Evaluation of Overweight and Obesity

W. Scott Butsch

Overweight and obesity have become major health concerns in modern postindustrial societies, affecting an estimated 69% of Americans older than the age of 20 years. Although recent data suggest the prevalence of overweight and obesity stabilized, there has been a disproportional increase in individuals with severe obesity as well as in racial/ethnic minorities. In addition, the long-term risks of becoming overweight and developing obesity (greater than 50% and 25% respectively), are significantly greater in those who develop obesity in adolescence. The personal and social costs are enormous, approaching $150 billion annually when medical complications, lost wages, and expenditures for weight reduction efforts are taken into account, not to mention the accompanying emotional pain, social stigmatization, and discrimination that may ensue. Excessive weight, through its promotion of the metabolic syndrome and insulin resistance, is a major risk factor for cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, and hypertension, and it is also associated with increased risks of stroke, heart failure, several types of cancer, and premature death. In addition, patients with obesity manifest heightened risks of impaired pulmonary function (including sleep apnea), osteoarthritis, gallbladder disease, venous thrombosis, and surgical complications.

The tasks for the primary physician in the evaluation of patients with excess weight include not only an attempt to identify etiologic factors but also a careful assessment of weight status and fat distribution as risk factors for major disease. This chapter focuses on the diagnostic evaluation (see Chapter 233 for the approach to treatment).

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 and 21)

Definitions (Table 10-1)

Obesity is defined as an excess of body fat. The standard classifications of overweight and obesity are based on body mass index (BMI) determinations, which approximate total body fat content and correlate with disease risk (Table 10-1):

Overweight—BMI of 25 to 29.9 kg/m²
Obesity—a BMI greater than 30 kg/m²
- Class I obesity (BMI 30.0 to 34.9 kg/m²)
- Class II obesity (BMI 35.0 to 39.9 kg/m²)
- Class III or severe obesity (BMI > 40 kg/m²)

Normal Physiology and Pathophysiology

The laws of thermodynamics ultimately determine body weight, which reflects the balance between energy intake and energy
expenditure. Changes in body weight represent an imbalance between intake and expenditure. Energy storage occurs largely in the form of adipose tissue; its regulation is necessary for normal growth and development as well as survival. Even small perturbations of adipose tissue through caloric restriction or overfeeding are tightly regulated and counteracted by a highly complex physiologic system involving the brain, digestive track, endocrine organs, muscle, and adipose tissue.

TABLE 10-1 Definition and Classification of Excess Weight

Class		BMI (kg/m²)	Waist Circumference^a	Relative Risk^b
Normal		18.5-24.9	Normal	Normal
			Increased	Increased
Overweight		25.0-29.9	Normal	Increased
			Increased	High
Obesity	Class I	30.0-34.9	Normal	High
			Increased	Very high
	Class II	35.0-39.9	Normal	Very high
			Increased	Very high
Severe obesity	Class III	40.0 +	All are increased	Extremely high
^a^aIncreased, >102 cm (40 inches) in men, >88 cm (35 inches) in women. ^b^bFor diabetes type 2, hypertension, coronary artery disease. BMI, body mass index. Adapted from Expert panel on the identification, evaluation, and treatment of overweight and obesity in adults. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med 1998;158:1855, with permission. Copyright © 1998, American Medical Association.

Caloric intake and energy expenditure are linked through hypothalamic regulation of appetite and metabolism. The hypothalamus integrates a complex and redundant set of afferent signals, including leptin, released from adipose tissue; norepinephrine from the autonomic nervous system; epinephrine, glucocorticoids, androgens, progesterone, estrogens, insulin, and pancreatic polypeptide from endocrine glands; ghrelin, peptide YY, glucagon-like peptide (GLP-1), oxyntomodulin, glucagon, cholecystokinin, somatostatin, and glucose from the gastrointestinal tract; and dopamine, gammaaminobutyric acid, ghlanin, opioids, growth hormone-releasing factor, somatostatin, and serotonin from the central nervous system. The efferent output from the hypothalamus controls energy expenditure and appetite by the release of alpha-melanocyte-stimulating hormone (alpha-MSH), norepinephrine, serotonin, neuropeptide Y, glucagon-like peptide I, thyrotropic hormone, and corticotropin-releasing hormone, which act on the autonomic nervous system and the thyroid gland. Increasingly appreciated as a factor in appetite control is the role of alpha-MSH on the melanocortin 4 receptor (MC4R), which, when stimulated, suppresses appetite.

Pathophysiology

Obesity represents a dysregulation of the normal physiology of energy balance, often a consequence of physical inactivity, especially in persons with an underlying disturbance in metabolism, appetite control, or dietary composition. In most instances, the etiology is multifactorial, although one factor may predominate. Susceptibility is influenced by genetic determinants that were once advantageous in regard to evolution, such as those that reduce energy expenditure or encourage the intake of energy-rich foods. However, such inherited traits can be counterproductive to good health in postindustrial societies, in which physical demands are greatly reduced and high-calorie food is plentiful and inexpensive.

Physical Inactivity

Physical inactivity emerges as a leading cause of obesity in modern society, underscored by the increasing prevalence of obesity despite a decline in average daily caloric intake. When daily life makes few physical demands, caloric needs drop precipitously, which leads to an epidemic of excess weight, even among those without major genetic susceptibility to weight gain. Some genetic variability in the propensity for exercise has been described, which may contribute to inactivity in some.

Metabolic Factors

Metabolic factors are important, genetically determined contributors to excessive weight and include resting energy expenditure, thermic effect of food, and exercise-induced energy expenditure. Among these, a reduction in energy utilization with exercise correlates the most strongly with risk for weight gain. From 9- to 30-fold variations have been observed. Because exercise-induced energy expenditure accounts for about 30% of total energy demand, any genetic propensity for reduced energy expenditure with exertion could substantially increase the risk for obesity.

Dietary Composition

Dietary composition actually plays a much smaller role than might be expected. In most persons, changing the percentages of dietary fat, protein, and carbohydrate without changing the number of calories consumed has little or no influence on the development of obesity. Diets high in fat contribute to obesity mostly because they are rich in calories, not because they are rich in fat. Similarly, sugar, which is often implicated in the development of obesity, contributes only in terms of overconsumption of calories. Protein appears to make less of a contribution. Despite claims to the contrary by those promoting weight loss diets, there is no evidence that dietary composition alone is a major determinant of obesity for the vast majority of persons. Almost all weight loss diets work by restricting total calories irrespective of composition (see Chapter 233). The timing of food intake may contribute modestly to obesity; eating once daily, particularly before going to bed, predisposes to the accumulation of adipose tissue in some persons.

Appetite Disturbances

Appetite disturbances have long been suspected as a cause of obesity. Many obese individuals appear to eat without satiety. This has led to intensive study of appetite regulation and its disruption. In some, there appears to be resistance to normal appetite controls, such as the appetite suppressant leptin, serum levels of which actually increase in obese subjects. In some obese persons, the postprandial production of appetite-suppressing gut hormone fragment polypeptide YY (PYY) is reduced compared with normal controls. In others, there is genetic alteration of the MC4R (see later discussion). In some animals, the effects of appetite suppressants can be overcome by providing easy access to palatable, energy-rich foods.

Genetic Factors

Genetic factors, as noted earlier, play a substantial role by influencing energy utilization, appetite, food preferences, and even propensity for physical activity. Genetic factors are estimated to account for nearly 55% to 85% of the variation of BMI; their importance is underscored by findings from studies of twins, families, and adoptees, which reveal a stronger correlation between BMI of adoptees and their biologic parents than between adoptees and their adopted parents. There are over 25 genetic syndromes associated with obesity which are commonly associated with cognitive deficits and an increased food intake (Table 10-1). MC4R deficiency is the most common monogenetic form of obesity, affecting less than 1% to 6% of children with severe obesity, and presents with hyperphagia and hyperinsulinemia. Leptin deficiency is less common but supports the hypothesis that these nonsyndromic monogenetic forms of obesity act through food intake, not energy expenditure. Polygenetic variants are more likely to explain the majority of case of obesity. Genome-wide association studies have begun to identify these variants, for example, the fat mass and obesity associated gene and its association with BMI. However, its effect is modest, confirming our beliefs that obesity is a highly polygenic and complex disorder.

Developmental and Environmental Factors

Developmental and environmental factors, manifested by parental influences and childhood environment, contribute to the development of adult obesity. As the age of the child increases, the influence of environment increases. At ages greater than 10 years, heredity becomes a less-dominant determinant of adult obesity, and environment increases in importance. Persons growing up in the current era of plentiful, inexpensive highcalorie fast food are at greater risk of obesity than are cohorts from earlier eras. Teenagers, especially, consume large amounts of such food, with potentially serious long-term consequences. Natural history studies find a strong relation between increased weight during the teenage and young adult years and risk of becoming frankly obese later in life. Those who become obese tend to remain obese their entire lives.

Psychological and Behavioral Factors

It has long been thought that obesity is an eating disorder; however, individuals with obesity do not overeat with any specific pattern. In addition, there is no known psychological explanation for why reactive hyperphagia develops in some persons as a response to emotional stress, whereas anorexia is the reaction of others. Considerable research has been unable to determine any particular personality organization or cluster of psychological defense mechanisms clearly linked to obesity. Nonetheless, psychological problems frequently contribute to the onset and perpetuation of obesity-inducing behavioral changes. Some individuals characteristically overeat in response to stress, loss, or frustration. Two behavioral eating disorders affect individuals with obesity: binge eating disorder (BED) and night-eating syndrome (NES). Those with the NES, characterized by insomnia, massive late-evening “refrigerator raids,” and morning anorexia, also experience particular emotional distress when they try to reform their eating behaviors. Usually, coinciding social stresses are present as well. The appetite disturbance associated with major depression may lead to either an increase or a decrease in weight.

Social Factors

Social factors are key determinants of the frequency and nature of feasts, timing of meals, role and meaning of food, types of foods consumed, and norms of appearance. In US society, excess weight occurs far more frequently among minorities and the socioeconomically disadvantaged than among others. Young African American and Hispanic women are 2.1 and 1.5 times, respectively, more likely to become obese than are young white women. Whether this difference represents dietary preference, socially motivated behavior, or interactional factors is unclear.

Clinical Presentation

Most cases of overweight and obesity occur independent of an underlying medical condition, although they may exacerbate or lead to illness. Onset of exogenous obesity is often evident by early adulthood and tends to persist. Those who are overweight by their adolescent years are at considerable risk of developing severe obesity by their early 30s. Persons with an underlying hereditary etiology usually manifest obesity before age 10 years. In 5% to 10% of adult cases, an underlying medical condition or medication that affects energy expenditure, fuel utilization, appetite, or physical activity may be responsible. Often, the mechanism is an effect on one of the substances involved in regulating energy intake or expenditure (see earlier discussion).

Pharmacologic Agents

Pharmacologic agents prescribed for clinical conditions other than obesity may cause weight gain. Beta-blockers and central sympatholytics (e.g., clonidine) can decrease metabolic rate and energy expenditure. Glucocorticosteroids cause hypertrophic obesity in a characteristic truncal pattern. Antidepressants, such as the tricyclics and selective serotonin reuptake inhibitors, and some antihistamines (e.g., cyproheptadine) act as appetite stimulants. Weight gain is also common with oral contraceptive use.

Endocrine Disturbances

Endocrine disturbances are more often the result, rather than the cause, of excess weight. However, hypothyroidism (see Chapter 104) has been found to account for up to 5% of cases in some series. Cushing’s syndrome is a rare cause and is usually accompanied by characteristic features of truncal obesity and peripheral muscle wasting. Stein-Leventhal syndrome—polycystic ovaries, absent menses, moderate hirsutism, and hyperinsulinism (see Chapter 112)—often goes unrecognized as an endocrinologic form of obesity; the precise mechanism of the obesity is unknown. Eunuchism may also be associated with obesity. Of great concern is the marked increase in frequency of insulin resistance and its attendant metabolic syndrome, characterized by hyperinsulinism, elevated triglycerides, and low high-density lipoprotein (HDL) cholesterol, all important risk factors for diabetes, hypertension, and cardiovascular disease. Serum insulin and triglyceride levels are elevated, and HDL cholesterol is reduced.

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