Research from JAMA — Effect of Orlistat on Weight and Body Composition in Obese Adolescents — A Randomized Controlled Trial — ContextThe prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied.ObjectiveTo determine the efficacy and safety of orlistat in weight management of adolescents.Design, Setting, and PatientsMulticenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] ≥2 units above the 95th percentile) at 32 centers in the United States and Canada.InterventionsA 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy.Main Outcome MeasuresChange in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge.ResultsThere was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (–1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group.ConclusionsIn combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.

To determine whether peptide YY (PYY), ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and satiety responses to food intake are impaired in anorexia or obesity, we studied 30 female adolescents with anorexia nervosa [body mass index (BMI) 16.3 kg/m²], obesity (BMI 34.3 kg/m²), or normal weight (BMI 20.2 kg/m²). PYY, ghrelin, GIP, insulin, and glucose concentrations and four markers of satiety were measured for 240 min after a mixed meal. The area under the curve for glucose was similar in obese (OB) and normal-weight control (C) subjects but was 15% lower in anorexic (AN) subjects. The area under the curve for insulin was 47% lower in AN and 87% higher in OB subjects, compared with C subjects. After the meal, PYY increased significantly in C (+41%, P < 0.05) but not in AN or OB adolescents. Ghrelin concentrations were highest in AN subjects and lowest in the OB group, compared with C subjects and fell significantly by 25% in all three groups. GIP concentrations were lower in AN subjects throughout the test and increased in all three groups after the mixed meal. AN adolescents reported being less hungry than OB and C adolescents. There was a negative correlation between fasting ghrelin (but not PYY or GIP) and BMI and insulin (r² = 0.33) and a positive correlation between the decrease in hunger 15 min after the meal and PYY concentrations at 15 min (r² = 0.20). In conclusion, the blunted PYY response to a meal in OB adolescents suggests that PYY plays a role in the pathophysiology of obesity. Ghrelin is unlikely to play a causal role in anorexia nervosa or obesity. The lower GIP observed in AN subjects despite a similar caloric intake may appropriately prevent an excessive insulin response in these patients.

OBJECTIVE. We designed and tested a novel health promotion program for elementary schools that was based on peer teaching from older to younger schoolchildren (“Healthy Buddies”). SUBJECTS AND METHODS. This prospective pilot study compared the effect of our program (2–3 hours/week, 21 weeks) in 2 Canadian elementary schools (intervention: n = 232 children, the whole school implementing the program; control: n = 151). Older students (4th through 7th grade) were given direct instruction from 1 intervention teacher and were paired with younger students (kindergarten through 3rd grade) for the whole school year. Students in 4th through 7th grade then acted as teachers for their younger “buddies.” All lessons included 3 components of healthy living: nutrition, physical activity, and healthy body image. The students first learned how to be positive buddies and learned the 3 components of a healthy life. Thereafter, they learned how to overcome challenges to living a healthy life. Outcome measures (intervention and control schools at the beginning and end of the school year) included validated questionnaires that assessed healthy-living knowledge, behavior and attitude, a 9-minute fitness run, self-competence, body satisfaction, disordered eating symptoms, and anthropometry (BMI, blood pressure, and heart rate). RESULTS. Compared with control students, both older and younger intervention students showed an increase in healthy-living knowledge, behavior, and attitude scores and a smaller increase in systolic blood pressure. BMI and weight increased less in the intervention students in 4th through 7th grade and height more in the intervention students in kindergarten through 3rd grade. CONCLUSIONS. Our student-led curriculum improved knowledge not only in older schoolchildren but also in their younger buddies. It also decreased weight velocity in the older students. Student-led teaching may be an efficient, easy-to-implement way of promoting a healthy lifestyle from kindergarten to 7th grade.

In rats, the respective contribution of the thyroid and peripheral tissues to the pool of T3 remains unclear. Most, if not all, of the circulating T3 produced by extrathyroidal sources is generated by 5'-deiodination of T4, catalyzed by the selenoenzyme, type I iodothyronine 5'-deiodinase (5'D-I). 5'D-I in the liver and kidney is almost completely lost in selenium deficiency, resulting in a marked decrease in T4 deiodination and an increase in circulating T4 levels. Surprisingly, circulating T3 levels are only marginally decreased by selenium deficiency. In this study, we used selenium deficiency and thyroidectomy to determine the relative contribution of thyroidal and extrathyroidal sources to the total body pool of T3. Despite maintaining normal serum T4 concentrations in thyroidectomized rats by T4 replacement, serum T3 concentrations remained 55% lower than those seen in intact rats. In intact rats, restricting selenium intake had no effect on circulating T3 concentrations. Decreasing 5'D-I activity in the liver and kidney by > 90% by restricting selenium intake resulted in a further 20% decrease in serum T3 concentrations in the thyroidectomized, T4 replaced rats, suggesting that peripheral T4 to T3 conversion in these tissues generates approximately 20% of the circulating T3 concentrations. While dietary selenium restriction markedly decreased intrahepatic selenium content (> 95%), intrathyroidal selenium content decreased by only 27%. Further, thyroid 5'D-I activity actually increased 25% in the selenium deficient rats, suggesting the continued synthesis of this selenoenzyme over selenoproteins in other tissues in selenium deficiency. These data demonstrate that the thyroid is the major source of T3 in the rat and suggest that intrathyroidal T4 to T3 conversion may account for most of the T3 released by the thyroid.