Body fat percentage, body mass index, skin thicknesses, and anthropomorphic measures

A reasonable goal for weight-loss in the setting of a medical treatment program is approximately 0.9-1.5 kg/wk. The concept that the weight-loss goal for each subject must be individualized and cannot be unilaterally based on standard weight-for-height norms is becoming increasingly apparent.

One must consider the family's weight, as well as the patient's weight and cultural, ethnic, and racial background in setting individualized goals of weight loss. In a study of approximately 200 obese black women, the Obesity Reduction Black Intervention Trial (ORBIT) investigated whether greater weight loss could be achieved with a culturally adapted weight-loss program than with a more general health program.^[22]

The women were randomly divided into a general health program or a 6-month culturally adapted program aimed at altering the women's dietary and physical activity patterns (followed by 1 year of maintenance intervention). Women in the latter group lost significantly more weight than did participants in the general program, although the report also found that, despite this success, the average weight loss in the culturally adapted program was still relatively modest and that the amount of weight loss varied greatly among the women in the program.

Like all chronic medical conditions, effective management of obesity must be based on a partnership between a highly motivated patient and a committed team of health professionals, including the physician, psychologists or psychiatrist, physical and exercise therapists, dietitians, and other subspecialists, depending on the comorbidities of the individual patient.

Results of weight-loss management

Results of most weight loss management programs are dismal. On average, participants in the best weight-loss programs lose approximately 10% of their body weight, but people generally regain two thirds of the weight lost within a year, and they regain almost all of it within 5 years.

When defined as sustained weight loss over a 5-year follow-up period, the success of even the best medical weight-loss programs is next to nil. Most available data indicate that, irrespective of the method of medical intervention, 90-95% of the weight lost is regained in 5 years.

In general, body weight and body fat generally tenaciously regulated. Available data suggest that a loss of approximately 10% of body weight in subjects who are obese (BMI < 40) is associated with virtually maximal benefits regarding obesity-elated comorbidities; therefore, further attempts at weight loss beyond this level are generally spurred by cosmetic considerations that may be not only unrealistic but also potentially dangerous. This possibility is the basis of a shift in paradigms in the medical management of obesity from a goal of massive weight loss to a goal of maintaining the highest weight possible while still eliminating obesity-related comorbidities or reducing them to minimum.

A study by Rock et al found that a structured weight loss program resulted in greater risk reduction than usual care.^[23]

Childhood obesity

For childhood obesity,^{[24, 25, 26]} the goal is to reduce the rate of weight gain to fit the profile expected based on normal growth curves. The intent here is not to cause weight loss.

The basic principles of management include (1) modifying diet, (2) increasing appropriate physical activity and exercise, (3) reducing time spent in sedentary activities (eg, watching television), and (4) modifying behavior.

Added to these principles is medication therapy. However, such therapy is still rudimentary in the management of pediatric obesity, and close combination with all the aforementioned modalities is required to achieve substantial and sustained weight loss. At the present, orlistat is the only medication the US Food and Drug Administration (FDA) has approved for use as an adjunct for weight loss in adolescents.

Starvation is a caloric intake of less than 200 kcal/d and is not medically indicated. Starvation is potentially dangerous and can lead to clinically significant starvation ketosis; electrolyte derangements; vitamin, mineral, and other micronutrient deficiencies; and a marked potential for morbidity and mortality. Starvation is not validated as an effective method of achieving substantial and sustained weight loss.

Achieving a caloric deficit is still the most important component to achieving sustained weight loss. However, the considerable variance in individual energy expenditures and compliances to calorie-deficient plans make it difficult to reliably predict how much weight an individual subject may lose.

Among the caveats are the fact that energy expenditure is related to body weight; about 22 kcal/kg of energy required for basal maintenance of 1 kg of weight in a typical adult. Therefore, obese subjects tend to reduce their energy expenditure as they lose weight, dampening the effect of caloric deficits as weight loss progresses.

Presumably because of their greater lean mass proportions, men tend to lose more weight than women do when caloric deficits are similar.

Because of their lowered energy expenditure, older subjects have increased difficulty is achieving sustained weight loss. The estimated reduction in energy expenditure is 100 kcal per decade after the age of 30 years.

Dennis et al found that in overweight and obese middle-aged and older adults on a hypocaloric diet, drinking water before each main meal aided weight loss. In 48 adults aged 55-75 years with a BMI of 25-40 kg/m², those who consumed 500 mL of water prior to each daily meal had a 44% greater decline in weight over 12 weeks than did individuals on a hypocaloric diet without premeal water consumption.^[27]

Very–low-calorie diets

Very–low-calorie diets (VLCDs) are best used in an established, comprehensive program. VLCDs involve reducing caloric intake to 800 kcal/d or less. When used in optimal settings, they can achieve weight loss of 1.5-2.5 kg/wk, with a total loss of as much as 20 kg over 12 weeks. No good-quality evidence suggests that a daily calorie intake of less than 800 kcal/d achieves any additional weight loss.

Use special caution whenever VLCDs are prescribed to children, adolescents, or elderly subjects. Use is contraindicated in pregnancy and in protein-wasting states; clinically significant cardiac, renal, hepatic, psychiatric, or cerebrovascular disease; or any other chronic disease. VLCDs are associated with profound initial weight loss, much of which is from lean mass loss in the first few weeks. However, this loss rapidly ceases, and weight-loss velocity then flattens. Although these diets associated with notable short-term weight loss sometimes less than 15% of baseline weight and though they are associated with improved blood pressure and glycemic control, they cannot be sustained longer than 3-6 months. Compliance beyond a few weeks is poor, and close supervision is required to avoid mishaps.

Unless a long-term maintenance calorie-deficit program is developed and adhered, to recidivism after the diet is stopped is rapid. Most subjects quickly regain all the weight they lose and often gain more.

Among the major complications to monitor are hair loss, skin thinning, hypothermia, cholelithiasis, and electrolyte derangement. VLCDs have little or no utility in long-term weight management and are probably best used as stop-gap measures before bariatric surgery or a long-term comprehensive weight-loss program in subjects with very severe or morbid obesity and associated comorbidities (BMI ≥50).

Conventional diets

Conventional diets can be broadly subclassified as (1) balanced, low-calorie diets (or reduced portion sizes), (2) low-fat diets, (3) low-carbohydrate diets, (4) midlevel diets (eg, Zone diet in which the 3 major macronutrients [fat, carbohydrate, protein] are eaten in similar proportions of 30-40%), and (5) fad diets.

Balanced LCDs or reduced portion sizes diets are the types that dietitians and other weight-management professionals most commonly prescribe. These diets underlie most of the popular, commercial weight-loss programs such as those advocated by Jenny Craig, Weight Watchers, Take Off Pounds Sensibly (TOPs), and Overweight Anonymous. The basic premise involves obtaining a detailed dietary inventory of the subject, which is used to estimate his or her mean daily caloric intake.

A reasonable goal for the caloric deficit is based on the new goal for total daily calories. Meal plans are then devised to provide this total in ≥3 divided meals throughout the day. Although the meals may be based on regular, everyday foods (with which strategies for effective reduction of portion sizes become central), meal-replacement shakes, bars, prepackaged meals, frozen entrees, and other meals also have adequate amounts of the major macronutrients based on the food pyramid from the US Department of Agriculture and recommended daily allowances (RDAs). These sources also have adequate micronutrients and trace elements. Because alcohol, sodas, most fruit juices, and highly concentrated sweets are generally calorie dense and nutrient deficient (empty calories), these are generally prohibited or reduced to the minimum.

Low-calorie diets involve a caloric intake of 800-1200 kcal/d and are associated with a mean weight loss of 0.4-0.5 kg/wk, with a total loss of 6-8 kg in ideal settings. With any low-calorie diet, maintaining intake of protein with high biologic value of ≥1 g/kg is vital to preserve lean body mass. Major potential complications to watch for include vitamin deficiency, starvation ketosis, electrolyte derangements, and cholelithiasis. Although these diets are useful for short-term weight loss, none alone is associated with reliable, sustained weight loss.

Normal-calorie diets involve diets with a caloric intake greater than 1200 kcal/d. The aim with this type of diet is to reduce the caloric intake by 500-1000 kcal/d from the patient's current dietary intake. The suggested composition for the best-validated dietary programs are protein intake of 0.8-1.5 g/kg of body weight (not to exceed 100 g/d), 10-30% of total calories from fat (preferably ≥90% as polyunsaturated fat and < 10% as saturated fat), carbohydrate intake of ≥50 g/d, and water intake of ≥1 L. Ensure that the dietary plan provides adequate micronutrients and macronutrients based on RDAs.

Low-carbohydrate diets have become popular in the past few decades, with the Atkins diet being the most popular. Little rigorous scientific data supports the use of the Atkins diet. It is a high-protein and/or high-fat, very-low-carbohydrate diet that induces ketosis. The very low carbohydrate content is critical in inducing short-term weight loss in the first 2-4 weeks; this is largely due to fluid mobilization. Ketone bodies tend to be generated with daily dietary carbohydrate intake of < 50 g, force sodium diuresis, which causes most of the short-term weight loss. No robust data about the safety or long-term effectiveness of this diet are available. The premise of the diet is that caloric intake as protein is less prone to fat storage than the equivalent caloric intake as carbohydrate; however, no physiologic data support this premise.

Data on the long-term effects of a high-protein in rodents causes concern because these diets may be associated with a reduced life span and predisposition to neoplasia.

In 2 randomized trials weight loss with Atkins-type diets were compared with conventional low-fat or balanced calorie-deficit diets. Although the Atkins-type diet had the greatest initial weight loss, weight loss became similar within 1 year. Furthermore, though lipids did not appear to be deleteriously affected, follow-up was only about 1 year, and noncompliance rates in the Atkins-type group was close to 50%.

The South Beach diet is another low-carbohydrate diet. This program is more liberal than the Atkins diet in its carbohydrate allowance; therefore, compliance rates are enhanced. The South Beach diet distinguishes between what it considered to be good and bad carbohydrates on the basis of their glycemic index. Although the relevance and importance of the glycemic index is controversial, the diet encourages increased fiber intake, which is associated with lowered weight even when total caloric intake is relatively unchanged. Low-glycemic index diets plus modest increase in protein intake are better at helping maintain weight loss.^[28]

The National Weight loss database, tracks indices and predictors in subjects with sustained (≥5 y) weight loss of 15% or greater. The data indicate that sustained compliance to diet programs is by far a more important predictor of sustained weight loss than consistently increased levels of physical activity. Caloric deficits are more important than any specific composition of dietary macronutrient. When types of diets are compared, low-fat diets are better than low-carbohydrate diets in achieving sustained weight loss (probably because of generally improved compliance).

Dansinger and colleagues (2005) compared the Zone, Ornish, and Atkins diets and a typical balanced, calorie-restricted (Weight Watchers) diet.^[29] The Ornish diet, very-low-fat diet, and the Atkins diets had the poorest compliance rates. The researchers observed no significant differences in weight loss based on the diet. Compliance and caloric deficits were more important predictors of weight loss and improvement in cardiovascular risk surrogates than specific dietary composition. However, a recent study found low-carbohydrate and low-fat diets equally efficacious in inducing weight loss but that fuel partitioning may impact cardiovascular markers differently.^[30]

For subjects who decide to use a low-carbohydrate diet, they should choose heart-healthy sources of fat (monounsaturated fats, polyunsaturated fats, and fats rich in omega 3 fatty acids rather than saturated fat) and protein (fish, nuts, legumes, and lean poultry rather than pork chops, steak, or mutton).

Exercise programs

Before receiving an exercise-program prescription, patients should undergo screening for cardiovascular and respiratory adequacy. Any clinically significant anomalies found require full evaluation by appropriate subspecialist physicians, and only after these issues are adequately managed and stabilized should an active exercise program be begun.

Aerobic isotonic exercise is of the greatest value for subjects who are obese. The ultimate minimum goal should be to achieve 30-60 minutes of continuous aerobic exercise 5-7 times per week.

Anaerobic isometric exercise, including resistance training, can be cautiously added as an adjunct after the aerobic goal described above is achieved.

Exercise is vital to any weight-management program because it helps build muscle mass, increasing metabolic activity of the whole-body mass. Exercise also helps reduce body-fat proportions and decreases the amount of compensatory muscle mass loss that is typical in the setting of weight loss. Although most laypersons may be unable to sustain enough regular exercise to achieve weight loss, consistent moderate exercise is important in maintaining weight and in improving overall cardiorespiratory fitness.

A study by Goodpaster et al showed that patients with severe obesity who introduced exercise concurrently with or after dietary intervention had significant weight loss and modification of cardiometabolic risk factors.^[31] Furthermore, a study by Hankinson et al indicated that benefits of exercise in young age may translate into benefits beyond, particularly in young women.^[32] This information is useful for patients and physicians who may be discouraged by the initial inability of patients to engage in exercise.

A combination of weight loss and exercise is better than either alone in improving physical fitness.^[33]

Behavioral changes

This treatment requires a trained professional to have an in-depth discussion with the patient regarding the changes required, subsequent to a detailed inventory of the patients' daily activities. This inventory is used to identify activities, cues, circumstances, and practices that favor nonmeal eating and snacking. An individualized plan to change these practices is then developed in conjunction with the subject. The effectiveness of this modality depends on both a highly motivated subject and a dedicated counselor who is willing to maintain long-term follow-up.

A sufficient amount of human sleep favorably impacts maintenance of fat-free mass during times of decreased energy intake. On the contrary, insufficient sleep would undermine the body's ability to limit expansion of fat mass. A healthy sleep pattern would be important to harness weight loss benefits from other interventions.^[34]

A 3-month intervention (face-to-face education sessions) led to significant weight loss and better health-related outcomes in fathers and improved eating and physical activity among children.^[35] Involvement of fathers in the weight management of children needs to be encouraged and further explored.

Not many medications are available for the treatment of obesity, and those that are available have minimal long-term effectiveness.

The increasing knowledge that has come on the heels of the discovery of leptin by Friedman and colleagues in 1994 has spurred a whirlwind of research, with several potential pharmaceuticals now being evaluated in various phases of clinical trial.

Murray et al first reported on a sequence variant within the leptin gene that enhances the intrinsic bioactivity of leptin, leading to reduced weight rather than obesity.^[36] This sequence variant within the leptin gene is associated with delayed puberty as well.

The major groups of drugs used to manage obesity are (1) centrally acting medications that impair dietary intake, (2) medications that act peripherally to impair dietary absorption, and (3) medications that increase energy expenditure.

Standards for the development of obesity medications are necessarily high because most persons who are obese are fairly healthy in the short-term and must take these medications for extended periods (possibly for the rest of their lives).

The history of obesity medications is replete with numerous disasters that have taught us caution in the use of this group of medicines.

Among the initial medications used for obesity management were amphetamine, methamphetamine, and phenmetrazine. These were all withdrawn because of their high potential for abuse.

Other former antiobesity medications are thyroid hormone (which caused hyperthyroidism with its attendant sequelae), dinitrophenol (which caused cataracts and neuropathy), rainbow pills (which are a mixture of digitalis and diuretics [which caused deaths from arrhythmias and electrolyte derangements]), aminorex (which caused pulmonary hypertension), and collagen-based VLCDs (which caused sudden deaths).

D-fenfluramine was withdrawn because of problems with cardiac valvulopathies and primary pulmonary hypertension (PPH).

Fluoxetine is not approved for use in achieving weight loss, but it has been known to cause minimal weight loss as an adverse effect, which is sometimes exploited.

Fenfluramine, although effectively used in combination with phentermine, was withdrawn in 1997 (along with D-fenfluramine) because of the potential for adverse cardiac, valvular, and pulmonary hypertensive effects.

The combination of fenfluramine and phentermine was used in some long-term trials with fair results.

The combination of low-dose phentermine and topiramate in conjunction with office-based lifestyle intervention might improve the success rate in the treatment of obesity.^[37]

Diethylpropion (25 mg 3 times/d [tid]) and phentermine are available in the US for short-term use.

Phendimetrazine (30 mg/d) and benzphetamine (20-50 mg tid) are not longer available in the US.

Mazindol, which was withdrawn from the US market in 2001, was another drug that was only for short-term use (1 mg tid).

Phenylpropanolamine, which was also for short-term use (25 mg tid), was recalled from the US market. Phenylpropanolamine is an alpha-adrenoreceptor agonist. Some reports suggested a potential association between the use of phenylpropanolamine and ischemic stroke; therefore, this drug should be used with caution in elderly individuals and only after carotid atherosclerosis is excluded.

Methylphenidate is not approved by the FDA for obesity management, although several anecdotal reports have described it as having variable success for this purpose.^[38]

Sibutramine (Meridia) is a centrally acting appetite suppressant that inhibits reuptake of noradrenalin, serotonin, and dopamine.^[39] The Sibutramine Trial of Obesity Reduction and Maintenance (STORM) revealed that a 9% weight loss persisted for as long as 18 months after the start of therapy. Sibutramine is fraught with adverse cardiovascular outcomes, and the drug has been withdrawn from the market in Europe. The US FDA is asking its advisory panel to review sibutramine safety in light of the recently published Sibutramine Cardiovascular Outcomes (SCOUT) trial.^[40]

On October 8, 2010, Abbott and the US Food and Drug Administration (FDA) announced sibutramine (Meridia) is being withdrawn from the market because of increased risk of myocardial infarction (MI) and stroke. Europe suspended sibutramine from the market earlier this year.

The FDA requested the market withdrawal after reviewing data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT). SCOUT was initiated as part of a postmarket requirement to look at cardiovascular safety of sibutramine after the European approval of this drug. The trial demonstrated a 16% increase in the risk of serious heart events, including nonfatal MI, nonfatal stroke, the need to be resuscitated once the heart stopped, and death, in a group of patients given sibutramine and another given placebo. A very small difference (2.5%) in weight loss was noted between the placebo group and the group that received sibutramine.^[41]

Orlistat is the only FDA-approved antiobesity drug on the market. Orlistat (Xenical) blocks the action of pancreatic lipase, reducing triglyceride digestion and, thus, absorption.^[42] Two major clinical trials showed sustained weight loss of 9-10% over 2 years.

Ephedrine and caffeine are second-line options in the medical management of obesity. They both act by increasing energy expenditure, but they are associated with the potential for tachycardia, hypertension, and palpitations. These medications are associated with more weight loss when used in combination than when used alone. They cause 25-40% of their weight loss by inducing thermogenesis, but they also decrease food intake, which accounts for 60-75% of the weight-loss effect.

Although not FDA approved for this purpose, several selective serotonin reuptake inhibitors (SSRIs; eg, fluoxetine, paroxetine) may cause anorexia as one of their major adverse effects. Some of these medications have been used as adjuncts in the medical management of obesity, with variable success.

Bupropion, which is licensed for use as an antidepressant and in smoking cessation, is associated with minimal to moderate weight loss.^[43] Preliminary reports have suggested similar findings with venlafaxine.

Topiramate, licensed as an adjunctive antiepileptic agent, was associated with profound weight loss of as much as 15-18% of the baseline weight. The amount of weight loss appears to be greater with greater baseline weights. The exact mechanism of this effect is being actively investigated. Although the degree of efficacy is exciting, the propensity for adverse effects, especially CNS effects such as drowsiness, paresthesias, memory loss, and confusion, is concerning. Doses for weight management are lower than those for seizure management (usually 25-100 mg/day in divided doses). Doses >200 mg/d are rarely tolerated when administered for weight loss. Topiramate does not have an FDA-approved indication for weight loss at this time.^[44]