Obesity is a major health problem world wide. The number of overweight men and women in the United States has risen steadily since 1960, with a staggering 54.9% of the adult population being overweight in the most recent epidemiologic reviews.39, 57, 58 In this country and in many others, excess body weight is especially evident in some minority groups and among those with lower incomes and less education. This excess in body weight substantially increases the risk of morbidity from hypertension; dyslipidemia; type 2 diabetes mellitus; coronary artery disease; stroke; gallbladder disease; osteoarthritis; sleep apnea and respiratory problems; and endometrial, breast, prostate, and colon cancers. Indeed, the risk for death from all causes, cardiovascular disease, cancer, or other diseases increases throughout the range of moderate and severe overweight for both men and women in all age groups.24
Overweight is defined as an increase in body weight above a standard related to height. Obesity, on the other hand, is defined as an abnormally high percentage of body weight as fat. In North America the body mass index (BMI; weight in kilograms divided by the square of height in meters) is widely used to distinguish between obese and nonobese adults aged 18 to 65 years. In this population, the BMI is a reliable measure of adiposity because it correlates strongly with body weight while adjusting for height. BMI is strongly correlated with fat mass measured densitometrically and adjusted for height (r is approximately 0.9 for both men and women). The measurement of the BMI is easily performed, and it has greater reproducibility than other measures of adiposity such as skinfold thickness indices. Overweight is defined as a BMI of 25 to 29.9 and obesity as a BMI of 30 or greater. A BMI of 30 is about 13.5 kg overweight and is equivalent to a weight of 99.5 kg in a person whose height is 1.8 m and to a weight of 84 kg in a person whose height is 1.7 m.
One limitation of the BMI is that it cannot distinguish between increased weight caused by adiposity or fluid retention, although this should be evident clinically. In recent years, body circumference indices (e.g., waist circumference, waist:height circumference ratio, waist:hip circumference ratio) have been advocated because they can identify adults with a central (android) pattern of obesity, who are at higher risk of obesity-related health problems independent of the BMI. A number of studies have established that central obesity is strongly correlated with mortality and risk for developing cardiovascular disease, diabetes mellitus, breast cancer, and stroke.59, 60 A waist circumference to hip circumference ratio >0.9 in women and >1.0 in men is associated with a higher risk of morbidity and mortality than a more peripheral distribution of body fat (waist:hip ratio, <0.75 in women and <0.85 in men). In the future, it is likely that body circumference indices will complement the BMI measurement in the evaluation of the health risks in adults with obesity.53
The etiology of obesity is heterogeneous, with several factors having the potential to cause a positive energy balance over long periods. These factors include a high-fat diet, a low level of habitual physical activity, a low resting metabolic rate for a given body mass and body composition, a high respiratory quotient in the fasting state (i.e., a tendency to oxidize more carbohydrates than lipids under standardized conditions), and perhaps high insulin sensitivity. Contrary to common belief, there is no consistent evidence that the current epidemic of obesity is caused by an increase in caloric intake. In fact, dietary studies conducted in many developed countries suggest that for adults, the average caloric intake, particularly in the form of fats, is lower than in previous decades. On the other hand, it is quite obvious that technologic advances have caused a marked reduction in the average daily expenditure of energy. Thus, low energy expenditure appears to be the key determinant of the current epidemic of obesity. Interest in the pathophysiology of obesity has recently intensified with the discovery of leptin, the antiobesity hormone.67, 95, 109 Leptin is a 167-amino acid protein with a structure similar to that of cytokines. The hormone is produced predominantly in white adipose tissue. Leptin circulates in the plasma in a free form or bound to leptin-binding proteins. Leptin levels increase exponentially with increasing fat mass, and leptin production is higher in subcutaneous than in visceral fat depots. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate neuroendocrine function and energy intake and expenditure. Leptin suppresses appetite, increases energy expenditure, and increases glucose and fat metabolism. Most obese subjects have high circulating leptin levels, indicating that in most circumstances obesity is a leptin-resistant state.