AHA Scientific Statement
Clinical Implications of Obesity With Specific Focus on
A Statement for Professionals From the American Heart Association
Council on Nutrition, Physical Activity, and Metabolism
Endorsed by the American College of Cardiology Foundation Samuel Klein, MD; Lora E. Burke, RN, MPH, PhD; George A. Bray, MD; Steven Blair, PED; David B. Allison, PhD; Xavier Pi-Sunyer, MD; Yuling Hong, MD, PhD; Robert H. Eckel, MD Abstract—Obesity adversely affects cardiac function, increases the risk factors for coronary heart disease, and is an
independent risk factor for cardiovascular disease. The risk of developing coronary heart disease is directly related to
the concomitant burden of obesity-related risk factors. Modest weight loss can improve diastolic function and affect the
entire cluster of coronary heart disease risk factors simultaneously. This statement from the American Heart Association
Council on Nutrition, Physical Activity, and Metabolism reviews the relationship between obesity and the cardiovas-
cular system, evaluates the effect of weight loss on coronary heart disease risk factors and coronary heart disease, and
provides practical weight management treatment guidelines for cardiovascular healthcare professionals. The data
demonstrate that weight loss and physical activity can prevent and treat obesity-related coronary heart disease risk
factors and should be considered a primary therapy for obese patients with cardiovascular disease. (Circulation. 2004;

Key Words: AHA Scientific Statements 䡲 obesity 䡲 cardiovascular diseases 䡲 exercise 䡲 diet
Obesity is an important risk factor for coronary heart although the number of fat cells may also be increased, disease (CHD), ventricular dysfunction, congestive particularly in people with childhood-onset obesity.4 In addi- heart failure, stroke, and cardiac arrhythmias. Weight loss in tion, the specific distribution of excess fat can influence the obese patients can improve or prevent many of the obesity- relationship between obesity and cardiac disease. Excess related risk factors for CHD (ie, insulin resistance and type 2 abdominal adipose tissue, particularly visceral fat, and excess diabetes mellitus, dyslipidemia, hypertension, and inflamma- triglyceride content in liver, skeletal muscle, and heart tissues tion)1,2 and can improve diastolic function.3 Therefore, it is are associated with hepatic and skeletal muscle insulin important for cardiovascular healthcare professionals to un- resistance, impaired ventricular function, and increased derstand the clinical effects of weight loss and be able to implement appropriate weight-management strategies in Although an energy deficit of ⬇3500 kcal is needed to obese patients. The purpose of this statement is to review the oxidize 1 lb of adipose tissue, a 3500-kcal energy deficit will physiological and cardiovascular effects of weight loss and cause a ⬎1-lb loss in body weight because of the oxidation of provide clinicians with appropriate treatment guidelines for lean tissue and associated water losses. Approximately 75% weight management in patients with obesity and cardiovas- of weight lost by dieting is composed of fat and 25% is cular disease.
fat-free mass (FFM).10 The addition of exercise training to adiet program can decrease the percentage of weight lost as Clinical Effects of Weight Loss
FFM by half.10,11 Most, if not all, of the loss of fat results from a decrease in the size (triglyceride content) of existing The increase in body fat mass in most obese persons fat cells,12 not a decrease in the number of fat cells.13 The represents primarily an increase in the size of fat cells, distribution of fat loss is heterogeneous, with greater relative The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are requiredto complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on August 18, 2004. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX75231-4596. Ask for reprint No. 71-0303. To purchase additional reprints: up to 999 copies, call 800-611-6083 (US only) or fax 413-665-2671; 1000or more copies, call 410-528-4121, fax 410-528-4264, or e-mail [email protected]. To make photocopies for personal or educational use, call theCopyright Clearance Center, 978-750-8400.
2004 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
Klein et al
Clinical Implications of Obesity
losses of intraabdominal fat than total body fat mass, partic- improvements in serum triglyceride and LDL-C usually occur ularly in men and women with increased initial intraabdomi- within the first 2 months of weight loss.31 The beneficial nal fat mass.14 In addition, diet-induced weight loss decreases effects on serum lipids are related to the percentage of weight intramyocellular15 and intrahepatic16 lipids.
lost, and regaining the lost weight leads to a relapse in serumconcentrations. A sustained weight loss of ⱖ5% is needed to maintain a decrease in serum triglyceride concentrations, Intentional weight loss can improve or prevent many of the whereas serum total and LDL-C revert toward baseline if a obesity-related risk factors for CHD (ie, insulin resistance and ⱖ10% diet-induced weight loss is not maintained.31,32 In type 2 diabetes mellitus, dyslipidemia, hypertension, and contrast, data from the SOS study showed that an average inflammation). Moreover, these metabolic benefits are often weight loss of 33% at 2 years after bariatric surgery decreased found after only modest weight loss (⬇5% of initial weight) serum triglyceride concentrations and increased serum and continue to improve in a monotonic fashion with increas- HDL-C concentrations, but it did not affect serum total ing weight loss.17 The metabolic syndrome represents a constellation of physi- Weight loss decreases both systolic and diastolic blood cal and metabolic abnormalities that are risk factors for pressure in a dose-dependent fashion; therefore, greater cardiovascular disease. The characteristics of this syndrome, weight loss is generally associated with greater improvement as defined by the National Cholesterol Education Program in blood pressure.33,34 Weight regain results in a steady (NCEP) Expert Panel on Detection, Evaluation, and Treat- increase in blood pressure toward baseline. The results of ment of High Blood Cholesterol in Adults (Adult Treatment retrospective analyses of large surgical group experiences Panel III [ATP III]), include large waist circumference, showed that marked weight loss induced by gastric surgery insulin-resistant glucose metabolism (impaired fasting glu- improved or completely resolved hypertension in ⬇67% of cose, impaired glucose tolerance, and type 2 diabetes melli- patients.35,36 In contrast, data from the SOS study revealed tus), dyslipidemia (high triglyceride and low serum HDL-C that on average blood pressure began to progressively in- [cholesterol] concentrations), and increased blood pressure.18 crease 2 years after surgery.27 Most subjects enrolled in the Patients who have the metabolic syndrome have a 1.5- to SOS study underwent vertical banded gastroplasty or gastric 3-fold increase in the risk of CHD and stroke.19–21 Weight banding procedures and lost less weight than those who loss can improve all features of the metabolic syndrome.17 underwent gastric bypass. Subjects who had gastric bypass Insulin Resistance and Type 2 Diabetes Mellitus
surgery maintained a decrease in both systolic and diastolic Insulin sensitivity, with regard to glucose metabolism, im- blood pressure for 5 years after surgery.37 proves rapidly after beginning an energy-deficit diet before Diet-induced weight loss can prevent the development of much weight loss occurs and continues to improve with hypertension in persons who are obese. The results from large continued weight loss.22 In patients with obesity and type 2 epidemiological studies and intervention trials suggest that diabetes mellitus, a 5% weight loss at the end of 1 year of the risk of developing hypertension in normotensive women dietary therapy can decrease fasting blood glucose, insulin, is inversely correlated with changes in body weight.33,38 Data from the SOS study showed, however, that the beneficial 1c concentrations, and the dose of oral hypo- glycemic therapy,23 whereas an average weight loss of ⬇30% effect of gastric surgery-induced weight loss in preventing in extremely obese patients with diabetes after gastric bypass new cases of hypertension disappeared 3 years after surgery, surgery resulted in normalization of blood glucose and despite persistent weight loss.27 glycosylated hemoglobin concentrations in 83% of patients.24 Weight loss can also prevent the development of new Obesity is associated with altered pulmonary function. A diabetes in high-risk persons who are overweight or obese.25–28 marked excess in abdominal fat mass can mechanically Lifestyle dietary and activity modifications, which resulted in interfere with lung function because of the increased weight modest (⬇5%) weight loss, decreased the 4- to 6-year on the chest wall and thoracic cage. In addition, obesity is cumulative incidence of diabetes by ⬎50% in men and associated with serious pulmonary diseases, obstructive sleep women who were overweight or obese and had impaired apnea (OSA), and obesity hypoventilation syndrome (OHS).
glucose tolerance.25,26 The Swedish Obese Subjects (SOS) OSA is characterized by multiple episodes of apnea and Study demonstrated that greater weight losses (⬇16% of hypopnea during sleep caused by partial or complete upper body weight) induced by gastric surgery in patients who are airway obstruction. The interruption in nighttime sleep and extremely obese (initial body mass index [BMI; weight in hypoxemia causes daytime sleepiness and cardiopulmonary kilograms divided by height in square meters] of 41 kg/m2) dysfunction. Episodes of oxygen desaturation during apnea were associated with a 5-fold decrease in the cumulative and hypopnea cause transient increases in pulmonary artery incidence of diabetes for 8 years.27 and pulmonary wedge pressures, and myocardial perfusion defects.39 Over time, electrocardiographic abnormalities and Weight loss decreases serum LDL-C and triglyceride concen- cardiac rhythm alterations, permanent pulmonary hyperten- trations, whereas increases in serum HDL-C typically are sion, right ventricle hypertrophy, and bilateral leg edema can seen when weight loss is sustained.1,29,30 The greatest relative November 2, 2004
OHS is caused by a decreased ventilatory response to CVD risk factors after surgical than medical therapy for hypercapnia, hypoxia, or hypercapnia and hypoxia and inad- obesity, no difference in cardiovascular disease events or equate respiratory muscle strength to meet the increased mortality was found at 10 years.82 ventilatory demand caused by the mechanical effects of Data from large population studies have revealed that obesity. Patients with OHS have shallow and inefficient obesity is associated with increased CVD mortality.83–87 breathing, and a pCO ⬎ 50 mm Hg. Patients may become Moreover, CVD death rates are directly related to BMI in more symptomatic when lying down because abdominal both men and women. The risk of CVD mortality in obese pressure pushes up the diaphragm, which increases intratho- persons who have a BMI ⱖ35 kg/m2 was 2 to 3 times the risk racic pressure and reduces respiratory capacity. Pickwickian among lean persons (BMI 18.5 to 24.9 kg/m2),88 and a 30% syndrome is a severe form of OHS and is associated with higher CHD mortality rate occurs for every 5-unit increment extreme obesity, irregular breathing, cyanosis, somnolence, of BMI.89 In addition, overweight in adolescence is associ- and right ventricular dysfunction.
ated with a 130% increased risk of CHD mortality inadulthood.90 In general, data from large epidemiological studies have Obesity is associated with an increase in circulating inflam- shown that weight variability is associated with an increased matory markers, including C-reactive protein (CRP)43–45 andcytokines (ie, interleukin-6 [IL-6], IL-18, and P-selec- rate of CVD mortality.91 The interpretation of the results from these studies is complicated because many studies assessed 46 – 49 Adipose tissue itself is a likely source of these excess cytokines,46,50 and IL-6 stimulates the production of weight variability rather than weight loss, included large CRP by the liver.51 The increase in inflammatory markers is numbers of lean and mildly overweight subjects, and included associated with insulin resistance52–56 and is an important subjects who experienced "unintentional" weight loss, which predictor of atherosclerotic events.57–61 may have been caused by diseases that influence mortality.
Data from studies that have ranged in duration from 3 Therefore, the available data are not adequate to reliably months to 2 years have revealed that weight reduction determine whether intentional weight loss affects CVD mor- decreases plasma CRP concentration.49,52,62–67 The decrease tality, and carefully designed RCTs are needed to address this in CRP is directly related to the amount of weight loss, fat mass, and change in waist circumference. In one study, onlysubjects who were insulin resistant experienced a weight Cardiovascular Structure and Function
loss–induced decrease in CRP, an effect that paralleled Obesity, particularly severe obesity, is associated with abnor- changes in insulin sensitivity.52 Plasma CRP concentrations malities in cardiac structure and function.8,92 The severity of did not decrease and insulin sensitivity did not increase in these defects is associated with both the degree and duration subjects who were insulin sensitive before weight reduction.
of obesity.93 Obesity is associated with an increase in total Decreases in plasma IL-6,48,49,65,67–69 IL-18,49,67 P-selectin,48 blood volume and cardiac output and a decrease in peripheral and tumor necrosis factor-␣48 concentrations have also been vascular resistance.8,94 In this setting, ventricular filling reported66,68,69 after weight loss in subjects who are obese.
pressures are elevated,95 which eventually results in increasedwall stress, diastolic dysfunction, and left ventricular hyper- Autonomic Nervous System Dysfunction
trophy.93,96,98 Abnormalities of the right heart can also occur Overweight and obesity are associated with cardiac auto- and may represent a combination of left heart disease, nomic neuropathy. For example, a 10% increase in body recurrent pulmonary thromboemboli, and OSA or hypoven- weight is associated with a decline in parasympathetic tone tilation or both.99 Finally, lipomatous deposition in the and an increase in heart rate.70 Alterations in autonomic interatrial septum has also been described100; however, this nervous system function might be an important cause of anatomic alteration is unlikely to contribute to cardiac cardiovascular disease events and mortality, as suggested by the relationship between heart rate and cardiovascular disease Weight loss, particularly in persons who are severely mortality.71,72 Marked weight loss induced by bariatric sur- obese, can improve cardiac structure and function.3,101 Im- gery increases vagal activity.73 In addition, weight loss provements in fractional shortening are associated with de- achieved by dieting also increases cardiac parasympathetic creases in hypertension and left ventricular internal dimen- activity,74–77 but this increase is not maintained in the absence sion with reduced atrial and left ventricular free and septal of sustained weight loss.77 wall thickness. Moreover, improvements in left ventricular diastolic filling and ejection fraction also occur.102 Improve- Although weight loss modifies many cardiovascular disease ments in left ventricular mass occur in both normotensive and (CVD) risk factors, it is not known whether weight reduction hypertensive patients and are independent of the reduction in decreases CVD events or CVD mortality in obese per- blood pressure.103,104 In addition, adding exercise to a low- sons.78–80 This important question has not yet been answered calorie diet (LCD) may produce greater benefits in cardiac because it is difficult to achieve prolonged periods of sus- structure105,106; however, these benefits are not consistent tained weight reduction (eg, ⬎5 years) with nonsurgical across all studies.107,108 For example, substantial weight loss therapy81 and to perform prospective randomized controlled (⬇15% of baseline)108 and modest weight loss plus physical trials (RCTs) involving bariatric surgery. Data from the SOS training109 did not have beneficial cardiac effects in obese study showed that despite a greater reduction in weight and adolescents. At present, the potential benefits of weight loss Klein et al
Clinical Implications of Obesity
on cardiac function are not completely clear and require Suggested Energy and Macronutrient Composition of
further study.
Initial Reduced-Calorie Diet
Clinical Efficacy of Obesity Therapies
The goals of obesity therapy include decreasing body fat to improve appearance, physical function, quality of life, and medical health. Although surgical removal of large amountsof subcutaneous adipose tissue (ⱕ20% of total body fat mass) can improve a person's appearance, ability to ambulate, and quality of life, it does not improve the metabolic CHD risk factors associated with obesity110; it seems that fat lossinduced by negative energy balance is necessary to achieve support the notion that decreasing fat intake, even while metabolic benefits. Current therapies available for weight allowing ad libitum intake of carbohydrates and proteins, management that cause weight loss by inducing a negative causes a spontaneous decrease in total energy intake and energy balance include dietary intervention, physical activity, weight loss.115 In addition, a survey of obese persons who pharmacotherapy, and surgery. Behavior modification to were successful at maintaining long-term weight loss found enhance dietary and activity compliance is an important that they consumed ⬍25% of calories from fats.116 However, component of all of these treatments.
a recent systematic review of randomized controlled studiesthat were specifically conducted to evaluate dietary therapy for obesity found that weight loss induced by low-fat diets Many different diets have been proposed for the treatment of and other weight-reducing diets were similar.117 The compos- obesity. These dietary approaches vary in their total energy ite of these data suggests that low-fat diets can enhance prescription, macronutrient (fat, carbohydrate, and protein) weight loss and may be particularly useful in selected content, energy density, glycemic index, and portion control.
The energy content of a diet is the primary determinant of persons, but they are not necessarily more effective than weight loss. Very-low-calorie diets (VLCDs) provide ⬍800 kcal/d, LCDs usually contain 800 to 1500 kcal/d, and a The use of low-carbohydrate diets has become increasingly balanced-deficit diet usually provides ⱖ1500 kcal/d. An LCD popular. Several RCTs compared the effect of low- usually causes an ⬇8% loss of body weight at ⬇6 months of carbohydrate, high-protein, high-fat diets (eg, the Atkins diet) treatment. The results from clinical trials may not reflect the with a conventional low-fat diet (⬇30% energy from fats) in experience in clinical practice because these trials involved adults118–123 or a very-low-fat diet (⬇12% energy from fats) subjects who volunteered for a weight loss study and often in adolescents.124 In all studies, weight loss at 3 and 6 months included formal behavior modification as part of the study in subjects randomized to the low-carbohydrate diet was ⬇2 protocol. The use of a VLCD usually produces a weight loss times as great (⬇4- to 5-kg greater weight loss) as those of ⬇15% to 20% within 4 months111–113; however, VLCDs randomized to the low-fat group. In 2 studies that observed are associated with poorer weight loss maintenance and a patients for 1 year, weight loss at 1 year was not significantly greater weight regain than are LCDs, so weight loss at 1 year different between groups, however.121,122 In general, these after treatment with a VLCD does not differ from treatment studies also found the low-carbohydrate diet was more with an LCD.113 In addition, treatment with a VLCD may be beneficial in serum triglyceride and HDL-C concentrations as particularly problematic for patients with CHD because of the compared with the low-fat diet, but the low-fat diet was more risk of diet-induced hypokalemia, dehydration, and beneficial in serum LDL-C concentration. Although these changes in triglycerides and HDL-C after weight reduction on The macronutrient composition of a diet does not affect the low-carbohydrate diets appear favorable, it is not known rate of weight loss unless macronutrient manipulation influ- whether these alterations are associated with long-term ben- ences total energy intake or expenditure. The Expert Panel on eficial effects on CHD.125 the Identification, Evaluation, and Treatment of Overweight The type of carbohydrate consumed also may be involved and Obesity in Adults convened by the National Institutes of in regulating energy intake, and a low glycemic index diet has Health/National Heart, Lung, and Blood Institute recom- been proposed as a treatment for obesity. The glycemic index mended a 500- to 1000-kcal/d deficit diet for obese persons, refers to the increase in blood glucose that occurs after which will initially result in a weekly weight loss of 1 to 2 lb consuming a fixed amount (usually 50 g) of available (0.45 to 0.9 kg). It is often difficult, however, to accurately carbohydrate from a test food relative to the increase in blood determine a patient's daily energy requirements. Therefore, glucose that occurs after consuming the same amount of calorie-intake guidelines for a weight-loss diet have been available carbohydrate from either glucose or white suggested based on a patient's initial body weight (Table bread.126,127 Most refined grain products and potatoes have a 1).114 The calorie content of any prescribed diet must be high glycemic index, whereas most fruits, legumes, and adjusted regularly, based on the patient's weight-loss re- nonstarchy vegetables have a low glycemic index. The sponse and treatment goals.
glycemic response to a specific food that is ingested as part of A low-fat diet is considered the standard approach for the a meal can be altered by many factors, such as the method of treatment of obesity.1 Data from diet intervention studies preparation and the effect of concomitantly ingested foods on November 2, 2004
intestinal motility. Data from a small (n⫽14) randomized Suggested Dietary Nutrient Composition for
controlled 1-year trial conducted in overweight adolescents Patients Who Are Overweight or Obese
revealed that a reduced glycemic index diet resulted in a Recommended Intake greater decrease in body weight and BMI than did a reduced- ⬍7% of total calories fat diet.128 The writing group is unaware of any RCTsevaluating the effect of a low glycemic index diet on body Monounsaturated fat ⱕ20% of total calories weight in adults.
Polyunsaturated fat ⱕ10% of total calories The use of low-energy-density foods may be another 25% to 35% or less of total calories effective approach for treating obesity. The energy density of 50% to 60% or more of total calories (complex a diet is defined as the calories present in a given weight of carbohydrates from a variety of vegetables, fruits, food. A food's energy density is directly correlated with its fat content and inversely correlated with its water content.
Energy intake during a meal is partially regulated by the ⬇15% of total calories weight of ingested food and is inversely correlated with energy density.129 Moreover, the results of a 6-month RCTdemonstrated that providing subjects with ad libitum low-fat preferably all days of the week.136–138 The health benefits of and low-energy-density foods causes modest (1% to 2%) 30 minutes of daily moderate-intensity physical activity apply to all persons. Data from several studies show that persons Portion control is an important aspect of reducing energy who are overweight or obese and physically active (ie, intake. During ad libitum feeding, a direct relationship is participate in ⱖ30 minutes of moderate-intensity physical found between portion size served and intake; therefore, activity most days of the week) or who have moderate to high increasing the size of the portion served increases the amount levels of cardiorespiratory fitness (ie, in the upper four fifths of food consumed.131 of the age and sex fitness distributions) have much lower Providing prepackaged prepared meals, either as frozen death rates from cardiovascular disease and all-cause mortal- entrees of mixed foods or liquid-formula meal replacements ity than people who are sedentary and unfit.87,139–143 There- improves portion control and can enhance weight loss. Datafrom RCTs have shown that obese persons who were given fore, regular physical activity may improve survival in prepackaged prepared meals or liquid-formula meal replace- persons who are overweight or obese, independent of weight ments lost several kilograms more weight than did those who were randomized to a standard diet.132–134 Educating patients Weight loss results from a negative energy balance, which about food labels, recipe modification, restaurant ordering, can be achieved by decreasing energy intake, increasing social eating, and healthy cooking methods are also important energy expenditure, or both. It is usually much easier to to help patients understand portion size and energy intake induce a daily energy deficit by restricting energy intake than during meals and snacks.
by increasing energy expenditure. The calories consumed In summary, the data from RCTs demonstrate that different during physical activity can be estimated as a function of a dietary interventions can cause short-term weight loss. At the metabolic equivalent task (MET) score. One MET is the present time, we suggest that patients who are overweight or energy consumed during resting conditions, such as television obese and trying to lose weight consume a diet that induces an viewing, and is equal to ⬇1 kcal/kg of body weight per hour.
energy deficit of 500 to 1000 kcal/d and has a macronutrient Other activities such as carrying packages, doing housework composition that is known to reduce the risk of CVD. This or gardening (2 to 5 METs), walking at a pace of 3 to 4 mph diet involves (1) consuming a variety of fruits, vegetables, (3 to 4 METs), and jogging (8 to 10 METs) consume greater grains, low-fat or nonfat dairy products, fish, legumes, amounts of energy. A person weighing 90 kg would need to poultry, and lean meats; (2) limiting intake of foods that are walk briskly for 4 to 5 h/d to increase his or her energy high in saturated fat, trans-fatty acids, and cholesterol; and expenditure above resting metabolic rate by an amount that is (3) following the current dietary guidelines of the American equivalent to reducing energy intake by 750 to 1000 kcal/d.
Heart Association135 and the NCEP ATP III18 (Table 2).
Therefore, it is difficult to lose a substantial amount of weight These recommendations may require modification, based on through physical activity. A review of 19 studies with the results of ongoing and future dietary therapy studies. The randomized designs showed that exercise plus diet caused a key to successful weight management is to provide patients 0.1-kg/wk greater weight loss than did diet alone.144 Weight with a dietary regimen that results in long-term compliance.
loss induced by combining physical activity with diet de- The available data suggest that it is unlikely that one creases the loss of FFM that occurs when weight loss is approach is appropriate for all patients.
induced by diet alone.145 Data from observational studies strongly support the notion that physical activity is critical for preventing weight re- Regular physical activity has important health benefits. A gain.145,146 Moreover, the available evidence suggests that a consensus public health recommendation for physical activity high volume of physical activity, 80 to 90 minutes of developed in the mid-1990s proposed that sedentary adults moderate-intensity activity such as walking or 35 minutes of should accumulate ⱖ30 minutes of at least moderate- vigorous activity such as jogging, is necessary to maintain intensity physical activity (eg, brisk walking) on most but weight loss.145 The interpretation of the results from these Klein et al
Clinical Implications of Obesity
studies is complicated because subjects who achieved suc- Behavioral Strategies to Improve Weight Management
cessful long-term weight loss had chosen to be physically active and had not been randomized a priori to a high-volumephysical activity program. Data from a recent prospective Record "what, where, and when" of eating andphysical activity to increase patients' RCT revealed that high-volume physical activity did not awareness of their own behavior.
completely prevent weight regain.147 Nonetheless, weight Set specific short-term targets in eating and regain after 6 months was smaller and total weight loss was exercise habits to achieve incremental greater at 12 and 18 months in obese subjects who were randomized to dietary and behavior therapy plus high-volume Identify triggers associated with poor eating physical activity (2500 kcal of energy expenditure per week) and physical activity behaviors, and design than they were in persons randomized to dietary and behavior strategies to break link.
therapy plus conventional physical activity (1000 kcal of Cognitive restructuring Change perceptions, thoughts, or beliefs energy expenditure per week). Although it is in general undermining weight control efforts, and help difficult to achieve long-term adherence to an exercise patients develop realistic expectations about program, several approaches have been used to enhance weight loss.
adoption and maintenance of physical activity. Behavior- Analyze situations preventing maintenance of a intervention strategies originally developed for smoking ces- healthier lifestyle and identify possible solutions sation or dietary programs have been used to increase to problems; maintain philosophy that planning,not willpower, is key to weight management.
physical activity. One study showed comparable improve-ments over 24 months in activity, fitness, and CHD risk Relapse prevention Develop skills based on premise that lapses inweight control behavior can be anticipated in factors for participants who were randomly assigned to a certain situations (eg, travel, celebrations, bad traditionally structured gymnasium-based program or to a behaviorally based intervention.148 Increased contact by mail Stress management Decrease psychological stress to prevent or telephone also helps maintain long-term adherence to exercise.149 Total exercise time during the course of a study is Contingency management Use rewards (tangible or verbal) to increase greater when daily exercise is divided into multiple short performance of specific behaviors or when bouts (eg, 10-minute bouts 3 to 4 times per day) than one long specified goals reached.
bout (eg, 30- to 40-minute bout once per day)150; ie, multiple Use assistance from family members and short bouts of exercise result in greater adherence to an friends in modifying lifestyle behaviors.
exercise program. In addition, many patients may be more Maintain visits, telephone calls, or Internet compliant with an exercise program conducted at home than communication with physician and office staff at a health club because fewer barriers are found with or other healthcare professionals to promote home-based exercise, including costs and travel time. Devel- adherence with recommended lifestyle oping a home-based walking program and using home exer- cise equipment such as a treadmill has been shown toimprove exercise adherence and long-term weight loss.151,152 Finally, exercise does not need to be a structured activity.
Behavior therapy focuses on analyzing and modifying eating Altering daily lifestyle activities (eg, walking instead of and activity behaviors that increase body weight and provides riding, using stairs instead of escalators/elevators) may make techniques to help patients change their lifestyle habits and it easier to increase overall physical activity than would overcome barriers to compliance. A summary of behavioral participation in programmed exercise. In one study, weight strategies for treating obesity is shown in Table 3. The most loss was similar after dietary therapy plus either lifestyle important principles of behavioral treatment are that it (1) is activity or programmed exercise, but a trend toward better goal-oriented and specifies goals that can be easily attained maintenance of weight loss 1 year after treatment was and measured, (2) is process-oriented and helps patients observed in individuals randomized to lifestyle activity than develop realistic goals and a reasonable plan for reaching to programmed exercise.153 Although these strategies are a those goals, and (3) involves making small rather than large welcome improvement, all studies still report a decline in changes so that incremental steps are taken to achieve larger exercise adherence over time.148,149,151,154 and more distant goals.155,156 In summary, physical activity is not an effective approach for achieving initial weight loss, but it does have beneficial Self-monitoring, the systematic observation and recording effects on fitness and obesity-related complications such as of target behaviors, is the cornerstone of behavioral treat- CHD and diabetes. In addition, a high level of regular ment.156 Self-monitoring tools include (1) food diaries in physical activity is important for preventing and attenuating which to record food intake, including types, amounts, energy weight regain after diet-induced weight loss. Most data contents, and times, places, and feelings associated with suggest that it is the total volume of physical activity that is eating (usually in paper-and-pencil format but also available important to weight management and that it does not matter on the Internet or in commercially available programs for use whether the activity is of moderate or vigorous intensity, a on a personal digital assistant), (2) physical activity logs in lifestyle or structured program, or taken in a single bout each which to record the frequency, duration, and intensity of day or in several intermittent bouts.
exercise or step counters on which to monitor the daily steps November 2, 2004
taken, and (3) weight scales on which to measure changes in Drugs Approved by FDA for Treating Obesity
body weight. Self-monitoring increases patients' awareness of their behaviors, generates records that can be reviewed by healthcare professionals, and provides targets for In clinical practice, formal behavior therapy can be pro- vided through group sessions or individual meetings with a healthcare professional who is skilled in the delivery of behavioral techniques used to modify lifestyle habits.155,157 If possible, contact should be regular, preferably once every 1 to Phendimetrazine tartrate 2 weeks, during the initial 6-month phase of a treatment DEA indicates Drug Enforcement Agency.
program.155 Comprehensive group behavior therapy, in con-junction with diet and physical activity, usually results in an considerable economic incentive exists for the obese ⬇9% body weight loss within 26 weeks of treatment (⬇0.5 patient to discontinue taking these medications.
kg/week).157 Patients usually regain ⬇33% of their lost Medications for the treatment of obesity available in the weight in the year after ending behavior therapy, but most United States are listed in Table 4. Effective therapy for still maintain a weight loss of ⱖ5% at the end of 1 year.
obesity usually requires chronic intervention; however, only 2 Providing ongoing contact by scheduled visits, telephone drugs, sibutramine and orlistat, are approved for long-term calls, food evaluation and exercise diaries, and Internet communication can enhance long-term adherence and helpsprevent weight regain.158,159 In addition, Internet-based treat- ment programs for weight loss160,161 and structured commer- cial programs such as Weight Watchers162 can augment the Sibutramine is a ␤-phenethylamine derivative that blocks professional guidance provided by the physician.
the reuptake of norepinephrine, sibutramine, and, to a lesserdegree, dopamine. Sibutramine decreases food intake by producing early satiety during feeding and by delaying Pharmacotherapy can help selected patients lose weight. The initiation of the next meal. Although sibutramine has no approved indications for drug therapy for obesity are a BMI potential for abuse, it is classified as a Schedule IV drug.
ⱖ30 kg/m2 or a BMI between 27 and 29.9 kg/m2 in conjunc- Sibutramine is available in 5-, 10-, and 15-mg doses; 10 mg/d tion with an obesity-related medical complication in patients as a single daily dose is the recommended starting level, with with no contraindications for therapy. Effective pharmaco- titration up or down based on response. Doses ⬎15 mg/d arenot recommended.
therapy for obesity is likely to require long-term, if notlifelong, treatment because patients who respond to drug Clinical Efficacy therapy usually regain weight when the therapy is stopped.
In a 1-year RCT, subjects treated with sibutramine lost 7% The expected length of drug treatment of obese patients who of their initial body weight and those treated with placebo lost respond to therapy makes it important to carefully consider 2%. Of the subjects treated with sibutramine or placebo, 57% the long-term risks of being obese, the beneficial effects of and 20%, respectively, lost ⱖ5% of their initial body weight;34% and 7%, respectively, lost ⱖ10% of their initial body pharmacotherapy on body weight and obesity-associated weight.167 Weight loss with intermittent sibutramine therapy diseases, and the side effects and costs of treatment before (15 mg/d given during weeks 1 through 12, 19 through 30, beginning therapy. In addition, pharmacotherapy alone is not and 37 through 48, and placebo given during the two 6-week as effective as pharmacotherapy given in conjunction with a periods when sibutramine was withdrawn) was equivalent to comprehensive weight-management program.163 Therefore, weight loss with continuous sibutramine therapy (15 mg/ patients given drug treatment without the other standard d).168 Sibutramine therapy also has been shown to maintain approaches to weight management, including behavior mod- weight loss for 12 to 18 months in subjects who initially lost ification, diet education, and activity counseling, are exposed weight by eating a VLCD163 or who successfully lost weight to all of the risks of drug treatment without all of the medical after 6 months of sibutramine treatment.170 The use of sibutramine in obese patients with either medication-controlled hypertension171 or type 2 diabetes mellitus172 Drug therapy adds a level of complexity to the treatment of causes greater weight loss than with placebo therapy, but the obesity. The patient with medication prescribed for obesity overall weight loss is less than that observed in studies may have comorbidities that already require pharmacother- conducted in subjects who do not have comorbid disease.
apy, thereby increasing the likelihood of nonadherence.164 Weight loss with sibutramine therapy is more effective Strategies to enhance medication compliance include regu- when combined with behavior and dietary therapies. In a larly assessing adherence and response to therapy, counseling 1-year RCT, weight loss with sibutramine therapy alone was about and reinforcing the importance of adherence, simplify- ⬇5 kg, with sibutramine therapy plus behavior modification ing the treatment regimen, assisting the patient in reducing was ⬇10 kg, and with sibutramine therapy plus behavior barriers to adherence, providing reminders and cues to modification and a structured meal plan was ⬇15 kg.173 facilitate improved adherence, and enlisting support when Side Effects and Safety needed.159,164 –166 In addition, weight loss drugs usually are The most common side effects of sibutramine are dry not covered by health insurance or health care plans, so a mouth, constipation, and insomnia. Sibutramine increases Klein et al
Clinical Implications of Obesity
heart rate (a dose of 10 to 15 mg/d causes an increase in heart Side Effects and Safety rate of 4 to 6 bpm) usually in the first few weeks of treatment About 70% to 80% of subjects treated with orlistat and lasts as long as the drug is taken. Sibutramine also causes experienced ⱖ1 gastrointestinal event as compared with a dose-related increase in blood pressure (a dose of 10 to 15 ⬇50% to 60% of those treated with placebo. Gastrointes- mg/d causes an average increase in systolic and diastolic tinal events usually occurred early (within the first 4 blood pressure of 2 to 4 mm Hg) and can prevent weight weeks), were of mild or moderate intensity, were usually loss–induced decrease in blood pressure.155 Therefore, careful limited to 1 or 2 episodes, and resolved despite continued monitoring is needed when combining sibutramine with other orlistat treatment. Approximately 4% of subjects treated drugs that can increase blood pressure. Sibutramine should with orlistat and 1% of subjects treated with placebo not be used in patients who have uncontrolled hypertension, withdrew from the studies because of gastrointestinal a history of coronary artery disease, congestive heart failure, complaints. During treatment, small decreases in plasma cardiac arrhythmias, or stroke, or who are being treated with fat-soluble vitamins, particularly vitamins A, D, and E, can monoamine oxidase inhibitors or selective serotonin reuptake occur, although plasma concentrations almost always re- main within the reference range. A few patients, however,may experience decreases in plasma vitamin concentra- CVD Risk Factors tions to below the reference range. Because it is impossible The composite data from RCTs demonstrate that sibutra- to determine a priori which patients will need vitamin mine causes improvements in serum triglyceride, total cho- supplements, it is recommended that all patients who are lesterol, LDL-C, and HDL-C concentrations that are directly treated with orlistat be given a daily multivitamin supple- related to the magnitude of the weight loss. However, ment that is taken at a time when orlistat is not being sibutramine therapy decreases or eliminates weight loss– induced benefits on blood pressure.
Orlistat can have medically significant effects on the absorption of lipophilic medications if both drugs are takensimultaneously. Subtherapeutic plasma cyclosporin levels that occurred in organ transplant recipients after they began Orlistat blocks the digestion and absorption of dietary fat orlistat therapy for obesity have been reported.186–189 There- by binding to intestinal lipases.174 The percentage of fat that fore, orlistat should not be taken for ⱖ2 hours before or after is malabsorbed is related to drug dose in a curvilinear the ingestion of lipophilic drugs, and plasma drug concentra- fashion.175 Near-maximal fat malabsorption occurs at a dose tions should be followed to ensure appropriate dosing. Or- of 120 mg when given with a meal, which causes malabsorp- listat does not affect the absorption of selected drugs with a tion of ⬇30% of fat ingested from a meal that contains ⬇30% narrow therapeutic index (warfarin, digoxin, phenytoin) and of energy as fat. Less than 1% of ingested orlistat is absorbed; selected drugs that are likely to be taken concomitantly with therefore, it has no effect on systemic lipases.176 orlistat (glyburide, oral contraceptives, furosemide, captopril, Clinical Efficacy nifedipine, and atenolol).189 The effects of orlistat on body weight and CHD risk factors CVD Risk Factors have been evaluated in a large number of RCTs. The data Because of its weight loss effects, orlistat therapy from most studies demonstrate that at 1 year, subjects who improves all major cardiovascular disease risk factors such were randomized to orlistat therapy (120 mg tid) lost ⬇8% to as blood pressure and insulin sensitivity. Moreover, data 10% of their initial body weight and those randomized to from several RCTs suggest that orlistat has a beneficial placebo therapy lost ⬇4% to 6%.177–181 Approximately 33% effect on serum cholesterol concentrations that is indepen- more patients treated with orlistat lost ⱖ5% of their body dent of weight loss alone. Subjects given orlistat had a weight than did those treated with placebo; ⬇2 times as many greater reduction in serum LDL-C concentrations than patients treated with orlistat lost ⱖ10% of their body weight those given placebo, even after adjusting for percentage of as did those treated with placebo. Ending orlistat therapy weight loss.178,179 The mechanism responsible for this results in weight regain,177,180 and starting orlistat therapy additional lipid-lowering effect may be related to the effect after successful diet-induced weight loss helps maintain body of orlistat in blocking both dietary cholesterol and triglyc- weight.182 In subjects with obesity and type 2 diabetes eride absorption.190 In contrast, orlistat is not as effective mellitus who are treated with sulfonylureas,183 metformin,184 in lowering serum triglyceride concentrations, presumably or insulin,185 the percentage who achieve a ⱖ5% or ⱖ10% because it increases the proportion of absorbed energy reduction in body weight is 2 to 3 times higher in those derived from carbohydrate, which tends to increase serum receiving orlistat plus dietary therapy than it is in those receiving dietary therapy alone. The overall weight loss effectof orlistat therapy in patients with diabetes is less than that reported in previous studies of obese patients who did not Phentermine is a ␤-phenethylamine derivative that stimu- have diabetes, however.
lates the release of norepinephrine and dopamine from Recently, the results of a 4-year RCT were reported.28 The nerve terminals. Although phentermine is not approved by lowest body weight was achieved during the first year and the Food and Drug Administration (FDA) for long-term was greater in the orlistat-treated group (11% weight loss) use, it is the most commonly prescribed anorexiant medi- than in the placebo-treated group (6% weight loss). Subjects cation in the United States,192 presumably because it is less regained weight during the remainder of the trial; orlistat-treated subjects had lost 6.9% of their initial body weight and expensive than sibutramine. Phentermine was approved by placebo-treated subjects had lost 4.1% at the end of 4 years.
the FDA ⬎30 years ago, when the criteria needed for Orlistat therapy also decreased the cumulative 4-year inci- approval were less rigorous than they are currently. There- dence of type 2 diabetes mellitus by 37%.
fore, fewer studies have evaluated the efficacy and safety November 2, 2004
of phentermine therapy than have evaluated sibutramine Effect of Different Bariatric Surgical Procedures on
and orlistat. Only one long-term (36 weeks) RCT evaluated Long-Term (>2 y) Body Weight
the effect of phentermine therapy on body weight.193 In that study, obese women were randomized to dietary therapy and treatment with daily phentermine, daily phen- termine every other month alternating with daily placebo every other month, or daily placebo. Of the 108 enrolled subjects, approximately two thirds completed the study; among those who completed the study, the groups that Biliopancreatic diversion ⫾ received either continuous or intermittent phentermine therapy lost ⬇13% of their initial weight as compared witha 5% weight loss in the placebo group.
proximal gastric pouch, which empties into a segment of Side Effects and Safety jejunum that is anastomosed to the pouch as a Roux-en-Y The most common side effects of phentermine are dry limb. Gastroplasty involves the formation of a small pouch mouth, insomnia, and constipation. Although all sympatho- along the lesser curvature near the gastroesophageal junc- mimetic agents can increase blood pressure and heart rate, tion, which empties into the rest of the stomach through a these side effects are uncommon when weight loss is 1-cm outlet stoma. Gastric banding involves the placement of a band around the upper stomach. The band circumfer-ence size can be changed by percutaneously inflating or deflating a balloon in the band that is connected to a Several different dietary supplements and herbal preparations subcutaneous port and is commonly adjusted after surgery have been used to treat obesity, including chromium picoli- based on weight loss response and gastrointestinal symp- nate, garcinia cambogia as a source of hydroxycitrate, chi- toms. Biliopancreatic diversion involves the creation of a tosan that is claimed to reduce fat absorption, phenylephrine 200- to 500-mL proximal gastric pouch and transsection of from Citrus aurantium (bitter orange), and ma huang as a the small intestine 250 cm from the ileocecal valve; the distal source of ephedra alkaloids with or without guarana as a end of the small intestine is anastomosed to the gastric pouch source of caffeine. In general, few RCTs have evaluated the and the proximal limb anastomosed to the ileum 50 cm from the clinical efficacy of these agents, and most of the RCTs that ileocecal valve. These anastomoses create a 200-cm "alimentary have been done were of substandard quality194–196; however, tract," a variable length (300 to 500 cm) "biliary tract," and a data from several RCTs demonstrated greater weight loss in 50-cm "common tract" in which digestion and absorption of subjects given herbal products that contain ephedra than in ingested food occur. The biliopancreatic diversion with duode- those given placebo.197,198 Nonetheless, the sale of ephedra in nal switch procedure involves the removal of ⬇60% of the over-the-counter products was recently banned by the FDA greater curvature of the stomach and transection of the proximal because of concerns about serious adverse cardiovascular duodenum. The proximal portion of the duodenum is anasto- mosed end-to-end to the distal small intestine 250 cm proximalto the ileocecal valve. The distal end of the resected proximal intestine, which receives secreted pancreatic enzymes, is anas- Bariatric surgery is the most effective therapy available for tomosed to the ileum 100 cm proximal to the ileocecal valve. All people who are extremely obese. The current indications for bariatric surgical procedures have been performed as open and surgical therapy were established at a consensus conference held at the National Institutes of Health in 1991.199 The panel The approximate weight loss reported after each procedure recommended that bariatric surgery be considered for obese is shown in Table 5.114 It is difficult to determine the relative persons who have a BMI of 35.0 to 39.9 kg/m2 plus ⱖ1 weight loss effectiveness of each procedure because only severe obesity-related medical complication such as hyper- vertical banded gastroplasty and gastric bypass have been tension, type 2 diabetes mellitus, heart failure, or OSA and compared directly in RCTs.200–203 The data from these RCTs persons with a BMI ⱖ40 kg/m2. At present, ⬇109 000 consistently revealed that weight loss was greater with the bariatric surgery procedures are performed each year in the gastric bypass procedure than with vertical banded gastro- United States.
plasty. Fewer studies have evaluated the long-term effects of Five surgical procedures are most commonly used to gastric banding, biliopancreatic diversion, and biliopancreatic treat obesity: (1) gastric bypass (Roux-en-Y anastomosis), diversion with duodenal switch than gastric bypass or gastro- (2) gastroplasty (gastric stapling, vertical banded gastro- plasty because the procedure has been more recently devel- plasty, silastic ring gastroplasty), (3) gastric banding oped or has been performed less often.
(LAP-BAND), (4) biliopancreatic diversion (partial bilio- The perioperative mortality rate within 30 days after pancreatic bypass), and (5) biliopancreatic diversion with open bariatric surgery is ⬇1%23,200,204,205 but can vary duodenal switch (partial biliopancreatic bypass with duo- depending on the experience of the surgeon.206 Approxi- denal switch). Gastric bypass accounts for ⬇70% of the mately 75% of deaths are caused by anastomotic leaks and bariatric operations performed in the United States. This peritonitis and 25% by pulmonary embolism. Laparoscopic procedure involves the construction of a small (⬇20 mL) gastric bypass is associated with fewer wound complica- Klein et al
Clinical Implications of Obesity
Weight Classification by BMI*
and timing of meals and snacks and an attempt to identifypossible triggers that result in excessive energy intake, (3) physical activity and function (daily and exercise activi- ties, physical limitations, effect of obesity on physical lifestyle), (4) obesity-related health risk (age of onset and duration of obesity, family history of obesity and obesity- related medical complications, current obesity-related dis- ease), (5) possible psychiatric illnesses, such as bingeeating disorder and depression, that may require therapy before a weight loss program is initiated, and (6) ability to *Data from Obes Res.1 lose weight (desire to lose weight, weight loss goals and Additional adiposity-related risk factors: waist circumference ⬎40 (in men) expectations, limitations for achieving weight loss, includ- ⬎35 (in women); weight gain of ⱖ5 kg since age 18–20 y.
ing medications and illnesses, lifestyle and work patterns,financial resources, and special needs).
tions, less postoperative pain, less blood loss, and shorterhospital stays and convalescence periods than does the open procedure207; however, late anastomotic strictures The patient's BMI and waist circumference should be occur more frequently after the laparoscopic than after the determined. BMI is generally correlated with percentage of open procedure.
body fat in a curvilinear fashion.208 Some people with an"obese" BMI, who have a normal amount of body fat and a large muscle mass, are not at increased risk for CHD, The goal of weight loss therapy for patients with CVD is to whereas people with a "normal" BMI, who have excessive reduce or eliminate CHD risk factors and improve cardiac body fat and small muscle mass, are at increased risk.
function. Aggressive weight loss therapy could be harmful in Waist circumference, measured halfway between the last selected patients, such as those who have had a recent rib and the iliac crest, correlates with abdominal fat mass.5 myocardial infarction or stroke or who have unstable angina, Table 6 provides a classification of risk based on BMI. A and attempts at weight loss should be delayed until these waist circumference of ⱖ88 cm (35 in) for women and patients are medically stable.
ⱖ102 cm (40 in) for men is associated with an increasedrisk of metabolic diseases and CHD.1 Additional assess- ments should include measuring blood pressure with a The physician's office should be an environment that is large cuff and searching for physical signs of right or left sensitive to the needs of obese patients. The waiting room ventricular dysfunction, congestive heart failure, and pul- should contain chairs without arms, large gowns and large monary disease. An electronic stethoscope can increase a blood pressure cuffs should be available, and a scale that can physician's ability to detect cardiac abnormalities in pa- weigh patients who weigh ⬎300 lb should be available and tients who are extremely obese.
located in a private area. The initial assessment shouldinclude an appropriate history, physical examination, and laboratory tests.
An ECG is needed to check for evidence of CHD and toobtain a baseline tracing for future comparisons. Standard blood tests should be performed to search for CHD risk In addition to a standard medical interview, a patient's factors, including prediabetes (impaired fasting blood history should include an assessment of (1) weight history glucose or impaired glucose tolerance), dyslipidemia (in- (highest and lowest adult body weight, previous weight creased triglycerides, low HDL-C, and increased LDL-C), loss attempts, weight pattern, and potential triggers and and the metabolic syndrome. Additional studies may be social and environmental factors that contributed to weight needed to further evaluate specific clinical suspicions gain), (2) dietary history, including an assessment of types based on the history and physical examination, such as Weight Loss Treatment Guidelines*
BMI Category, kg/m2 Diet, physical activity, behavior therapy, or all 3 With obesity-related disease With obesity-related disease *Data from Obes Res.1†Pharmacotherapy should be considered only in patients who are not able to achieve adequate weight loss by available conventional lifestyle modifications and who have no absolute contraindications for drug therapy.
‡Bariatric surgery should be considered only in patients who are unable to lose weight with available conventional therapy and who have no absolute contraindications for surgery.
November 2, 2004
sleep studies to diagnose OHS or OSA and an exercise tient's priorities, motivation, or confidence in undertaking treadmill test or electron beam computerized tomography change.213 In contrast, obesity therapy should involve scanning or both to evaluate CHD risk. The comparative "patient-centered counseling," which encourages patients value of exercise tolerance testing and electron beam to set goals and express their own ideas for therapy, with computerized tomography in obese subjects has not been input from the healthcare professional. The treatment plan determined. Exercise treadmill testing is not recommended also must take into account the patient's readiness for for patients without cardiac symptoms, and neither exer- therapy and the patient's ability to comply with the cise treadmill testing nor electron beam computerized proposed treatment plan. Realistic goals should be estab- tomography scanning should be performed in patients who lished and frequent follow-up visits should be scheduled to are at low risk for CHD, based on clinical judgment or monitor progress, modify the treatment plan as needed, and Framingham risk score.209 –211 provide encouragement. Effective therapy requires a long-term structured approach with continued support from the physician and other caregivers, particularly during periods Appropriate management requires identifying patients who of patient recidivism and weight regain.
need treatment, developing a realistic treatment plan, andimplementing a defined treatment strategy that can be Reducing energy intake is the cornerstone of weight modified as needed during long-term surveillance. The management therapy. Providing appropriate nutrition Practical Guide to the Identification, Evaluation, and counseling and the behavior modification therapy needed Treatment of Overweight and Obesity in Adults was to implement dietary changes within the setting of a busy developed by the North American Association for the outpatient practice is difficult if not impossible for most Study of Obesity in conjunction with the National Heart, physicians because they do not have the time or expertise Lung, and Blood Institute.212 Suggested guidelines from to provide this kind of care. Therefore, referral to a the guide for selecting among different weight loss treat- reputable weight loss program or experienced dietitian ment options, based on disease risk, are shown in Table 7.
should be considered, if these resources are available.
A typical clinical consultation involves a physician's Additional therapy with weight loss medications or bari- giving advice without adequate consideration of the pa- atric surgery can be useful in properly selected patients.
Obesity and Diabetes Educational Council (Roche); Enteromedics Takeda Pharmaceutical; Johnson&Johnson Dr Steven N. Blair Abbott Laboratories; Human Masterfoods; The Sugar Life Fitness International; Jenny Craig; Kinetics; McNeil Consumer & Bally Total Fitness Sports Medicine; Specialty Pharmaceuticals, Inc; Sherbrooke Capital; Miavita; International Masterfoods; WESTAT Life Sciences Institute Center for HealthPromotion; Healthetech; Westport Realty;Ruder Finn Dr David B. Allison Alabama Agricultural Land Grant American Oil Chemists Air Canada; Archer Daniels Midland; Alliance; Coca-Cola; General Mills; Society; Bristol Myers Coca-Cola; Cytodyne Technologies Inc; Gerber Foundation; International Squibb/Mead Johnson; Entelos; FTC; Fertin Pharma A/S; FDA; Life Sciences Institute; Federation of American Genome Explorations; Gibson, Dunn Societies of Experimental &Crutcher LLP; International Food M&M Mars; Merck; National Biology; Health Learning Information Council; Kraft Foods; Ligand Alliance for Research on Systems; Institute for the Pharmaceuticals; Lilly Research Labs; Schizophrenia and Affective Lockheed Martin; Maynard, Cooper & Disorders; NIH; NSF; Ortho-McNeil Gale, LLP; McKenna & Duneo, LLP; Pharmaceuticals; Pfizer Central Nutricia; NutriPharma; Parenti, Falk, Waas, Research; Proctor & Gamble; Hernandez & Cortina; Paterson, SlimFast Foods Company MacDougall; Pinnacle; Rand Corporation;Research Testing Laboratories; Rexall; RWJohnson Pharmaceutical ResearchInstitute; United Soybean Board; UnitedStates Postal Service; VeteransAdministration; Wilentz, Goldman &Spitzer.
Sanofi Synthelabo; Transneuronix; McNeil Specialty Products; Roche; Lilly This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit.
Klein et al
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Matrix-associated stem cell transplantation (mast) in chondral defects of the 1st metatarsophalangeal joint is safe and effective—2-year-follow-up in 20 patients

FAS-937; No. of Pages 6 Contents lists available at Foot and Ankle Surgery Matrix-associated stem cell transplantation (MAST) in chondral defects of the 1st metatarsophalangeal joint is safe and effective—2-year-follow-up in 20 patients Martinus Richter MD, PhDStefan Zech MD, Stefan Andreas Meissner MD Department for Foot and Ankle Surgery Rummelsberg and Nuremberg, Germany


bioavailability is used to describe the fraction of an administered reaches the , one of the principal . By definition, when a medication is administered [1] However, when a medication is administered (such as orally), its bioavailability decreases (due to incomplete absorption and ) or may vary from patient to patient (due to inter-individual variation). Bioavailability is one of the