Intensive Weight Loss Intervention and Cancer Risk in Adults with Type 2 Diabetes: Analysis of the Look AHEAD Randomized Clinical Trial.

OBJECTIVE: This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. METHODS: Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. RESULTS: After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). CONCLUSIONS: An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

The Contributions of 'Diet', 'Genes', and Physical Activity to the Etiology of Obesity: Contrary Evidence and Consilience.

The debate on the relative contributions of presumptive etiologic factors in the development of obesity is becoming increasingly speculative, insular, and partisan. As the global prevalence of obesity continues to rise, the sheer volume of unfounded conjecture threatens to obscure well-established evidence. We posit that the failure to distinguish between causal factors and mere statistical associations engendered the proliferation of misleading and demonstrably false research programs and failed public health initiatives. Nevertheless, scientific progress necessitates the elimination of unsupported speculation via critical examinations of contrary evidence. Thus, the purpose of this review is to present a concise survey of potentially falsifying evidence for the major presumptive etiologic factors inclusive of 'diet', 'genes', physical activity, and non-physiologic factors from the social sciences. Herein, we advance two 'Fundamental Questions of Obesity' that provide a conceptually clear but challenging constraint on conjecture. First, why would an individual (i.e., human or non-human animal) habitually consume more calories than s/he expends? And second, why would the excess calories be stored predominantly as 'fat' rather than as lean tissue? We posit that the conceptual constraint presented by these questions in concert with the parallel trends in body-mass, adiposity, and metabolic diseases in both human and non-human mammals offer a unique opportunity to refute the oversimplification, causal reductionism, and unrestrained speculation that impede progress. We conclude this review with an attempt at consilience and present two novel paradigms, the 'Metabolic Tipping Point' and the 'Maternal Resources Hypothesis', that offer interdisciplinary explanatory narratives on the etiology of obesity and metabolic diseases across mammalian species.

Effect of Low- Versus High-Intensity Exercise Training on Biomarkers of Inflammation and Endothelial Dysfunction in Adolescents With Obesity: A 6-Month Randomized Exercise Intervention Study.

PURPOSE: To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. METHODS: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m-2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. RESULTS: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL-1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL-1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL-1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL-1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL-1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. CONCLUSIONS: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.

Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study.

Background: Lifestyle interventions have been shown to improve physical function over the short term; however, whether these benefits are sustainable is unknown. The long-term effects of an intensive lifestyle intervention (ILI) on physical function were assessed using a randomized post-test design in the Look AHEAD trial. Methods: Overweight and obese (body mass index ≥ 25 kg/m2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including a 4- and 400-m walk, lower extremity physical performance (expanded Short Physical Performance Battery, SPPBexp), and grip strength approximately 11 years postrandomization and 1.5 years after the intervention was stopped (n = 3,783). Results: Individuals randomized to ILI had lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019 [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001, respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005) compared to those randomized to DSE. The intervention effect was slightly larger for SPPBexp scores among older versus younger participants (0.081 [0.038 to 0.124] vs 0.013 [-0.021 to 0.047], p = .01). Conclusions: An intensive lifestyle intervention has modest but significant long-term benefits on physical function in overweight and obese middle-aged and older adults with type 2 diabetes. ClinicalTrials.gov Identifier: NCT00017953.

Effects of a psychological intervention on the quality of life of obese adolescents under a multidisciplinary treatment / Efeitos de uma intervenção psicológica sobre a qualidade de vida de adolescentes obesos em tratamento multidisciplinar

Abstract Objective: To investigate the effects of multidisciplinary treatment with and without psychological counseling on obese adolescents' self-reported quality of life. Methods: Seventy-six obese adolescents (15.87 ± 1.53 y) were allocated into psychological counseling group (PCG; n = 36) or control group (CG; n = 40) for 12 weeks. All participants received the same supervised exercise training, nutritional and clinical counseling. Participants in PCG also received psychological counseling. QOL was measured before and after 12 weeks of intervention by Generic Questionnaire for the Evaluation of Quality of Life (SF-36). Results: The dropout rate was higher in GC (22.5%) when compared with PCG (0.0%) (p < 0.001). After 12 weeks, participants from PCG presents lower body weight, relative fat mass and higher free fat mass (p < 0.001 for all) compared to GC. QOL improved among adolescents from both groups (p < 0.05), however, a better QOL was reported from those adolescents enrolled in PCG. Conclusion: The inclusion of a psychological counseling component in multidisciplinary treatment for adolescent obesity appears to provide benefits observed for improved QOL as compared with treatment without psychological counseling.

Resumo Objetivo: Investigar os efeitos do tratamento multidisciplinar com e sem aconselhamento psicológico voltado para a qualidade de vida de adolescentes obesos. Métodos: Foram alocados 76 adolescentes obesos (15,87 ± 1,53 ano) em um grupo de aconselhamento psicológico (GAP; n = 36) e um grupo de controle (GC; n = 40) por 12 semanas. Todos receberam o mesmo treinamento físico supervisionado e aconselhamento nutricional e clínico. Os participantes no GAP também receberam aconselhamento psicológico. A qualidade de vida foi avaliada antes e depois das 12 semanas de intervenção por meio do Questionário Genérico de Avaliação da Qualidade de Vida (SF-36). Resultados: O abandono do tratamento foi maior no GC (22,5%) em comparação com o GAP (0,0%) (p < 0,001). Após 12 semanas, os participantes do GAP apresentam menor peso corporal, massa gorda relativa e maior massa livre de gordura (p < 0,001 para todos) em comparação com o GC. A qualidade de vida melhorou entre os adolescentes de ambos os grupos (p < 0,05); contudo, uma melhor qualidade de vida foi relatada pelos adolescentes incluídos no GAP. Conclusão: A inclusão de aconselhamento psicológico no tratamento multidisciplinar dos adolescentes obesos parece proporcionar benefícios observados na melhoria da qualidade de vida, em comparação com o tratamento sem aconselhamento psicológico.

Low levels of physical activity are associated with dysregulation of energy intake and fat mass gain over 1 year.

BACKGROUND: Previous studies suggest that appetite may be dysregulated at low levels of activity, creating an energy imbalance that results in weight gain. OBJECTIVE: The aim was to examine the relation between energy intake, physical activity, appetite, and weight gain during a 1-y follow-up period in a large sample of adults. DESIGN: Participants included 421 individuals (mean ± SD age: 27.6 ± 3.8 y). Measurements included the following: energy intake with the use of interviewer-administered dietary recalls and calculated by using changes in body composition and energy expenditure, moderate-to-vigorous physical activity (MVPA) with the use of an arm-based monitor, body composition with the use of dual-energy X-ray absorptiometry, and questionnaire-derived perceptions of dietary restraint, disinhibition, hunger, and control of eating. Participants were grouped at baseline into quintiles of MVPA (min/d) by sex. Measurements were repeated every 3 mo for 1 y. RESULTS: At baseline, an inverse relation existed between body weight and activity groups, with the least-active group (15.7 ± 9.9 min MVPA/d, 6062 ± 1778 steps/d) having the highest body weight (86.3 ± 13.2 kg) and the most-active group (174.5 ± 60.5 min MVPA/d, 10260 ± 3087 steps/d) having the lowest body weight (67.5 ± 11.0 kg). A positive relation was observed between calculated energy intake and activity group, except in the lowest quintile of activity. The lowest physical activity group reported higher levels of disinhibition (P = 0.07) and cravings for savory foods (P = 0.03) compared with the group with the highest level of physical activity. Over 1 y of follow-up, the lowest activity group gained the largest amount of fat mass (1.7 ± 0.3 kg) after adjustment for change in MVPA and baseline fat mass. The odds of gaining >3% of fat mass were between 1.8 and 3.8 times as high for individuals in the least-active group as for those in the middle activity group. CONCLUSIONS: These results suggest that low levels of physical activity are a risk factor for fat mass gain. In the current sample, a threshold for achieving energy balance occurred at an activity level corresponding to 7116 steps/d, an amount achievable by most adults. This trial was registered at clinicaltrials.gov as NCT01746186.

Predictors of meeting physical activity and fruit and vegetable recommendations in 9-11-year-old children.

OBJECTIVE: Childhood obesity represents a significant public health problem. This study examined physical activity and nutrition behaviours and attitudes of 9-11-year-olds, and factors influencing these behaviours. DESIGN: Study participants recorded pedometer steps for 7 days and completed physical activity enjoyment, food attitudes and food frequency questionnaires. Fruit and vegetable sales data were collected from schools. The setting for the study was elementary schools in metropolitan Denver, Colorado (USA). METHOD: Logistic regression was used to determine significant predictors of meeting physical activity/fruit and vegetable intake recommendations. RESULTS: Overall, 42.0% of boys and 44.1% of girls met step count recommendations. Further, 30.9% of boys and 32.8% of girls met step count requirements associated with low risk for overweight/obesity. Enjoyment of physical activity significantly predicted achieving recommendations. Overall, 66.4%, 51.3% and 65.8% of 9-11-year-olds achieved adequate fruit, vegetable, or fruit and vegetable intake, respectively. Enjoyment of fruit/vegetable consumption, perceived parental intake and encouragement and cups of vegetables purchased predicted achieving adequate intake. CONCLUSION: The majority of young people aged 9-11 years failed to meet step count recommendations to prevent the risk for overweight/obesity. A significant proportion also failed to achieve adequate fruit and/or vegetable intake. Future programmes and interventions should affect multiple environments in order to improve child enjoyment of physical activity and fruit/vegetable intake in order to improve the physical, mental and emotional health of children.

Home-schooled children are thinner, leaner, and report better diets relative to traditionally schooled children.

OBJECTIVE: To examine and compare the relationships among diet, physical activity, and adiposity between home-schooled children (HSC) and traditionally schooled children (TSC). DESIGN AND METHODS: Subjects were HSC (n = 47) and TSC (n = 48) aged 7-12 years old. Dietary intakes were determined via two 24-h recalls and physical activity was assessed with 7 days of accelerometry. Fat mass (FM), trunk fat, and percent body fat (%BF) were measured by dual-energy X-ray absorptiometry (DXA). RESULTS: Relative to HSC, TSC demonstrated significantly higher BMI percentiles, FM, trunk fat, and %BF; consumed 120 total kilocalories more per day; and reported increased intakes of trans fats, total sugar, added sugars, calcium, and lower intakes of fiber, fruits, and vegetables (P < 0.05). At lunch, TSC consumed significantly more calories, sugar, sodium, potassium, and calcium compared to HSC (P < 0.05). Physical activity did not differ between groups. Traditional schooling was associated with increased consumption of trans fat, sugar, calcium (P < 0.05); lower intakes of fiber, and fruits and vegetables (P < 0.05); and higher FM, %BF, and trunk fat (P < 0.01), after adjustment for covariates. CONCLUSIONS: These data suggest HSC may consume diets that differ in energy and nutrient density relative to TSC, potentially contributing to differences in weight and adiposity.

Readiness redefined: a behavioral task during screening predicted 1-year weight loss in the look AHEAD study.

OBJECTIVE: Predicting outcome in weight loss trials from baseline characteristics has proved difficult. Readiness to change is typically measured by self-report. METHODS: Performance of a behavioral task, completion of food records, from the screening period in the Look AHEAD study (n = 549 at four clinical centers) was assessed. Completeness of records was measured by the number of words and Arabic numerals (numbers) recorded per day, the number of eating episodes per day, and days per week where physical activity was noted. The primary outcome was weight loss at one year. RESULTS: In univariable analysis, both the number of words recorded and the number of numbers recorded were associated with greater weight loss. In multivariable analysis, individuals who recorded 20-26, 27-33, and ≥34 words per day lost 9.12%, 11.40%, and 12.08% of initial weight, compared to 8.98% for individuals who recorded less than 20 words per day (P values of 0.87, 0.008, and <0.001, respectively, compared to <20 words per day). CONCLUSIONS: Participants who kept more detailed food records at screening lost more weight after 1 year than individuals who kept sparser records. The use of objective behavioral screening tools may improve the assessment of weight loss readiness.

Weight-loss maintenance for 10 years in the National Weight Control Registry.

BACKGROUND: The challenge of weight-loss maintenance is well known, but few studies have followed successful weight losers over an extended period or evaluated the effect of behavior change on weight trajectories. PURPOSE: To study the weight-loss trajectories of successful weight losers in the National Weight Control Registry (NWCR) over a 10-year period, and to evaluate the effect of behavior change on weight-loss trajectories. METHODS: A 10-year observational study of self-reported weight loss and behavior change in 2886 participants (78% female; mean age 48 years) in the NWCR who at entry had lost at least 30 lbs (13.6 kg) and kept it off for at least one year. Data were collected in 1993-2010; analysis was conducted in 2012. MAIN OUTCOME MEASURES: Weight loss (kilograms; percent weight loss from maximum weight). RESULTS: Mean weight loss was 31.3 kg (95% CI=30.8, 31.9) at baseline, 23.8 kg (95% CI=23.2, 24.4) at 5 years and 23.1±0.4 kg (95% CI=22.3, 23.9) at 10 years. More than 87% of participants were estimated to be still maintaining at least a 10% weight loss at Years 5 and 10. Larger initial weight losses and longer duration of maintenance were associated with better long-term outcomes. Decreases in leisure-time physical activity, dietary restraint, and frequency of self-weighing and increases in percentage of energy intake from fat and disinhibition were associated with greater weight regain. CONCLUSIONS: The majority of weight lost by NWCR members is maintained over 10 years. Long-term weight-loss maintenance is possible and requires sustained behavior change.

Public-private partnerships: the evolving role of industry funding in nutrition research.

The global burdens of morbidity and mortality associated with obesity-related chronic diseases are crippling public health and are predicted to exponentially increase over the next 3 decades. Meanwhile, the resources necessary to conduct research that may offer solutions to the obesity epidemic continue to decline and funding has become increasingly difficult to secure. Alternative models for funding nutrition and health research are necessary to make considerable and timely progress to improve public health. Key stakeholders include, but are not limited to, government agencies, foundations, private industry, and nongovernmental organizations.

High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase.

UNLABELLED: Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with a high-fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild-type or fructokinase knockout mice were fed a low-fat (11%), high-fat (36%), or high-fat (36%) and high-sucrose (30%) diet for 15 weeks. Both wild-type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence of hepatic inflammation on a high-fat diet compared to a low-fat diet. In contrast, wild-type mice fed a high-fat and high-sucrose diet developed more severe hepatic steatosis with low-grade inflammation and fibrosis, as noted by increased CD68, tumor necrosis factor alpha, monocyte chemoattractant protein-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. CONCLUSION: An additive effect of high-fat and high-sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high-fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis.

'Small changes' to diet and physical activity behaviors for weight management.

Obesity is associated with numerous short- and long-term health consequences. Low levels of physical activity and poor dietary habits are consistent with an increased risk of obesity in an obesogenic environment. Relatively little research has investigated associations between eating and activity behaviors by using a systems biology approach and by considering the dynamics of the energy balance concept. A significant body of research indicates that a small positive energy balance over time is sufficient to cause weight gain in many individuals. In contrast, small changes in nutrition and physical activity behaviors can prevent weight gain. In the context of weight management, it may be more feasible for most people to make small compared to large short-term changes in diet and activity. This paper presents a case for the use of small and incremental changes in diet and physical activity for improved weight management in the context of a toxic obesogenic environment.

The association of self-reported sleep, weight status, and academic performance in fifth-grade students.

BACKGROUND: To improve support and justification for health promotion efforts in schools, it is helpful to understand how students' health behaviors affect academic performance. METHODS: Fifth-grade students completed an online school-administered health survey with questions regarding their eating behavior, physical activity, academic performance, and sleep patterns. Differences in health behaviors were examined by sex, self-reported weight status, and sufficient (≥9 hours) versus insufficient sleep. Logistic regression was used to determine the relationship between academic performance and the health behaviors. RESULTS: One third of the sample did not get the recommended amount of physical activity and more than half of the students watched television ≥ 2 hours/day. Self-reported overweight status was related to lower self-reported academic performance, fewer lunch and breakfast occasions, less physical activity, not meeting the recommendations for vegetable and soda consumption as well as hours of television watching. Sufficient sleep (≥9 hours/night) was associated with better grades, meeting the recommended hours of daily television watching and video game playing, being more physically active and increased breakfast and lunch frequency. Percentage of serving free/reduced lunch, soda consumption, breakfast frequency, amount of physical activity, and television watching were associated with academic performance. CONCLUSION: More positive health behaviors generally were associated with better academic performance. Promoting healthy behaviors in schools might improve not only students' health academic performance as well.

Energy balance: the key to a unified message on diet and physical activity.

The aim of this commentary is to highlight the advantages of an energy-balance framework to unify diet and physical activity messages. Despite an array of pharmacotherapies, lifestyle modification remains the first-line approach for preventing obesity, cardiometabolic diseases, and cancer. Yet, patients, let alone professionals, often perceive recommendations on diet to be separate from, or even competitive with, those on physical activity. They perceive these as 2 sets of unrelated guidelines. This is a mistaken and unfortunate view. Nutrition and physical activity are highly interrelated, complementary, and synergistic. As exemplified by findings from the National Weight Control Registry, the power of combining a wise diet and a physically active lifestyle is compelling. Accordingly, the American Cancer Society and the American Heart Association have integrated their respective diet/physical activity/body weight recommendations into single documents. Corresponding follow-through at the clinical level is overdue. The diet versus physical activity question is passé. Let us move forward by teaching our patients about energy balance, the inclusive concept that captures the synergy between diet and physical activity. Adopting an energy-balance framework can improve the relevancy and potency of lifestyle messages to patients and better enable them to develop and apply effective behavior-change skills.

Comparative effects of low-carbohydrate high-protein versus low-fat diets on the kidney.

BACKGROUND AND OBJECTIVES: Concerns exist about deleterious renal effects of low-carbohydrate high-protein weight loss diets. This issue was addressed in a secondary analysis of a parallel randomized, controlled long-term trial. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Between 2003 and 2007, 307 obese adults without serious medical illnesses at three United States academic centers were randomly assigned to a low-carbohydrate high-protein or a low-fat weight-loss diet for 24 months. Main outcomes included renal filtration (GFR) indices (serum creatinine, cystatin C, creatinine clearance); 24-hour urinary volume; albumin; calcium excretion; and serum solutes at 3, 12, and 24 months. RESULTS: Compared with the low-fat diet, low-carbohydrate high-protein consumption was associated with minor reductions in serum creatinine (relative difference, -4.2%) and cystatin C (-8.4%) at 3 months and relative increases in creatinine clearance at 3 (15.8 ml/min) and 12 (20.8 ml/min) months; serum urea at 3 (14.4%), 12 (9.0%), and 24 (8.2%) months; and 24-hour urinary volume at 12 (438 ml) and 24 (268 ml) months. Urinary calcium excretion increased at 3 (36.1%) and 12 (35.7%) months without changes in bone density or clinical presentations of new kidney stones. CONCLUSIONS: In healthy obese individuals, a low-carbohydrate high-protein weight-loss diet over 2 years was not associated with noticeably harmful effects on GFR, albuminuria, or fluid and electrolyte balance compared with a low-fat diet. Further follow-up is needed to determine even longer-term effects on kidney function.

Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

Obesity: overview of an epidemic.

The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates of obesity. We need a successful model that will help us understand what to do to address obesity. A good example is the recent HEALTHY study. This comprehensive intervention was implemented in several schools and aimed to reduce obesity by concentrating on behavior and environment. This intervention delivered most of the strategies we believe to be effective in schools. Although the program produced a reduction in obesity, this reduction was not greater than the reduction seen in the control schools that did not receive the intervention. This does not mean we should not be intervening in schools, but rather that it may require concerted efforts across behavioral settings to reduce obesity. Although we need successful models, there is a great deal of urgency in responding to the obesity epidemic. An excellent example is the effort to get menu labeling in restaurants, which is moving rapidly toward being national policy. The evaluation of this strategy is still ongoing, and it is not clear what impact it will have on obesity rates. We should be encouraging efforts like this, but we must evaluate them rigorously. Once we become serious about addressing obesity, it will likely take decades to reverse obesity rates to levels seen 30 years ago. Meanwhile, the prevalence of overweight and obesity remains high and quite likely will continue to increase.

Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial.

This 56-week, randomized, placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m²) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained-release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions. Co-primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent-to-treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.