Naltrexone/Bupropion extended release-induced weight loss is independent of nausea in subjects without diabetes.

Naltrexone/bupropion extended release (NB) is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of ≥30 or ≥27 kg m(-2) and ≥1 weight-related comorbidity (e.g. hypertension, type 2 diabetes and dyslipidaemia). In phase 3 clinical studies, nausea occurred in significantly higher proportions of subjects randomized to NB vs. placebo (PBO). In this pooled analysis of three phase 3, 56-week, PBO-controlled studies, we characterized nausea and weight loss in NB- and PBO-treated subjects without diabetes. Subjects receiving NB (n = 1778) lost significantly more weight than those receiving PBO (n = 1160). Weight change was not significantly different between subjects reporting and not reporting nausea in either treatment arm. Severity of nausea was mild to moderate in ≥95% of all cases. In the NB arm, the highest incidence of nausea onset (9%) was reported during week 1. The median duration of mild, moderate and severe nausea in subjects receiving NB was 14, 9 and 13 days, respectively. Our results demonstrate that nausea associated with NB is rarely severe, primarily occurs early in treatment and is not a contributor to weight loss.

Impact of parental weight status on a school-based weight management programme designed for Mexican-American children.

BACKGROUND: While overweight and obese children are more likely to have overweight or obese parents, less is known about the effect of parental weight status on children's success in weight management programmes. OBJECTIVES: This study was a secondary data analysis of a randomized controlled trial and investigated the impact of having zero, one or two obese parents on children's success in a school-based weight management programme. METHODS: Sixty-one Mexican-American children participated in a 24-week school-based weight management intervention which took place in 2005-2006. Children's heights and weights were measured at baseline, 3, 6 and 12 months. Parental weight status was assessed at baseline. Repeated measures anova and ancova were conducted to compare changes in children's weight within and between groups, respectively. RESULTS: Within-group comparisons revealed that the intervention led to significant decreases in standardized body mass index (zBMI) for children with zero (F = 23.16, P < .001) or one obese (F = 4.99, P < .05) parent. Between-group comparisons indicated that children with zero and one obese parents demonstrated greater decreases in zBMI compared to children with two obese parents at every time point. CONCLUSIONS: The school-based weight management programme appears to be most efficacious for children with one or no obese parents compared to children with two obese parents. These results demonstrate the need to consider parental weight status when engaging in childhood weight management efforts.

Excess body mass is associated with T cell differentiation indicative of immune ageing in children.

Obesity has been associated with accelerated biological ageing and immunosenescence. As the prevalence of childhood obesity is increasing, we wanted to determine if associations between obesity and immunosenescence would manifest in children. We studied 123 Mexican American adolescents aged 10-14 (mean 12·3 ± 0·7) years, with body weights ranging from 30·1 to 115·2 kg (mean 52·5 ± 14·5 kg). Blood samples were obtained to determine proportions of naive, central memory (CM), effector memory (EM), senescent and early, intermediate and highly differentiated subsets of CD4(+) and CD8(+) T cells. Overweight and obese children had significantly lowered proportions of early CD8(+) T cells (B = -11·55 and -5·51%, respectively) compared to healthy weight. Overweight children also had more EM (B = +7·53%), late (B = +8·90%) and senescent (B = +4·86%) CD8(+) T cells than healthy weight children, while obese children had more intermediate CD8(+) (B = +4·59%), EM CD8(+) (B = +5·49%), late CD4(+) (B = +2·01%) and senescent CD4(+) (B = +0·98%) T cells compared to healthy weight children. These findings withstood adjustment for potentially confounding variables, including age, gender and latent cytomegalovirus and Epstein-Barr virus infections. We conclude that excess body mass, even in adolescence, may accelerate immunosenescence and predispose children to increased risks of incurring immune-related health problems in adulthood.

Effectiveness of Medifast supplements combined with obesity pharmacotherapy: a clinical program evaluation.

PURPOSE: To evaluate the long-term impact of Medifast meal-replacement supplements (MMRS) combined with appetite suppressant medication (ASM) among participants who received 52 weeks of treatment. METHODS: We conducted a systematic program evaluation of weight loss data from a medically-supervised weight control program combining the use of MMRS and ASM. Data were obtained and analyzed from 1,351 patient (BMI> or =25) medical charts who had participated for at least 12 weeks of treatment. Outcomes included weight loss (kg) and percent weight loss from baseline and at 12, 24, and 52 weeks. Both completers and intention-to-treat analyses were conducted. Completers' (i.e., those with complete data for 52 weeks) outcomes were evaluated after stratification for reported adherence to the MMRS and ASM. RESULTS: Participants who completed 52 weeks of treatment experienced substantial weight losses at 12 (-9.4+/-5.7 kg), 24 (-12.0+/-8.1 kg), and 52 weeks (-12.4+/-9.2 kg) and all measures were significantly different from baseline weight (p<0.001 for all contrasts) for both true completers (n=324) and for ITT analysis (n=1,351). Fifty percent of patients remained in the program at 24 weeks and nearly 25% were still participating at one year. CONCLUSIONS: This weight loss program using a combination of MMRS and ASM produced significant and sustained weight losses at 52 weeks. Results were better than those typically reported for obesity pharmacotherapy in both short- and long-term studies and also better than those reported for partial meal replacement programs. Program retention at one year was similar to that reported in many controlled drug trials and better than most commercial programs reported in the literature.

Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD).

BACKGROUND: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. PURPOSE: and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. RESULTS: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. LIMITATIONS: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. CONCLUSIONS: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.

Evaluation of a primary care-oriented brief counselling intervention for obesity with and without orlistat.

OBJECTIVE: There is a significant need for an obesity treatment model suitable for the primary care environment. We examined the effectiveness of a brief counselling intervention alone, in combination with orlistat, and drug-alone in a 12-month randomized-clinical trial at a medical school obesity centre. METHODS: Participants (N = 250) with body mass index (BMI) >or=27 were randomized. Changes in body weight, lipids, blood pressure and serum glucose were examined. Drug adherence and attendance were also evaluated. RESULTS: Completers analysis was conducted on 136 participants with data at baseline, 6 and 12 months and intention-to-treat analyses (ITT) for the total sample. Amongst completers, participants in the drug only (P = 0.012) and drug + brief counselling (P = 0.001) groups lost more weight (mean +/- SD: -3.8 +/- 5.8 kg and -4.8 +/- 4.4 kg, respectively) than participants in the brief counselling only group at 6 months (-1.7 +/- 3.3 kg), but there were no significant group differences at 12 months. ITT model results were similar to completers at 6 months and remained significant at 12 months, but the weight losses were more modest (<3 kg) for both groups receiving orlistat. For brief counselling alone, participants gained weight (1.7 +/- 4.2 kg). Cardiovascular disease (CVD) parameter changes were negligible. CONCLUSIONS: Pharmacotherapy alone or combined with brief counselling resulted in modest weight losses that had minimal impact on cardiovascular parameters, but were greater than brief counselling alone. Whilst brief interventions and primary pharmacotherapy have been suggested as viable treatments for implementation in primary care settings, our study suggests that such minimal interventions provide minimal benefits.

Does metabolic syndrome mitigate weight loss in overweight Mexican American women treated for 1-year with orlistat and lifestyle modification?

AIMS: To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle management (OLM) intervention on weight loss in Mexican American women with and without metabolic syndrome (MS). METHODS: One hundred and seven female participants aged 21-65 years and of Mexican origin were randomized to either OLM or a wait-list control group (WLC) for one year. The lifestyle interventions were tailored to exhibit features of the Mexican culture. Within each group, subjects with MS were compared to those without MS to assess whether its presence mitigates weight loss. Risk factors for MS also were assessed. RESULTS: Participants with MS in the OLM group experienced significant decreases in weight and body mass index (BMI) as compared to participants without MS. Participants with MS in the OLM group and who completed the study lost 9.3+/-7.5 kg (20.5+/-16.5 lb) as compared to participants with MS in the WLC group, who only lost 0.2+/-3.1 kg (0.4+/-6.8 lb). Further, participants with MS in the OLM group who completed the study experienced a 3.1+/-3.9 kg/m2 decrease in BMI whereas participants with MS in the WLC group only experienced a 0.1+/-1.2 kg/m2 decrease in BMI. No changes in other MS risk factors were significant. CONCLUSIONS: Patients with MS experienced significant weight loss and decreases in BMI as a result of a lifestyle and pharmacotherapy intervention.

Weight loss with meal replacement and meal replacement plus snacks: a randomized trial.

OBJECTIVE: To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. DESIGN: A prospective 24 week, 2 (snacking vs nonsnacking) x 2 (MR vs meal replacement augmented with snacks (MRPS)) randomized trial. Participants were instructed to limit their total daily intake to 1200 (women) or 1500 (men) kcals. Those receiving the MR program were instructed not to snack while those in the MRPS program were told to snack three times per day. SUBJECTS: A total of 100 participants were block-randomized, based on prestudy snacking status (high vs low), to receive a standard meal replacement program (MR) or MRPS. MEASUREMENTS: Weight, height, blood pressure, lipid fractions, glucose, and insulin were assessed at the baseline, 12-, and 24 weeks. RESULTS: Completers analysis at 24 weeks demonstrated a significant time effect (F(1,46)=44.6, P<0.001), indicating that all participants lost significant amounts of weight regardless of group assignment. An intention-to-treat model resulted in similar results. By week 24, the average weight loss across groups was 4.6 kg. There also were significant improvements across all groups among completers for systolic blood pressure (P=0.047), cholesterol (P=0.001), LDL (P=0.001), glucose (P=0.004), and insulin (P=0.001) at week 12, and glucose (P=0.001) and insulin at week 24 (P=0.003). CONCLUSIONS: Our results suggest that a participant's preferences for snacking did not affect their response to treatment. Snackers and nonsnackers responded equally well whether they received a standard meal replacement program or one augmented with snacks.

Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification.

OBJECTIVE: To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women. SUBJECTS: Mexican-American women (N=108), aged 21-65 y, with a body mass index (BMI) > or =27 kg/m(2) were randomized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention (OLM; n=56) or a wait-list control group (WLC; n=52). DESIGN: A randomized, controlled, open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The OLM intervention included behavior modification, a low-fat (< or =30% of total daily calories) diet, and moderate physical activity (> or =150 min/week). MEASUREMENT: Primary outcomes included changes in body weight (kg), BMI, waist circumference, blood pressure, glucose, and lipids. RESULTS: A total of 72 (37 OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/-0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM-treated patients also experienced significant reductions in waist circumference, low-density-lipoprotein, and total cholesterol. CONCLUSIONS: This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women, a population with substantial risk for obesity.

Psychometric characteristics of the General Well-Being Schedule (GWB) with African-American women.

The General Well-Being Schedule (GWB) is a brief, reliable, and valid instrument used in population studies to assess psychological well-being, although its validity with African-Americans has yet to be established. This study evaluated the reliability, validity, and factor structure of the GWB in a sample of 599 overweight African-American women who participated in multicenter weight loss trial. The results of the factor analysis indicate that the GWB is primarily unidimensional and that the existence of the six hypothesized subscales was not supported. The GWB demonstrated evidence of concurrent and construct validity when examined in association with measures of self-concept, depression, and several health behaviors. The results of this study suggest that the GWB is a reliable and valid measure of psychological well-being in African-American women.

Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials.

AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.

Lifestyle treatments in randomized clinical trials of pharmacotherapies for obesity.

OBJECTIVE: This meta-analysis evaluated the types of lifestyle treatments used in published obesity drug studies and assessed their contribution to weight losses associated with pharmacological interventions. RESEARCH METHODS AND PROCEDURES: Randomized, placebo-controlled, double-blind clinical trials of anti-obesity agents that are/were Food and Drug Administration-approved for the treatment of obesity (both prescription and over-the-counter), and drugs that are Food and Drug Administration-approved and are used off-label for obesity were included. Studies were located by computer searches of databases (e.g., Medline, PsychInfo) and reviewing tables of content/reference sections of journals, abstracts, previous reviews, past empirical studies, relevant book chapters, and recent issues of journals that regularly publish obesity research. In addition, a number of individuals who regularly publish in the obesity literature were asked to provide personal lists of obesity-drug studies. Based on the above criteria, a total of 108 randomized clinical trials were located. RESULTS: Balanced-deficit diets, low-calorie diets, and self-monitoring were the most used lifestyle treatments in published obesity studies. They were incorporated into 40.7%, 25%, and 23.1% of pharmacotherapy studies, respectively. Physical activity and other behavioral or psychotherapeutic interventions rarely were used. A substantial portion of weight loss experienced by patients was attributable to both "placebo effects" and to the lifestyle treatments. DISCUSSION: Obesity-pharmacotherapy trials do not use lifestyle treatments with the frequency expected based on the official positions of most professional organizations concerned with the comprehensive management of obesity.

Evaluation of a culturally appropriate intervention to increase physical activity.

OBJECTIVE: To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women. METHODS: Participants were randomly assigned to a physical activity program or wait-list control. RESULTS: Treated participants were not more active than controls at 6 or 12 months. In addition, we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups. CONCLUSION: The intervention did not increase physical activity in this population. Differences in baseline activity and contamination of the control group may partially account for the outcome.

Blood pressure and symptoms of depression and anxiety: a prospective study.

This study investigated whether symptoms of depression and anxiety were related to the development of elevated blood pressure in initially normotensive adults. The study's hypothesis was addressed with an existing set of prospective data gathered from an age-, sex-, and weight-stratified sample of 508 adults. Four years of follow-up data were analyzed both with logistic analysis, which used hypertension (blood pressure > or =140 mm Hg systolic or 90 mm Hg diastolic) as the dependent variable, and with multiple regression analysis, which used change in blood pressure as the dependent variable. Five physical risk factors for hypertension (age, sex, baseline body mass index, family history of hypertension, and baseline blood pressure levels) were controlled for in the regression analyses. Use of antidepressant/antianxiety and antihypertensive medications were controlled for in the study. Of the 433 normotensive participants who were eligible for our study, 15% had missing data in the logistic regression analysis focusing on depression (n = 371); similarly, 15% of the eligible sample had missing data in the logistic regression using anxiety as the psychological variable of interest (n = 370). Both logistic regression analyses showed no significant relationship for either depression or anxiety in the development of hypertension. The multiple regression analyses (n = 369 for the depression analysis; n = 361 for the anxiety analysis) similarly showed no relationship between either depression or anxiety in changes in blood pressure during the 4-year follow-up. Thus, our results do not support the role of depressive or anxiety symptoms in the development of hypertension in our sample of initially normotensive adults.

Genetic bottlenecks, perceived racism, and hypertension risk among African Americans and first-generation African immigrants.

The complexity of factors influencing the development of hypertension (HTN) in African Americans has given rise to theories suggesting that genetic changes occurred due to selection pressures/genetic bottleneck effects (ie, constriction of existing genetic variability) over the course of the slave trade. Ninety-nine US-born and 86 African-born health professionals were compared in a cross-sectional survey examining genetic and psychosocial predictors of HTN. We examined the distributions of three genetic loci (G-protein, AGT-235, and ACE I/D) that have been associated with increased HTN risk. There were no significant differences between US-born African Americans and African-born immigrants in the studied genetic loci or biological variables (eg, plasma renin and angiotensin converting enzyme activity), except that the AGT-235 homozygous T genotype was somewhat more frequent among African-born participants than US-born African Americans. Only age, body mass index, and birthplace consistently demonstrated associations with HTN status. Thus, there was no evidence of a genetic bottleneck in the loci studied, ie, that US-born African Americans have different genotype distributions that increase their risk for HTN. In fact, some of the genotypic distributions evidenced lower frequencies of HTN-related alleles among US-born African Americans, providing evidence of European admixture. The consistent finding that birthplace (ie, US vs Africa) was associated with HTN, even though it was not always significant, suggests potential and unmeasured cultural, lifestyle, and environmental differences between African immigrants and US-born African Americans that are protective against HTN.

Determining the amount of physical activity needed for long-term weight control.

OBJECTIVE: To evaluate prospectively the influence of habitual physical activity on body weight of men and women and to develop a model that defines the role of physical activity on longitudinal weight change. DESIGN AND SETTING: Occupational cohort study conducted for a mean of 5.5 y. SUBJECTS: A total of 496 (341 male and 155 female) NASA/Johnson Space Center employees who completed the 3 month education component of the employee health-related fitness program and remained involved for a minimum of 2 y. MEASUREMENTS: Body weights were measured at baseline (T1) and follow-up (T2), and habitual physical activity was obtained from the mean of multiple ratings of the 11-point (0-10) NASA Activity Scale (NAS) recorded quarterly between T1 and T2. Other measures included age, gender, VO(2 max) obtained from maximal treadmill testing, body mass index (BMI), and body fat percentage. RESULTS: Multiple regression demonstrated that mean NAS, T1 weight, aging and gender all influence long-term T2 weight. T1 age was significant for the men only. Independently, each increase in mean NAS significantly (P<0.01) reduced T2 weight in men (b=-0.91 kg; 95% CI:-1.4 to-0.42 kg) and women (b=-2.14 kg; 95% CI:-2.93 to-1.35 kg). Mean NAS had a greater effect on T2 weight as T1 weight increased, and the relationship was dose-dependent. CONCLUSIONS: Habitual physical activity is a significant source of long-term weight change. The use of self-reported activity level is helpful in predicting long-term weight changes and may be used by health care professionals when counseling patients about the value of physical activity for weight control.

Nutrient intake of obese female binge eaters.

OBJECTIVE: To compare the 6-month change in selected nutrients and number of binge days (from 7-day food records) between obese binge eaters randomly assigned to either a behavioral self-management (BSM) or waiting list control (WLC) group. Within each of the 2 groups, the average intake of selected nutrients on binge and nonbinge days at baseline and at 6 months were compared. DESIGN: A randomized, controlled, intervention study with assessments at entry and 6 months later. SUBJECTS: Forty-six women in the BSM group and 36 in the WLC group completed the 6-month measurement. Participants were 25 to 50 years of age, 30 to 90 pounds overweight, did not have a history of physical or psychological illnesses, and scored 20 or greater on the binge eating scale. INTERVENTION: Participants in the BSM intervention received 6 months of weekly, 1-hour classes taught by registered dietitians. Participants in the WLC group were not contacted during the 6 months. OUTCOME MEASURES: The main outcome measures were change in energy consumed (kilocalories); percentage of energy from fat, protein, and carbohydrate; grams of fiber/1,000 kcal; and change in the number of self-reported binge days. STATISTICAL ANALYSES: Weight at 6 months was compared using a 2-sample t test. The change in the number of binge days at 6 months and the amount of change in selected nutrients by group was compared using the 2-sample t test. The paired t test was used to compare the average nutrient intakes on binge and nonbinge days within groups. RESULTS: No significant difference was found in the 6-month change between groups in any of the selected nutrients. The BSM group reported a greater reduction in binge days between baseline and 6 months compared with the WLC group (mean 1.0 vs 1.7, P < 0.03). Within the BSM group at 6 months, energy intake and percentage of energy from fat on nonbinge days were significantly reduced compared with binge days. At baseline within the WLC group, energy intake increased and percentage of energy from protein decreased significantly on nonbinge days compared with binge days. Within the WLC group at 6 months, energy intake and percentage of energy from fat significantly decreased and percentage of energy from protein significantly increased on nonbinge days. CONCLUSIONS: Our results suggest that collecting dietary information from participants identified with binge eating disorder is challenging. Dietitians who conduct behavioral weight management programs may require additional training in identifying and understanding the psychological characteristics of participants with binge-eating disorder.

Negative stress and the outcome of treatment for binge eating.

This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress.

Successful management of the obese patient.

Obesity is a chronic disease that affects a substantial number of Americans. Obesity significantly increases a person's risk of cardiovascular diseases and morbidity. Modification of lifestyle behaviors that contribute to obesity (e.g., inappropriate diet and inactivity) is the cornerstone of treatment. Behavior modification involves using such techniques as self-monitoring, stimulus control, cognitive restructuring, stress management and social support to systematically alter obesity-related behaviors. In addition, adjunctive pharmacotherapy can play an important role in the routine medical management of obesity.