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The Merck Manual of Diagnosis and Therapy   hyperlink to list of sections
Section 1. Nutritional Disorders   hyperlink to list of chapters in current section
Chapter 5. Obesity
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Obesity: The excessive accumulation of body fat.

Traditionally, obesity has been defined as a body weight of > 30% above ideal or desirable weight on standard height-weight tables (see Table 1-5). Now, it is usually defined in terms of the body mass index (BMI)--weight (in kilograms) divided by the square of the height (in meters).


The prevalence of obesity in the USA is high and rising higher. In the past decade, the overall prevalence rose from 25 to 33%, an increase of 1/3. Prevalence varies significantly by sex, age, socioeconomic status, and race (see also Obesity in Ch. 275). Prevalence is 35% among women and 31% among men, and it more than doubles between the ages of 20 and 55. Among women, obesity is strongly associated with socioeconomic status, being twice as common among those with lower socioeconomic status as it is among those with higher status. Although prevalence among black and white men does not differ significantly, obesity is far more common among black than among white women, affecting 60% of middle-aged black women compared with 33% of white women.


In one sense, the cause of obesity is simple--expending less energy than is consumed. But in another sense, it is elusive, involving the regulation of body weight, primarily body fat. How this regulation is achieved is not yet fully understood.

Weight is regulated with great precision. For example, during a lifetime, the average person consumes at least 60 million kcal. A gain or loss of 20 lb, representing 72,000 kcal, involves an error of no more than 0.001%. Regulation of body weight is believed to occur not only in persons of normal weight but also among many obese persons, in whom obesity is attributed to an elevation in the set point around which weight is regulated. The determinants of obesity can be divided into the genetic, the environmental, and the regulatory.

Genetic determinants: Recent discoveries have helped explain how genes may determine obesity and how they may influence the regulation of body weight. For example, mutations in the ob gene have led to massive obesity in mice. Cloning the ob gene led to the identification of leptin, a protein coded by this gene; leptin is produced in adipose tissue cells and acts to control body fat. The existence of leptin supports the idea that body weight is regulated, because leptin serves as a signal between adipose tissue and the areas of the brain that control energy metabolism, which influences body weight.

The extent of genetic influences on human obesity has been assessed by twin, adoption, and family studies. In the first studies, of twins, the heritability of the BMI was estimated to be very high, about 80%, and this value is still frequently cited. The results of adoption and family studies, however, agree on a heritability of about 33%, which is generally viewed as more reasonable than that of the twin studies. Genetic influences may be more important in determining regional fat distribution than total body fat, particularly the critical visceral fat depot (see below).

Environmental determinants: The fact that genetic influences account for only 33% of the variation in body weight means that the environment exerts an enormous influence. This influence is dramatically illustrated by the marked increase in the prevalence of obesity in the past decade.

Socioeconomic status is an important influence on obesity, particularly among women. The negative correlation between socioeconomic status and obesity reflects an underlying cause. Longitudinal studies have shown that growing up with lower socioeconomic status is a powerful risk factor for obesity. Socioeconomic factors are major influences on both energy intake and energy expenditure.

A large food intake is associated with obesity. For many years, it was believed that obscure metabolic disturbances caused obesity and that food intake was normal. However, the doubly labeled water method, using stable isotopes of hydrogen and oxygen, shows that obese persons have a large energy expenditure, which requires in turn a large food intake. Furthermore, this large food intake usually includes a large fat intake, which independently predisposes to obesity.

A sedentary lifestyle, so prevalent in Western societies, is another major environmental influence promoting obesity. Physical activity not only expends energy but also helps control food intake. Animal studies suggest that physical inactivity contributes to obesity by a paradoxical effect on food intake. Although food intake increases as energy expenditure increases, food intake may not decrease proportionately when physical activity falls below a minimum level; restricting activity may actually increase food intake for some people.

Regulatory determinants: Pregnancy is a major determinant of obesity in some women. Although most women weigh only a little bit more a year after delivery, about 15% weigh 20 lb more with each pregnancy.

An increase in fat cells and adipose tissue mass during infancy and childhood--and for some severely obese persons, even during adulthood--predisposes to obesity. This increase can result in five times as many fat cells in obese persons as in persons of normal weight. Dieting reduces only fat cell size, not fat cell number. As a result, persons with hypercellular adipose tissue can reduce to a normal weight only by markedly depleting the lipid content of each cell. Such depletion and the associated events at the cell membrane may set a biologic limit on their ability to lose weight and may explain their difficulty in reducing to a normal weight.

Brain damage caused by a tumor (especially craniopharyngioma) or an infection (particularly affecting the hypothalamus) leads to obesity in a very small number of persons. Whatever the other determinants of obesity, the final common pathway to caloric balance lies in behavior mediated by the CNS.

Drugs have recently been added to the list of determinants of obesity because of the increased use of pharmacotherapy. Weight gain can be produced by steroid hormones and four major classes of psychoactive drugs--traditional antidepressants (tricyclics, tetracyclics, monoamine oxidase inhibitors), benzodiazepines, lithium, and antipsychotic drugs. Limiting the use of drug treatment to prevent weight gain may present a serious therapeutic dilemma.

Endocrine factors have been traditionally viewed as important determinants of obesity. Hyperinsulinism from pancreatic neoplasms, hypercortisolism from Cushing's syndrome, the ovarian dysfunction of polycystic ovary syndrome, and hypothyroidism have all been implicated in some cases of obesity, but endocrine determinants affect only a very small number of obese persons.

Psychologic factors, once viewed as important determinants of obesity, are now believed to be limited largely to two deviant eating patterns. Binge eating disorder is characterized by the consumption of large amounts of food in a short time with a subjective sense of loss of control during the binge and distress after it (see Ch. 196). Unlike patients with bulimia nervosa, these patients do not engage in compensatory behaviors, such as vomiting; thus their binges contribute to excessive caloric intake. Binge eating disorder is believed to occur in 10 to 20% of persons entering weight reduction programs. The night-eating syndrome consists of morning anorexia, evening hyperphagia, and insomnia. It occurs in about 10% of persons seeking treatment for obesity.

Symptoms and Signs

The symptoms and signs of obesity consist of the immediate consequences of the large adipose tissue mass. Prominent among them is sleep apnea, a seriously underdiagnosed disorder, characterized by moments during sleep when breathing ceases, as often as hundreds of times a night (see Sleep Apnea Syndromes in Ch. 173).

In the obesity-hypoventilation syndrome (pickwickian syndrome), impairment of breathing leads to hypercapnia, a reduced effect of CO2 in stimulating respiration, hypoxia, cor pulmonale, and a risk of premature death.

Obesity may lead to orthopedic disturbances of weight-bearing and non-weight-bearing joints. Skin disorders are particularly common; increased sweat and skin secretions, trapped in thick folds of skin, produce a culture medium conducive to fungal and bacterial growth and infections.

The level of general psychopathology, as assessed by psychologic tests, does not differ between persons who are obese and those who are not. However, for some young women in upper and middle socioeconomic groups, psychologic problems are linked to obesity. The current view is that the intense prejudice and discrimination to which obese persons are subjected is the source of these problems. In addition to the eating disorders noted above, these problems include disparagement of body image, a condition in which persons feel that their body is grotesque and loathsome. These women believe that others view them with hostility and contempt, which makes them self-conscious and impairs social functioning.


Obesity represents one end of a distribution curve of body fat, with no physiologically defined cutoff point. For practical purposes, the eyeball test is sufficient: If a person looks fat, the person is fat. For a more quantitative measure of obesity, BMI is used, with obesity arbitrarily defined as a BMI of > 27.8 for men and > 27.3 for women.

Some special distributions of body fat are important in the diagnosis of certain disorders--for example, the buffalo hump of hyperadrenocorticism and the peculiar accumulation of fluid in hypothyroidism.

Recognizing the significance of body fat distribution, particularly of the visceral fat depot, has measurably advanced the understanding of obesity. Clinically, this distribution is assessed by the waist/hip ratio, with high-risk upper body obesity defined as a ratio of > 1.0 for men and > 0.8 for women. Risk, however, is directly proportional to the size of the ratio, independent of sex; the greater mortality and morbidity of men is a function of their greater waist/hip ratio.


The deleterious consequences of obesity are considerable. Recent estimates attribute 280,000 deaths a year in the USA to "overnutrition," making it second only to cigarette smoking as a cause of death.

Many of the metabolic disorders of obesity are believed to be caused by abdominal visceral fat, which leads to an increased concentration of free fatty acids in the portal vein and, consequently, to decreased hepatic insulin clearance, insulin resistance, hyperinsulinemia, and hypertension. This sequence of events leads to diabetes, dyslipidemias, and, ultimately, coronary artery disease.

The complications of obesity highlight a paradox. Most of the persons receiving treatment for obesity are women, who are far less likely to suffer from its complications than are men. Men who need treatment are not receiving it.

Prognosis and Treatment

The prognosis for obesity is poor; untreated, it tends to progress. With most forms of treatment, weight can be lost, but most persons return to their pretreatment weight within 5 yr.

In recent years, the goals and methods of the treatment of obesity have changed radically as a result of two developments. The first is evidence that a modest weight loss, 10% or perhaps even 5% of body weight, is sufficient to control, or at least improve, most complications of obesity. Therefore, there is no reason to pursue the traditional goal of attaining an ideal body weight, which is so seldom attained and, if attained, is so rarely maintained. The "10% solution" has become the goal of most treatment programs.

The second development, derived from the poor maintenance of weight loss during treatment, is a move from a goal of weight loss to one of weight management, achieving the best weight possible in the context of overall health.

Weight management programs can be divided into three major categories.

Do-it-yourself programs are the resource for most obese persons who seek help. A physician may help obese patients by becoming familiar with these programs. They include self-help groups, such as Overeaters Anonymous and Take Off Pounds Sensibly (TOPS); community-based and work-site programs; books and magazine articles; and weight loss products, such as meal replacement formulas.

Nonclinical programs are popular commercial enterprises that have a structure created by a parent company and weekly meetings conducted by variably trained counselors, supplemented by instructional and guidance materials prepared in consultation with health care professionals. These programs usually provide no more than 1 yr of treatment, and their costs vary from approximately $12/wk for Weight Watchers to $3,000/6 mo of treatment in some programs. The effectiveness of commercial programs is hard to evaluate because they publish few statistics and have high dropout rates. Nevertheless, their ready availability has made them popular. Physicians can assist patients by helping them select programs with sensible low-fat diets and an emphasis on physical activity.

Clinical programs are provided by licensed health care professionals, often as part of a commercial weight loss enterprise but also in solo or group private practice.

Weight management programs make use of four modalities: diet and nutritional counseling, behavior therapy, drugs, and surgery.

Diet: Traditional dieting is now rarely prescribed; long-term habit change is emphasized instead. Most programs teach clients how to make safe, sensible, and gradual changes in eating patterns. Changes include increased intake of complex carbohydrates (fruits, vegetables, breads, cereals, and pasta) and decreased intake of fats and simple carbohydrates. Very low calorie diets, providing 400 to 800 kcal/day, have declined in popularity, as it has become apparent how rapidly patients regain the large amounts of weight they have lost.

Behavior therapy: The basis of most nonclinical (commercial) weight loss programs is behavior therapy. It is based on behavioral analysis, which considers the behavior to be changed, its antecedents, and its consequences. The primary behavior to be changed is eating, with efforts to slow the rate of eating. Next is an effort to change the antecedents of eating, ranging from relatively remote ones (eg, shopping for food) to more immediate ones (eg, too readily available high-calorie snacks in the home). The third step is reinforcing these behaviors. Self-monitoring, with detailed record keeping, is used to determine which behaviors should be modified and reinforced. Nutrition education is increasingly important in these programs, as are measures to increase physical activity. Cognitive therapy is being applied to overcome the self-defeating, maladaptive attitudes toward weight reduction common among obese persons and to provide training in relapse prevention for the usual lapses experienced in any program of weight management.

Drugs: The many benefits of even modest weight loss and the difficulty in maintaining weight loss have rekindled interest in the pharmacotherapy of obesity, especially since the newer drugs have less potential for abuse than those used in the 1970s. However, the recent discovery of widespread valvular heart disease in patients who received fenfluramine alone or in combination with phentermine (often referred to as fen-phen) has cast a pall over drug therapy for obesity. Fenfluramine should no longer be used, and what effect the unfortunate disclosure will have on the prescription of appetite suppressant drugs is unclear. Sibutramine has recently been approved as an appetite suppressant, but experience with it is limited. Over-the-counter drugs are generally harmless, questionably effective, and best avoided.

Surgery: For persons with very severe obesity (BMI > 40) and those with less severe obesity and serious or life-threatening complications, surgical procedures are the treatment of choice. They can result in large weight losses that are usually well maintained for > 5 yr. The most common operations--vertical banded gastroplasty and gastric bypass--radically reduce stomach volume by creating a gastric pouch of no more than 25 mL in volume.

Weight loss after surgery is rapid at first, slowing gradually over a period of 2 yr. It is directly proportional to the extent of obesity and usually varies between 40 and 60 kg. The weight loss is accompanied by marked improvement in medical complications as well as in mood, self-esteem, body image, activity levels, and interpersonal and vocational effectiveness. In experienced hands, preoperative and operative mortality is usually < 1% and operative complications < 10%.

Copyright 1995-2000 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.

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