Template to improve glycemic control without reducing adiposity or dietary fat.

Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches.

Exercise as a modality in the treatment of childhood obesity.

In a review of the literature, Glenny et al determined that family therapy and lifestyle modification seem to be effective in the prevention and treatment of childhood but not necessarily adult obesity. Furthermore, research indicates that obese children are better able to maintain weight loss over a long-term period than are adults. Based on the limited research in the treatment of obesity in children, approaches should include family interventions with nutrition and physical activity education, structured exercise, and behavior modification. These interventions should be delivered by a team of health care experts in a nurturing, nonintimidating environment; however, obese children respond differently physiologically and emotionally to exercise than do normal-weight children. Therefore, obese children may experience negative consequences to participation in activities considered appropriate for normal-weight children. In clinical settings, specialized exercise programs based on appropriate theories that include specific recommendations for children with varied obese conditions have been shown to enhance safety, efficacy, and compliance during pediatric obesity treatment. Optimal results may be achieved by combining programs to reduce sedentary behaviors based on similar theories with specialized, structured exercise prescriptions. When used in conjunction with appropriate dietary prescriptions and consistent behavior modification, exercise serves as a promising modality that may reverse obese conditions during childhood and, perhaps, prevent the onset of adult obesity.

Impact of significant weight loss on maximal oxygen uptake in obese children and adolescents.

BACKGROUND: The prevalence of pediatric obesity has increased over the past few decades in all ethnic, gender, and age groups. The treatment of obesity, especially in children with moderate to severe conditions, is difficult. In this study, we examined the impact of significant weight loss as a result of participation in a multi-disciplinary weight management program on maximal oxygen uptake (VO2max) in obese children and adolescents. METHODS: Eleven obese children and adolescents (7 to 14 years of age; mean age, 12.3 +/- 1.9 years) were enrolled in a weight management program at the Children's Hospital of New Orleans. The treatment program included a high-protein, very low-calorie diet (VLCD; protein intake, 1.5 to 2.0 g/kg of ideal body weight per day; and 800 kcal/d). Diets were supplemented with extra fluid, minerals, and vitamins. All subjects attended weekly 2-hour clinic sessions. During these sessions, they received nutrition instruction, participated in a moderate-intensity, progressive exercise program, and learned behavior-modification techniques. Weight, height, body mass index ([BMI]; wt/ht2), and VO2max by indirect calorimetry were obtained at enrollment and at the end of 10 weeks of treatment. RESULTS: There was a significant decrease in body weight after 10 weeks. The BMI decreased significantly from 34.1 +/- 4.8 on entry to 29.4 +/- 3.5 (mean +/- SD; P < 0.0001). Despite the significant weight loss, VO2max increased significantly (P < 0.001) from entry (19.2 +/- 3.0 mL/kg/min) to completion of 10 weeks (22.4 +/- 5.8 mL/kg/min). However, absolute VO2max L/min was unchanged. CONCLUSIONS: We conclude that relative VO2max mL/kg/min is significantly improved in obese youth after significant weight loss with a VLCD and moderate-intensity, progressive exercise. However, because absolute VO2max L/min was unchanged, this improvement seems to result from the reduction in total body weight as opposed to the effect of the moderate-intensity exercise intervention.

Safety, feasibility, and efficacy of a resistance training program in preadolescent obese children.

BACKGROUND: Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. Resistance or strength training has been prescribed for adult obese persons. Research is limited concerning the use of resistance training in programs that treat obese preadolescents. METHODS: Nineteen treatment subjects (7-12 years of age) were enrolled in a 10-week weight management program which included diet, behavior modification, and aerobic and flexibility exercises. Forty-eight control subjects (7-12 years of age) participated in the diet, behavior modification program, and a thrice-a-week walking program. The efficacy of the overall weight management program was examined by anthropometry at 10 weeks and 1 year. RESULTS: Fifteen treatment subjects completed the 10-week program (retention rate, 78.9%). Thereafter compliance decreased by approximately 33% for the long-term study. Seventeen control subjects completed the program (retention rate, 35%). Weight, percent of ideal body weight, and body mass index were reduced significantly at 10 weeks (P<0.0001) and did not increase significantly at 1-year follow-up in both treatment and control groups. Height increased significantly at 1 year in both treatment and control subjects. In the treatment subjects, percent fat decreased significantly (P<0.001), whereas fat-free mass did not change significantly (P>0.05). CONCLUSIONS: A resistance-training program may be included safely in a multidisciplinary weight management program for obese preadolescent male and female children. The addition of specific exercise regimes such as resistance training may improve program retention especially in severely obese youth.

Lipid profiles of obese children and adolescents before and after significant weight loss: differences according to sex.

BACKGROUND: Childhood obesity has been associated with elevated serum levels of total cholesterol, triglycerides, and low-density lipoproteins (LDLs). We observed the lipid profiles of obese female subjects versus obese male subjects before and after significant weight loss. METHODS: We studied 29 girls and 21 boys enrolled in a multidisciplinary weight reduction program. RESULTS: Measures were taken at enrollment and at 10 weeks. Significant improvements were observed for changes in percentage of ideal body weight and total cholesterol and triglyceride levels. In addition, LDL decreased significantly in girls but not in boys. CONCLUSIONS: A combination of diet, behavior modification, and exercise, is an effective instrument for lowering total cholesterol and triglyceride levels in obese children. In addition, girls tend to be more susceptible to a decrease in LDL level, which might result in an increased cardiovascular protective effect.

Recent advances in the treatment of childhood obesity.

The rapid increase in the prevalence of obesity in the last decade indicates a need for effective treatment programs. We conducted a short-term, repeated-measures, clinical-outcome trial in three groups of children and adolescents in two different locations. Two cohorts (n=34) were enrolled in a 36-wk multi-disciplinary weight-management program at the Children's Hospital of New Orleans. One cohort (n=16) was enrolled in a similar intervention at the General Clinical Research Center (GCRC) at the Medical Center of Louisiana for a 10-wk summer weight-loss program. Subjects were offered a protein-sparing modified fast (PSMF) diet (600-800 kcal/d; 2 g protein/kg body weight), followed by a balanced hypocaloric diet, and they participated in behavior-modification sessions and a moderate-intensity (45-55% volume of oxygen consumed at maximal effort [VO(2)max]), progressive exercise program. The following parameters were examined at baseline, 10 wk, and 36 wk (cohort 1 only): Weight, height, percentage of ideal body weight (%IBW), relative body fat (%fat), fat free body (FFB) mass, estimated VO(2)max mL/kg min(BW) [adjusted for body weight]), blood chemistries, lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein [LDL], high-density lipoprotein [HDL], and insulin-like growth factor-1 [IGF-1]). All three groups experienced significant decreases in weight, %IBW and %fat at 10 wk. The weight loss was maintained at 26 wk in cohorts 1 and 2, and at 36 wk in cohort 1. There were no significant decreases in height velocity during the study. In addition, measures of estimated VO(2)max mL/kg/min(BW) and IGF-1 parameters were significantly greater at 10 wk compared to baseline. Measures of TC, TG, and LDL were significantly lower at 10 wk, with no significant changes noted in HDL. We conclude that a multi-disciplinary weight-management program, including PSMF, behavior modification, and exercise, provides an effective method of treatment for obesity in children and adolescents. Long-term, randomized, and controlled clinical trials are needed to confirm the results of this preliminary, short-term observation.

A multidisciplinary approach to the treatment of childhood obesity.

Childhood obesity is a chronic disease that is associated with significant co-morbidity. Successful treatment and prevention of childhood obesity requires a multidisciplinary approach, including diet, nutrition education, behavior modification, and exercise. We studied 87 children (39 males, 48 females; aged 7-17 years) enrolled in a one-year multidisciplinary weight reduction program. Subjects were placed on a very low calorie/high protein diet, a moderate-intensity progressive exercise program, and behavior modification sessions for 10 weeks. Measures were taken at baseline 10 weeks, and 1 year. Significant anthropometric changes in weight, percent of ideal body weight, and percent body-fat were observed in all patients. We conclude that a multidisciplinary weight reduction program including diet, behavior modification, and exercise is an effective instrument to achieve weight loss in obese children and adolescents.

Inclusion of resistance exercise in a multidisciplinary outpatient treatment program for preadolescent obese children.

BACKGROUND: Safe and effective exercise programs are needed to prevent and treat chronic diseases in childhood. In particular, preadolescent obese children should participate in activities that are specific to their special needs. METHODS: We included a moderate intensity, progressive resistance training program in a multidisciplinary weight management program for obese preadolescent children. The program included diet, behavior modification, and aerobic and flexibility exercises. RESULTS: The subjects reported no accidents or injuries and 100% compliance with the minimum required exercise prescription. Weight, percent ideal body weight, body mass index, and percent fat were reduced significantly at 10 weeks and did not increase significantly at 1 year follow-up. Height and lean body mass increased significantly at 1 year. CONCLUSION: A resistance training program may be safely included in a multidisciplinary weight management program for obese preadolescent children.

Motivating the obese child to move: the role of structured exercise in pediatric weight management.

BACKGROUND: The prevalence of childhood obesity is rapidly increasing. Successful prevention and treatment of childhood obesity depends on increasing the physical activity patterns of obese youth. However, motivating the obese child to participate in physical activity is difficult. METHODS: We designed a four-phase physical activity intervention, consisting of a structured progressive exercise program of moderate intensity, along with motivational methods to increase physical activity and improve body movement awareness. RESULTS: Seventy-three overweight children participated in the weight management program. They had a significant weight loss and reduction in body fat, which was maintained at 1-year follow-up. Subjects also maintained lean body mass and showed improved physical activity patterns. CONCLUSIONS: Progressive exercise, used in conjunction with nutrition and behavior modification, provides successful motivational strategies. These strategies encourage increased physical activity patterns, the adoption of regular structured exercise training, and the loss of excess body fat.

The impact of significant weight loss on resting energy expenditure in obese youth.

BACKGROUND: The prevalence of obesity in American youth is increasing and treating the condition is difficult. METHODS: We have developed a multidisciplinary weight-reduction program that includes a very low calorie diet followed by a hypocaloric diet, exercise, and behavior modification. Based on data collected at baseline and at the end of the acute intervention phase (10 weeks), we assessed the impact of the weight loss that resulted from participation in this weight reduction program on the resting energy expenditure and body composition of obese children and adolescents. RESULTS: There was a significant decrease in body weight and body fat as assessed by weight determinations and skin-fold measurements after 10 weeks. The body mass index decreased significantly from 33.8 on entry to 29.6 (P < 0.0001). Despite the significant weight loss, resting energy expenditure and lean body mass remained constant from entry until the completion of the acute phase. CONCLUSION: We conclude that a multidisciplinary weight-reduction program that combines a very low calorie diet followed by a balanced hypocaloric diet, with a moderate-intensity progressive exercise program and behavior modification is an effective means for weight-reduction in obese children and adolescents. Furthermore, fat mass is significantly reduced while lean body mass and resting energy expenditure are unaltered.

Hepatic insulin clearance increases after weight loss in obese children and adolescents.

BACKGROUND: Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population. METHODS: We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention. RESULTS: All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss. CONCLUSIONS: Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.

The health benefits of physical activity in children and adolescents: implications for chronic disease prevention.

UNLABELLED: Clinical, epidemiological and basic research evidence clearly supports the inclusion of regular physical activity as a tool for the prevention of chronic disease and the enhancement of overall health. In children, activities of a moderate intensity may enhance overall health, and assist in preventing chronic disease in at-risk youth. The numerous health benefits of regular exercise are dependent on the type, intensity and volume of activity pursued by the individual. These benefits include reduction of low density lipoproteins while increasing high density lipoprotein; improvement of glucose metabolism in patients with type II diabetes; improved strength, self esteem and body image; and reduction in the occurrence of back injuries. In addition, a progressive, moderate-intensity exercise program will not adversely effect the immune system and may have a beneficial effect on the interleukin-2/natural killer cell system. Furthermore, by decreasing sedentary behaviors and, thus, increasing daily physical activity, individuals may experience many stress-reducing benefits, which may enhance the immune system. CONCLUSION: Moderate intensity exercise of a non-structured nature seems to facilitate most of the disease prevention goals and health promoting benefits. With new guidelines promoting a less intense and more time-efficient approach to regular physical activity, it is hoped that an upward trend in the physical activity patterns, and specifically children at risk for chronic disease, will develop in the near future.

Recent advances in the treatment of childhood obesity.

The multidisciplinary, four-phase approach, which includes PSMF, BEM, and MPE is successful in treating mild, moderate, and severe degrees of childhood and adolescent obesity. The MPE program is appropriate for use with PSMF and BEM due to its progressive nature, variety of options, and moderate intensity level. In addition, the MPE program is of sufficient intensity, duration, and frequency to promote a significant increase in estimated aerobic capacity (VO2max) and to promote the maintenance of lean body mass and resting energy expenditure. The short-term intervention of PSMF, BEM, and MPE also results in an improvement in body composition, lipid profiles, and IGF-1 and T3 levels. The 1200-calorie balanced diet, MPE, and BEM also provide a successful method of weight maintenance in children and adolescents, as indicated by further improvement in body composition at the 26-week measure. Additional studies are needed to assess the contribution of exercise to the maintenance of lean body mass and resting energy expenditure in obese children and adolescents. In addition, it will be important to assess long-term weight maintenance in obese adolescents who effectively lose weight in this multidisciplinary program.