First-line Treatment For Obesity Research Articles

Research progresses on interventions of obesity in children and adolescents

Childhood and adolescent obesity has become a global epidemic. The interventions mainly include lifestyle intervention, medication treatment and bariatric surgery. Among them, lifestyle intervention, especially intensive lifestyle intervention with participation of family members, is the first-line treatment for obesity in children and adolescents. Both medication and bariatric surgery are adjuvant treatments for severely obese children and adolescents. Currently, metformin is the most widely used drug for the treatment of obesity in children and adolescents in both China and other countries; orlistat and liraglutide are also the drugs that are safe and often used in other countries; other drugs are not recommended. As a tertiary prevention and treatment strategy for obesity, bariatric surgery should be carried out on the basis of good compliance from both the children and their family members, with the cooperation of multiple disciplines. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most common types of procedure performed. Meanwhile, as a new treatment method, intra-gastric balloon procedure needs to be paid more attention to its efficacy and safety.

Weight Loss Strategies.

Lifestyle interventions for weight loss combine support for changing diet and physical activity with weight management education and are considered the first line treatment for obesity. A variety of diet-focused interventions including time-restricted eating are also increasingly being promoted for weight management. This chapter reviews different types of interventions for weight management, their underlying health behavior change models, and effectiveness to date in randomized trials. The results justify increasing efforts to improve program effectiveness generally, and to personalize interventions to support long-term adherence. The high prevalence of obesity worldwide, combined with the known increase in risk of non-communicable diseases with duration of excess weight, provides a compelling justification for routine delivery of effective weight management interventions in the community and in clinical care.

Randomized trial of a novel lifestyle intervention compared with the Diabetes Prevention Program for weight loss in adult dependents of military service members

Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low. We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity. Participants were randomly assigned to HWL (n=121) or m-DPP (n=117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models. Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P=0.30). Mean±SE adjusted 12-mo weight loss in the ITT cohort was 7.46±0.85 kg for HWL and 7.32±0.87 kg for m-DPP (P=0.91); in the CC cohort, it was 7.83±0.82 kg for HWL and 6.86±0.88 kg for m-DPP (P=0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P=0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P=0.05 to <0.001 for ITT). HWL and m-DPP showed equivalent and clinically impactful mean weight loss with cardiometabolic benefits. These results identify an alternative approach for behavioral treatment of overweight and obesity.This trial was registered at clinicaltrials.gov as NCT02348853.

Diets Varying in Carbohydrate Content Differentially Alter Brain Activity in Homeostatic and Reward Regions in Adults.

Obesity has one of the highest refractory rates of all chronic diseases, in part because weight loss induced by calorie restriction, the first-line treatment for obesity, elicits biological adaptations that promote weight regain. Although acute feeding trials suggest a role for macronutrient composition in modifying brain activity related to hunger and satiety, relevance of these findings to weight-loss maintenance has not been studied. We investigated effects of weight-loss maintenance diets varying in macronutrient content on regional cerebral blood flow (rCBF) in brain regions involved in hunger and reward. In conjunction with a randomized controlled feeding trial, we investigated the effects of weight-loss maintenance diets varying in carbohydrate content [high, 60% of total energy: n=20; 6 men/14 women; mean age: 32.5 y; mean BMI (in kg/m 2): 27.4; moderate, 40% of total energy: n=22; 10 men/12 women; mean age: 32.5 y; mean BMI: 29.0; low, 20% of total energy: n=28; 12 men/16 women; mean age: 33.2 y; mean BMI: 27.7] on rCBF in brain regions involved in hunger and reward preprandial and 4 h postprandial after 14-20 wk on the diets. The primary outcome was rCBF in the nucleus accumbens (NAcc) at 4 h postprandial; the secondary outcome was preprandial rCBF in the hypothalamus. Consistent with a priori hypothesis, at 4 h postprandial, NAcc rCBF was 43% higher in adults assigned to the high- compared with low-carbohydrate diet {P[family-wise error (FWE)-corrected]<0.05}. Preprandial hypothalamus rCBF was 41% higher on high-carbohydrate diet [P(FWE-corrected)<0.001]. Exploratory analyses revealed that elevated rCBF on high-carbohydrate diet was not specific to prandial state: preprandial NAcc rCBF [P(FWE-corrected)<0.001] and 4 h postprandial rCBF in hypothalamus [P(FWE-corrected)<0.001]. Insulin secretion predicted differential postprandial activation of the NAcc by diet. We report significant differences in rCBF in adults assigned to diets varying in carbohydrate content for several months, which appear to be partially associated with insulin secretion. These findings suggest that chronic intake of a high-carbohydrate diet may affect brain reward and homeostatic activity in ways that could impede weight-loss maintenance. This trial was registered at clinicaltrials.gov as NCT02300857.

Experiences and perceptions of dietitians for obesity management: a general practice qualitative study.

Multi-component lifestyle interventions are the first line treatment for obesity. Dietitians are ideally placed healthcare professionals to deliver such interventions. However, only a small proportion of patients with obesity are referred by general practice to dietitians, and the reasons for this are not clear. The present study aimed to explore general practice healthcare professionals' (GPHCPs) experiences and perceptions of dietitians in the context of obesity management. A convenience sample of GPHCPs practicing in the UK was recruited via a targeted social media strategy, using virtual snowball sampling. Data were collected using semi-structured interviews and analysed using framework analysis. In total, 20 participants were interviewed (11 general practice nurses and nine general practitioners). Experiences of referring patients with obesity for dietetic intervention resulted in two main themes: (i) access barriers and (ii) the dietetic consult experience. Three themes emerged from participants' perceptions of a role for general practice dietitians: (i) utilising dietetic expertise; (ii) access to dietitian; and (iii) time. Participants experienced barriers to accessing dietitians for obesity management and felt that having a dietitian working within their general practice team would help address this. Having a dietitian embedded within their general practice team was perceived to have the potential to alleviate GPHCPs' clinical time pressures, offer opportunities for upskilling, and may improve patient engagement with obesity management. GPHCPs perceived that embedding a dietitian within their general practice team would be valuable and beneficial for obesity management. Our findings provide support for the funding of general practice dietitian roles in the UK.

Evaluation of intervention components to maximize outcomes of behavioral obesity treatment delivered online: A factorial experiment following the multiphase optimization strategy framework

BackgroundBehavioral lifestyle intervention (BLI) is recommended as a first-line treatment for obesity. While BLI has been adapted for online delivery to improve potential for dissemination while reducing costs and barriers to access, weight losses are typically inferior to gold standard treatment delivered in-person. It is therefore important to refine and optimize online BLI in order to improve the proportion of individuals who achieve a minimum clinically significant weight loss and mean weight loss. Study designFive experimental intervention components will be tested as adjuncts to an established 12-month online BLI: virtual reality for BLI skills training, interactive video feedback, tailored intervention to promote physical activity, skills for dysregulated eating, and social support combined with friendly competition. Following the Multiphase Optimization Strategy (MOST) framework, the components will first be refined and finalized during Preparation Phase pilot testing and then evaluated in a factorial experiment with 384 adults with overweight or obesity. A priori optimization criteria that balance efficacy and efficiency will be used to create a finalized treatment package that produces the best weight loss outcomes with the fewest intervention components. Mediation analysis will be conducted to test hypothesized mechanisms of action and a moderator analysis will be conducted to understand for whom and under what circumstances the interventions are effective. ConclusionThis study will provide important information about intervention strategies that are useful for improving outcomes of online BLI. The finalized treatment package will be suitable for testing in a future randomized trial in the MOST Evaluation Phase.

Forever-Fit Summer Camp: The Impact of a Six-Week Summer Healthy Lifestyle Day Camp on Anthropometric, Cardiovascular, and Physical Fitness Measures in Youth with Obesity

Purpose: Pediatric obesity is a grave public health concern with both genetic and environmental risk factors. The first line treatment for obesity in youth is lifestyle intervention, which has proven to be challenging. Forever-Fit Summer Camp (FFSC) is a six-week summer day program that offers physical activity and nutrition education, as well as well-balanced meals and snacks, to youth at low cost. The aim of the study was to assess the impact of FFSC on BMI, cardiovascular and …

Obesity-Related Perivascular Adipose Tissue Damage Is Reversed by Sustained Weight Loss in the Rat

Perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists, and this is lost in obesity. A recent study reported that bariatric surgery reverses the damaging effects of obesity on PVAT function. However, PVAT function has not been characterized after weight loss induced by caloric restriction, which is often the first line treatment for obesity. Contractility studies were performed using wire myography on small mesenteric arteries with and without PVAT from control, diet-induced obese, calorie restricted and sustained weight loss rats. Changes in the PVAT environment were assessed using immunohistochemistry. PVAT from healthy animals elicited an anticontractile effect in response to norepinephrine. This was abolished in diet-induced obesity through a mechanism involving increased local tumor necrosis factor-α and reduced nitric oxide bioavailability within PVAT. Sustained weight loss led to improvement in PVAT function associated with restoration of adipocyte size, reduced tumor necrosis factor-α, and increased nitric oxide synthase function. This was associated with reversal of obesity-induced hypertension and normalization of plasma adipokine levels, including leptin and insulin. We have shown that diet-induced weight loss reverses obesity-induced PVAT damage through a mechanism involving reduced inflammation and increased nitric oxide synthase activity within PVAT. These data reveal inflammation and nitric oxide synthase, particularly endothelial nitric oxide synthase, as potential targets for the treatment of PVAT dysfunction associated with obesity and metabolic syndrome.

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial.

BackgroundClinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk.Methods/DesignSixty women, aged 18–50 years with a body mass index (BMI) greater than 34.9 kg.m2 and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months.DiscussionPrevious research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12611000694910). Date registered: 4 July 2011

202 Obesity-related Perivascular Adipose Tissue Damage is not Completely Reversed following Diet-induced Weight Loss

ObjectivePerivascular adipose tissue (PVAT) exerts an anticontractile effect that is lost in obesity. A recent study reported that bariatric surgery can reverse the damaging effects of obesity on PVAT function...

New pharmacological treatments for the management of obesity.

Obesity is quickly becoming the leading preventable cause of death in the USA. Over 60 obesity-related comorbidities exist which increase the complexity and cost of medical care in obese patients. Even a moderate weight loss of 5% can reduce morbidity associated with these conditions. Lifestyle modification through caloric restriction and enhanced exercise and physical activity remain the first line treatment for obesity. The development of pharmacologic agents for the treatment of obesity has been challenged by both lack of efficacy and serious adverse side effects leading to their removal from market. Two new agents were recently approved by the US Food and Drug Administration to complement lifestyle modification in obese (BMI ≥30kg/m(2)) and overweight patients (BMI ≥27kg/m(2) and one obesity-related comorbidity). Lorcaserin is a novel serotonin 5-HT2C selective agonist which has been shown in three phase III studies to significantly reduce weight and cardiovascular risk factors such as diabetes. Phentermine/topiramate extended release (ER) is a novel combination of two agents which have individually been shown to significantly reduce weight. The combination agent phentermine/topiramate ER has been shown to reduce weight in overweight and obese subjects in a number of studies. This article reviews the pharmacology, clinical efficacy, and safety of these new agents compared to past and other presently available medications for the treatment of obesity.

Pharmacotherapy for obesity

Due to its serious comorbidities and high prevalence, obesity is one of the heaviest burdens for public health. Although diet, exercise and behavioral modification are the first-line treatment for obesity, their outcomes are not satisfactory. The goal of this article is to review currently available anti-obesity drugs so that physicians may apply the principle of pharmacologic treatment for obesity to obese patients in the real clinical situation. Orlistat, phentermine, diethylpropion, mazindol, and phendimetrazine have been approved as anti-obesity drugs by Korea food and drug administration and administered to patients in Korea. Besides, several non-approved drugs, including fluoxetine, bupropion, topiramate and zonisamide, are being used for weight reduction. Among these drugs, orlistat has been studied most and is the only approved drug for long-term weight management. On the other hand, the rest of the approved drugs lack the evidence of safety issues on the long-term administration. Considering that the non-approved drugs have only a small body of clinical trial results for their efficacy and safety as anti-obesity drugs, it is not appropriate to use them as a first-line therapy in obesity. Because several new medicines and combination therapies are under investigations, more drug therapy options seem to be available in this field in coming years. Although the properly executed pharmacologic treatment is a good option for weight reduction, physicians should recognize that diet, exercise, and behavioral modification are essential to all obese patient and that pharmacologic treatment has several limitations until now.

Overview of Emerging Concepts in Metabolic Surgery

Michel Murr, MD, FACS Arash Rafiei, MD Habib Ajami, MD Tannous K Fakhry, MD Introduction There is now a worldwide epidemic of obesity. According to the Centers for Disease Control and Prevention, the prevalence of obesity among all age groups has increased significantly since 1990; about two-thirds of US adults are overweight or obese. Obesity is classified according to body mass index (BMI); overweight is a BMI of 25 to 29.9 kg/m, class I obesity is a BMI of 30 to 34.9 kg/m, class II obesity is a BMI of 35 to 39.9 kg/m, and class III obesity is a BMI of ≥40 kg/m. The 1998 National Heart, Lung, and Blood Institute guidelines recommended a combination of low-calorie diet, exercise, and behavioral therapy as first-line treatment for obesity. Such a comprehensive approach results in weight loss of 8% to 10%; nonetheless, weight regain is common after two years. Metabolic or bariatric surgery induces durable and sustainable weight loss. The 1991 National Institutes of Health Consensus Conference Statement defined the criteria for bariatric surgery as a BMI of ≥40 kg/m or of ≥35 kg/m with comorbidities (Tables 1 and 2). The most recent guidelines of the American Diabetes Association state that “bariatric surgery should be considered for adults with BMI >35 kg/m and type 2 diabetes, especially if the diabetes is difficult to control with lifestyle modification and pharmacologic therapy.” Surgical candidates must have tried other weight-loss modalities (diet, exercise, etc) before consideration of bariatric surgery. It is estimated that about 3% of the US population, or approximately five million people, meet the weight criteria for bariatric surgery. The prevalence of serious comorbidities such as metabolic syndrome is 39% among patients undergoing bariatric surgery. More importantly, among individuals with type 2 diabetes, 85% are overweight and 55% are obese. The Nurses’ Health Study demonstrated that individuals with a BMI of 35 kg/m had a 40-fold increase in their likelihood of developing diabetes. The link between diabetes and obesity is due to induction of insulin resistance by excess adipose tissue and generalized low chronic inflammation. The role of metabolic surgery in the treatment of obesity is well established. The Swedish Obese Subjects (SOS) study demonstrated that metabolic surgery induces remission of diabetes in 69% of obese-diabetic patients. Furthermore, in a meta-analysis of 136 studies, the proportion of patients who had diabetes before surgery (median, 11%; range, 3%–100%) and who showed fewer effects from or resolution of diabetes after surgery ranged from 64% to 100% (median, 100%). Improvements in insulin sensitivity within the first few days after Roux-en-Y gastric bypass (RYGB), before any measurable weight loss, is commonly observed, and has been maintained at

Weight Loss in Obesity and Metabolic Syndrome

Obesity is a chronic problem affecting an increasing number of people worldwide and is now recognized as a global epidemic. Various factors involved in the complex genetic-environmental interactions that cause obesity will promote long-term positive energy balance. A cluster of environmental factors, including high energy intakes in the diet, low energy expenditure, and disturbed substrate oxidation, favour the increase and unfavourable distribution of fat mass. Obesity is a major risk factor for hypertension, cardiovascular disease development and diabetes mellitus, and represents a growing worldwide health problem. Several epidemiological studies have shown a high prevalence of cardiovascular complications and mortality in obesity and metabolic syndrome, type-2 diabetes or hypertension. For at “risk populations” predisposed to target organ damage, stringent targets for blood pressure control, dyslipidaemia, and glycaemia have been set in clinical guidelines, however clinical trial and real-life evidence suggest that these targets are difficult to achieve and sustain. The first line treatment for obesity, and obesity related conditions is weight loss. Life-style modification including low caloric diet, reducing sedentary behaviour and increasing exercise form the basis of all therapy, with more severe obesity pharmacotherapy or bariatric (weight loss) surgery may be indicated. Maintaining weight loss is often the greatest challenge. We review the effect of weight loss, using life-style modifications or bariatric surgery in obese subjects, on obesity-related hypertension, the metabolic syndrome, and some of the putative neurohormonal changes that drive obesity related disease.

Neuroadrenergic dysfunction in obesity: an overview of the effects of weight loss

The prevalence of obesity is rising to epidemic proportions worldwide, and in tandem so is that of type 2 diabetes. Neuroadrenergic abnormalities, comprising increased resting sympathetic nervous system activity and blunted sympathetic neural responsiveness are recognized features of metabolic syndrome obesity, which contribute importantly to both the pathophysiology and adverse clinical prognosis of this high-risk population. Weight loss is recommended as first-line treatment for obesity. This review examines the effects of nonpharmacological weight loss on sympathetic nervous system function under basal and stimulated conditions. Human weight loss trials show that even moderate weight reduction is accompanied by significant attenuation in resting whole-body norepinephrine spillover rate and muscle sympathetic nerve activity, an improvement in cardiac autonomic modulation, and a reversal of blunted sympathetic responsiveness at both peripheral and central nervous system levels. Recent findings underscore the relevance of insulin resistance in mediating blunted sympathetic responsiveness to endogenous hyperinsulinemia induced by glucose ingestion. Impaired insulin transport across the blood-brain barrier may be one mechanism mediating these effects. Weight loss reverses blunted sympathetic responsiveness to glucose, which has implications for postprandial energy expenditure and body weight homeostasis. The autonomic dysfunction of obesity is reversible with weight loss, highlighting the importance of lifestyle intervention as a key therapeutic modality.

Benchmarking Best Practices in Weight Loss Surgery

Benchmarking Best Practices in Weight Loss Surgery

The “Senobi” breathing exercise is recommended as first line treatment for obesity

Neuroadrenergic abnormalities, including a predominant activity of parasympathetic nerve and blunted hormone secretion, are recognized in the overweight patients. This study aimed to examine whether the "Senobi" breathing method, a stretch-breathing exercise that we have developed, could activate or recover sympathetic nervous system activity that leads to the loss of body weight. Forty pre-menopausal women, aged 40 to 50 years, participated in this study. Twenty were healthy and the other 20 were overweight (body mass index>25 and body fat>30%). Sympathetic nerve activity was assessed using equipment that analyzes cardiac-beat variation, and several urinary hormone levels were examined before and 30 min after performing the "Senobi" breathing exercise. The average proportion of sympathetic nerve among healthy women during daytime hours (10:00 AM to 12:00 PM) was 62.6%±2.6%. On the other hand, that of overweight women was 33.5%±0.4%. After 1 min of the "Senobi" breathing, substantial up-regulation of sympathetic nerve activity and increased urinary hormone secretion were observed in the overweight women but not in the healthy controls. Moreover, after repeating the exercise for a month, the obese patients showed significant loss of body fat. The "Senobi" breathing exercise was found to be effective for weight loss in obesity possibly by regulating the autonomic nervous system and the hormone secretion.

Effect of Insulin Resistance, Dyslipidemia, and Intra-abdominal Adiposity on the Development of Cardiovascular Disease and Diabetes Mellitus

Abdominal obesity contributes to insulin resistance, a metabolic abnormality linked to the development of type 2 diabetes mellitus and cardiovascular disease (CVD). Insulin resistance generally precedes the development of type 2 diabetes. Currently, an estimated 10 million US adults have diabetes and another 25 million have impaired glucose tolerance (IGT), an intermediate step between insulin resistance and diabetes. The pathophysiologic mechanisms known to increase CVD risk in individuals with insulin resistance include formation of advanced glycation end products, hypertension, proinflammatory and prothrombotic states, and dyslipidemia (i.e., low levels of high-density lipoprotein cholesterol, increased levels of triglycerides, small, dense low-density lipoprotein cholesterol particles, apoplipoprotein B, and inflammation). The increased flux of free fatty acids from adipose tissue to the liver promotes dyslipidemia. Insulin resistance and impaired glucose tolerance are associated with increased CVD risk. Individuals with coexisting metabolic syndrome and diabetes have the highest prevalence rates of CVD. The Nurses’ Health Study showed that CVD risk was elevated even before the development of diabetes compared with women who never developed diabetes. Lifestyle modification is recommended as the first-line treatment for obesity and its metabolic sequelae. Pharmacotherapy may be useful in patients for whom nonpharmacologic approaches alone are ineffective or insufficient. Primary care physicians play a critical role in the early identification and treatment of patients at increased risk for the development of type 2 diabetes and CVD because of their obesity and associated complications.

Appetite regulation: from the gut to the hypothalamus.

these proportions had increased to 26% and 22%, respectively, with 55% of women and 66% of men being overweight (BMI > 25 kg/m 2 ; Health Survey for England, 2001), reflecting a worldwide trend which is most marked in, but not restricted to, the developed world. Most of us in affluent countries live in a privileged land of plenty where high calorie foods are easily available and in which we have a limited need for exercise. The rising prevalence of obesity in children is of particular concern (Chinn & Rona, 2001).