Inverse correlation of serum inflammatory markers with metabolic parameters in healthy, Black and White prepubertal youth.

OBJECTIVE: To examine for the first time the associations between pro-inflammatory cytokines and obesity-related metabolic biomarkers in, exclusively prepubertal, otherwise healthy obese and non-obese Black and White children, 7-9 years of age. DESIGN AND METHODS: Body mass index (BMI), homeostasis model assessment-estimated insulin resistance, visceral adipose tissue and subcutaneous adipose tissue (SAT (magnetic resonance imaging)); total body fat (dual-energy X-ray absorptiometry), ectopic, intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) fat (proton magnetic resonance spectroscopy) and serum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 were measured in 40 obese and non-obese children. Relationships between inflammatory cytokines and obesity were assessed by analysis of variance and Spearman's rank correlation. RESULTS: Significant inverse correlations were found between BMI z-score, SAT, total BF, and IHL and levels of TNF-α (Spearman's ρ=-0.36, -0.39, -0.43 and -0.39, respectively; P<0.05). Levels of IL-8 were significantly and inversely correlated with IMCL (-0.39; P=0.03) and remained significant after adjusting for race. IMCL was inversely associated with TNF-α only after adjusting for race (-0.37; P=0.04). CONCLUSIONS: Relationships between pro-inflammatory and metabolic markers commonly observed in adults are reversed in healthy, Black and White children before puberty. Prospective studies are warranted to determine how these inverse relationships modify chronic disease risk later in life.

Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children.

AIMS/HYPOTHESIS: We hypothesised that ectopic fat deposition is present in liver and skeletal muscle before puberty and that both are potentially important factors in the early pathogenesis of insulin resistance. METHODS: Proton magnetic resonance spectroscopy was used to evaluate intramyocellular and intrahepatic lipids in 50 male and 42 female multi-ethnic, prepubertal (Tanner < 2) children (8.1 ± 0.8 years; 35.4 ± 10.7 kg; 27.9 ± 8.3% body fat; means ± SD). Intramyocellular lipid was measured in soleus muscle and intrahepatic lipid in the middle right lobe. Abdominal fat was measured by magnetic resonance imaging, body fat by dual energy X-ray absorptiometry, and insulin resistance using homeostatic model assessment. RESULTS: Intrahepatic lipid ranged from 0.11% to 4.6% relative to the liver water signal (mean 0.79 ± 0.79%) whereas intramyocellular lipid ranged from 0.13% to 1.86% relative to the muscle water signal (mean 0.51 ± 0.28%). Intramyocellular and intrahepatic lipids were significantly correlated with total adiposity (r = 0.49 and 0.59), abdominal adiposity (r = 0.44 and 0.54), and each other (r = 0.39, p < 0.05, Spearman). Both intramyocellular and intrahepatic lipid were positively correlated with fasting insulin (r = 0.37 and 0.38 respectively) and insulin resistance (r = 0.37 and 0.37; p < 0.01). After adjustment for race and sex, the relations between ectopic fat and insulin resistance remained, whereas both disappeared when further adjusted for body fat or BMI z scores. CONCLUSIONS/INTERPRETATIONS: These results suggest that typical relations between body composition, ectopic fat and insulin resistance are present in children before puberty. Thus, interventions aimed at reducing adiposity have the potential to decrease ectopic fat accumulation, delay the onset of insulin resistance and decrease the risk for development of type 2 diabetes in children.

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.

Racial differences in intracerebral haemorrhage outcomes in patients with obesity.

OBJECTIVE: This study was conducted to determine the role of obesity and race in intracerebral haemorrhage (ICH) outcomes. METHODS: The Get with the guideline-Stroke database was queried for all admitted patients with spontaneous ICH. Secondary causes of ICH were excluded. Body mass index (BMI) was classified using the Center for Disease Control guidelines. Race was classified as White or non-White. Demographics, clinical, imaging data were retrieved. Outcome measures were hematoma expansion at 24 h and discharge disposition. RESULTS: A total of 428 patients were included in our analysis. Female gender, past history of congestive heart failure, diabetes mellitus, HbA1c, blood pressure, ICH volume, ICH location, intraventricular haemorrhage and hospital length of stay deferred across BMI categories. On multivariate analysis, along with obese categories, age, ICH location and ICH volume were independent predictors of poor outcomes (hematoma expansion and poor discharge disposition). After adjusting for these variables, obesity remained a predictor of poor disposition outcome compared with normal and overweight subjects; Normal vs. Obese OR 0.26 CI 0.115-0.593 p = 0.0014; Obese vs. Overweight OR 3.79 CI 1.68-8.52 p = 0.0013. Nonetheless, obesity did not influence hematoma expansion. Overall, BMI-race classification did not influence outcomes. However, among non-Whites, the obese category had higher odds of a poor disposition outcome than normal (OR 6.84 CI 2.12-22.22 p = 0.0013) or overweight (OR 8.45 CI 2.6-27.49 p = 0.0004) categories. CONCLUSION: An obesity paradox in ICH was not observed in our cohort. In the non-White population, patients with obesity were likely to be associated with poor disposition outcome. Similar findings were not observed in White population.

Association of depression with Body Mass Index, sedentary behavior, and maladaptive eating attitudes and behaviors in 11 to 13-year old children.

We examined the relation of different behavioral dimensions of depression with weight-related variables (BMI percentile, sedentary behavior, eating attitudes, and weight control behaviors) in children aged 11 to 13 years. Depression was assessed using the Children's Depression Inventory (CDI). Sedentary behavior was measured in 45 sixth grade students (23 boys and 22 girls) using a validated 24-hour recall instrument, the Self-Administered Physical Activity Checklist. BMI was calculated directly from measured height and weight (kg/m2). The Children's Eating Attitudes Test (ChEAT) was used to measure eating attitudes and weight control behaviors. There were not significant gender differences in reported minutes (142 vs. 91 minutes for boys vs. girls; p=0.25) of sedentary behavior (i.e., television watching and video game playing). The major finding of this study was that certain aspects of depression (i.e., interpersonal problems and feelings of ineffectiveness) were correlated with higher levels of sedentary behavior in children aged 11 to 13. A factor analysis of the study variables indicated that most dimensions of depression, sedentary behavior, and body size represent distinct but correlated behavioral dimensions. This study provides support for a link between specific aspects of depression (i.e., interpersonal problems and feelings of ineffectiveness) and sedentary behavior in children.

Pre-school obesity is inversely associated with vegetable intake, grocery stores and outdoor play.

The study determined the association between body mass index (BMI) z score and fruit and vegetable intake, frequency and ratio of fast food outlets and grocery stores in concentric areas around the child's residence, outdoor play and total crime index. Data from 78 Louisiana pre-school children were analyzed using Pearson's correlation and multiple regression analysis. Parental-reported fruit intake was linearly associated with increased number of grocery store counts in concentric areas around the child's residence (P = 0.0406, P = 0.0281). Vegetable intake was inversely (P = 0.04) and the ratio of fast food outlets to grocery stores in a 2-mile concentric area around the child's residence was positively (P = 0.05) associated to BMI z score after applying Best Model regression analysis (F = 3.06, P = 0.0346). Children residing in neighbourhoods with greater access to fast foods and lower access to fruits and vegetables may be at higher risk for developing obesity during pre-school years.

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.

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.

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.

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.

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.

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.

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.

Comparison of the validity of anthropometric and bioelectric impedance equations to assess body composition in adolescent girls.

OBJECTIVE: The purpose of this study was to examine the validity of two anthropometric and four bioelectric impedance (BIA) equations to estimate body composition from dual-energy x-ray absorptiometry (DXA) in adolescent girls of various ethnicities. The rationale for this study was to develop a prediction equation for percent body fat in a multi-ethnic, representative sample of sixth to eighth grade girls. DESIGN: One-hundred and sixty-six girls (51 African-American, 45 non-Black Hispanic, 55 non-Hispanic Caucasian, 15 multi-ethnic) participated. Estimates of percent fat and fat-free mass (FFM) from six published BIA and anthropometric equations and the equation developed from this study were compared to body composition determined from DXA. An RJL Systems analyzer was used to measure BIA. Anthropometry included body weight, height, and triceps and calf skinfolds. RESULTS: Average (± SD) age, size and body composition was as follows: age, 12.1±1.2 yrs, body mass 52.7±15.9 kg, height, 154.6±8.1 cm; DXA percent fat, 27.9±10.4; fat mass (FM), 15.6±10.2 kg; and fat free mass (FFM) 35.7±6.8 kg. No ethnic differences were found in the relationships between estimated and DXA measured body composition, with the exception of the skinfold equation. The six equations explained on average 82% of the variance in percent fat, 94% of the variance in fat mass, and 88% in fat free mass. Bland-Altman analysis indicated that none of the equations performed satisfactorily in our sample. CONCLUSIONS: The BIA and anthropometric equations were significantly related to DXA body composition parameters, however none met the criteria for cross-validation.

Scaling VO(2) peak in obese and non-obese girls.

OBJECTIVE: The conventional ratio method (milliliters O(2) per mass) typically is used to express VO(2) peak. The goal of the current study was to compare VO(2) peak of obese girls with normal-weight girls by ratio and allometric scaling methods. RESEARCH METHODS AND PROCEDURES: We compared VO(2) peak by ratio and allometric methods in 46 obese and 47 normal-weight girls. Indirect calorimetry was used to measure VO(2) peak during either treadmill running or walking. Regression analysis was used to determine coefficients for mass and stature for each group with ANOVA used to compare data between groups. RESULTS: The obese girls were taller and had higher values of body fatness (p < or = 0.05). Absolute VO(2) peak (liters per minute) was similar between groups; however VO(2) peak relative to mass was 50% lower (p < or = 0.05) in the obese girls. When VO(2) peak (milliliters per minute per kilogram) and mass were correlated, r = -0.48 was found in the obese group. Allometric scaling of logarithmic transformed stature and mass reduced this to r = -0.002, thus eliminating the bias associated with the ratio method. Adjusting VO(2) peak allometrically scaled for mass, stature, and the combination of mass and stature reduced the difference between groups from 50% (ratio method) to 10% to 11% (p < or = 0.05) with higher values found in the normal-weight girls. DISCUSSION: These results demonstrate the bias associated with the ratio method when comparing VO(2) peak in obese girls with VO(2) peak in normal-weight girls. Allometric scaling eliminated the bias and thus may reflect a truer comparative response.