological or physical well‐being were detected, and the psychological evaluation demonstrated increased avoidance of fattening food, body shape preoccupation and oral control (p= 0.011). The median weight loss was 4.0 kg (range –12.7 to +2.5 kg, p= 0.016) and was highly correlated to decreased fat mass (regression coefficient 0.953, p < 0.01).

Physical activity patterns measured by accelerometry in 6- to 10-yr-old children.

PURPOSE To examine differences in patterns of objectively measured physical activity (PA) among weekdays and weekend days and across different time blocks during the day in relation to age and gender. This knowledge is important when planning preventive initiatives aimed at increasing levels of PA in children. METHODS This is a cross-sectional analysis in 653 girls and 640 boys (6-10 yr) measured during 1 wk with accelerometry. Periods of the day were divided into school time (8:00 a.m. to 1:30 p.m.), after school care time (1:30-4:00 p.m.), and evening time (4:00-9:00 p.m.). Multivariate ANOVA was used to analyze mean PA. RESULTS Mean daily PA differed significantly across age groups (6-10 yr) in both boys and girls (P < 0.001). Mean (SE) daily PA was significantly lower during weekends compared with weekdays in all age groups (girls 782 (6.7) vs 681 (7.7) counts per min (CPM), P < 0.001; boys 853 (7.1) vs 729 (8.0) CPM, P < 0.001). This decline was similar across low, medium, and highly active children. Mean PA was highest during after school care time on weekdays (girls 879 (9.8) and boys 990 (10.0) CPM) compared with all other periods. The difference in mean PA between boys and girls was highest during school time (P < 0.001) and after school care time (P < 0.001). CONCLUSIONS The decline in PA in children may start already at the age of 6 yr. The school setting may be an important arena for targeting activity levels in girls because the difference in PA levels between girls and boys is most pronounced during school time. In both girls and boys, PA levels are disproportionally low during weekends and might be important targets for interventions aimed to increase PA.