Pathophysiology

Obesity involves both genetic and environmental factors. A segment of the population is genetically predisposed to obesity. Another segment of the population succumbs to adverse environmental conditions, such as fast food, sedentary jobs, and few opportunities to exercise. These individuals phenotypically express obesity.

Taking in more calories than are expended causes obesity. Overweight individuals tend to eat too many grams of fat and to consume too many calories. Although decreasing fat intake is important in reducing cardiovascular risk factors and lowering cholesterol, it is calories that really count with weight gain.

An individual’s energy expenditure must be closely examined. This is divided into three categories. First, resting energy expenditure is what the body consumes when just resting; this is about 60% of energy used in a day and depends on the amount of lean body mass and the individual’s age. Resting energy goes down with age and up with lean body mass. A person who has more muscle will have higher resting energy expenditure. It is very difficult to change this level to any significant degree. However, it does determine most of the energy that a person burns.

The second category of energy expenditure is the exercise or activity energy expenditure. This is about 30% of the energy burned and is highly variable. For example, a person who is relatively sedentary but who wiggles and fidgets burns about 600 more calories a day than the sedentary bradykinetic individual. Given this basic principle, patients who wish to lose weight should be more physically active.

The third category of energy expenditure comes from the thermic effect of food and is responsible for about 10% of energy expenditure. In obese individuals, small decreases occur in their thermic-effect-of-food rates, but these do not explain the obese state.

Adipose tissue in the body is used primarily to store energy in the form of triglycerides. During periods when food is not eaten, the body draws from the adipose tissue reservoir to find what is needed to help the individual survive. When the individual eats too much, the adipose tissue reservoir is overfilled. The store of triglycerides remains available to be broken down into fatty acids for use as energy. Considerable interest has been expressed in pursuits undertaken to enhance understanding of whether obese individuals are more efficient at storing triglycerides than lean people. It has been observed that an obese person who takes in 100 g of fat might be more likely to deposit that as adipose tissue, whereas a lean person might oxidize it and burn it off as heat.

When obesity is discussed at the cellular level, two factors must be considered: (1) how many fat cells the individual has, and (2) to what extent these fat cells are filled with fat. To answer these questions, it is important for one to understand that fat storage consists of two components: (1) the fat cells and (2) the stromal vascular or supporting connecting tissue. Fat cells start out as preadipocytes. These are fibroblast-like cells that do not respond to insulin, and they do not store fat. They are small, spindle-like cells that are found within the fat cell; they divide and can turn into fat cells with excessive stimulation of nutrients. These fat cells also can enlarge and make huge fat cells. There is a limit to how stretched these fat storage cells can become. After fat cells reach a certain level, they recruit additional preadipocytes to make more fat cells.

When the number of fat cells an individual has is determined, it can be seen that there are two critical times in life when many preadipocytes are made, and thus the person will develop a larger pool of fat cells for the body to use. The first time is at age 2, and the second is at puberty. An individual who becomes obese at 2 or at puberty has a bigger supply of precursor cells and thus may be more resistant to long-term weight loss. It is not correct to say that at puberty people have all the fat cells they will ever have, and that they will die with that number. People can accumulate fat cells throughout life if they give in to the environmental stimulus, which is overeating. Some metabolic diseases also contribute to the increased development of fat cells.

The reason why it is very difficult to lose weight, once an individual has formed extra fat cells, is that fat cells do not divide once they are differentiated, but they also do not die. In a process called programmed cell death, or apoptosis, cells get rid of excess cells. However, adipocytes, as a rule, do not go through apoptosis and die; they are around for life. Obesity must be prevented because once the individual has accumulated fat, it is very difficult to lose. Even if fat cells contain no fat, they remain prepared and are waiting to take up more triglycerides.

Obesity and adipose tissue mass are tightly regulated. Patients complain, “I just get so hungry, I start eating again, and then I gain weight back.” If individuals have a certain mass of adipose tissue, the body does whatever it can to defend that mass. As soon as patients start to reduce adipose tissue through diet and exercise, the body thinks it is starving, so it makes these individuals hungry. Many physiologic mechanisms kick in. Neuropeptides in the brain and enzymes in the lining of the stomach help to accomplish this. They stimulate the body to say it is hungry and to eat. All of these factor interactions in brain, environment, and adipose tissue work to try to restore fat mass to its previous level.

Disease Process

Obesity is an excess of body fat relative to lean body mass. Overweight is defined as body mass index (BMI) of 25 to 29.9 kg/m². Obesity is defined as BMI of 30 kg/m² or greater, according to the Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, published by the National Heart, Lung, and Blood Institute (NHLBI) in June 1998. These guidelines provide basic information underlying the diagnosis and management of obesity and should be consulted by all clinicians. The relationships between physical activity, diet, genetics, and other factors make weight reduction a complex physiologic process. Even for those individuals trying to lose weight, hunger-inducing hormones such as ghrelin remained at an altered level 1 year after patients lost weight due to dieting. This is why psychologic understanding and approaches are so important. Simply reframing one’s relationship with food is essential. The medical world attempts to explain obesity based on this complex physiology and may ignore the psychologic aspects of care. These biologic changes may explain why maintaining weight loss is so difficult.

Obesity is increasing in prevalence, both in this country and throughout the world, in all segments of the population. The prevalence of obesity increases with age and is often associated with a recent pregnancy. In the United States, obesity is more prevalent in some minority groups and in patients with lower income and less education.

The economic costs associated with people who are overweight or obese are tremendous. The total cost attributable to obesity was over $99 billion in 1995. One half of these costs were direct medical costs resulting from diseases attributed to obesity. Indirect costs represent lost productivity due to obesity and are similar to those associated with smoking. Because obesity is associated with the development of other chronic diseases such as diabetes, coronary heart disease, and arthritis, additional indirect costs associated with obesity increase dramatically. Thus costs are both individual and societal.

Assessment

The most useful estimate of body fat is the BMI. The BMI is a powerful indicator of health risk that should be included in the comprehensive evaluation of any patient. Currently many researchers suggest waist size is an even better predictor of health than BMI. Both of these assessment measures will be briefly discussed.

When patients are considered for a weight reduction program, one should assess their BMI, weight, waist circumference, overall risk status, and motivation to lose weight.

The BMI is a number that is derived by dividing the weight in kilograms by the height in meters squared. The easiest way for most individuals to do the calculation is to multiply 704.5 by the patient’s weight in pounds. Divide that number by the patient’s height in inches multiplied by itself. Conversion charts are easily available.

Normal BMI is considered to be 19 to 24.9 kg/m². By way of reference, the average fashion model has a BMI of about 16.5. Tiger Woods has a BMI of 21.

Persons with a BMI of 20 to 25 have the lowest mortality. For the most part, increasing BMI is associated with increasing mortality. If BMI is less than 25, the health risk is minimal. Patients with BMI above 27 are in the moderate range; with BMI above 40, it is more likely that they will develop diabetes or some other obesity-related condition. Obese geriatric patients have less upper and lower body function. The incidence of obesity does not change, but functional status changes in the geriatric population.

Although several classifications and definitions for degrees of obesity are accepted, the most widely accepted classifications are those from the World Health Organization (WHO), based on BMI. The WHO designations include the following:

In individuals who are overweight, where the fat is located is also an important consideration. Waist circumference is an independent predictor of risk factors and morbidity and is correlated with abdominal fat content. Men at high risk have a waist greater than 102 cm (40 in). Women at high risk have a waist greater than 88 cm (35 in). The Nurses’ Health Study has documented that women whose waist measurement is 38 inches or more have 3 times the risk of heart disease as do women whose waists measure 28 inches or less. Women who are apple-shaped and who have a high waist-to-hip ratio are at greater risk for heart disease than are pear-shaped women, whose weight is concentrated in their hips and thighs. A large waist correlates with the metabolic syndrome. Circumferences of 49 inches in men and 35 inches in women indicate a markedly increased potential risk requiring urgent therapeutic intervention.

Some authorities advocate a definition of obesity based on percentage body fat. For men, a percentage of body fat greater than 25% defines obesity, with 21% to 25% being borderline. For women, over 33% defines obesity, with 31% to 33% being borderline.

The body fat percentage can be indirectly estimated by using the Deurenberg equation, as follows: body fat percentage = 1.2(BMI) + 0.23(age) – 10.8(sex) – 5.4, with age being in years and sex being designated as 1 for males and 0 for females. This equation has a standard error of 4% and accounts for approximately 80% of the variation in body fat.

The metabolic syndrome has been identified as an important risk factor in obese patients for diabetes and cardiovascular disease. In this process, fat cells release substances such as free fatty acids, complement D and cytokines (which promote inflammation), prothrombic agents, and angiotensinogen. Free fatty acids increase insulin resistance, raising insulin levels and leading to increased sodium reabsorption. Elevated sodium levels are associated with higher blood pressure. Insulin resistance may result in elevated blood sugar levels and diabetes mellitus, and free fatty acids and increased lipids raise the risk of CAD. Diagnostically, metabolic syndrome must consist of three or more of the following:

A comprehensive definition of metabolic syndrome outlined by Kushner (2007) includes:

To measure waist circumference, locate top of right iliac crest. Place a measuring tape in a horizontal plane around abdomen at level of iliac crest. Before reading tape measure, ensure that tape is snug but does not compress the skin and is parallel to floor. Measurement is made at the end of a normal expiration.

Some US adults of non-Asian origin (eg, white, black, Hispanic) with marginally increased waist circumference (eg, 94 -101 cm [37 -39 inches] in men and 80 -87 cm [31 -34 inches] in women) may have strong genetic contribution to insulin resistance and should benefit from changes in lifestyle habits, similar to men with categorical increases in waist circumference. Lower waist circumference cutpoint (eg, ≥90 cm [35 inches] in men and ≥80 cm [31 inches] in women) appears to be appropriate for Asian Amercans.

Fibrates and nicotinic acid are the most commonly used drugs for elevated TG and reduced HDL-C. Patients taking one of these drugs are presumed to have high TG and low HDL.

Evaluation of overall patient risk requires consideration of all conditions that might be caused by obesity or overweight. These include cardiovascular risk factors, CAD, atherosclerosis, DM, sleep apnea, osteoarthritis, gallstones, physical inactivity, and high levels of serum triglycerides. Their presence increases the importance of weight reduction for that patient.

The clinician also must evaluate the patient’s reasons and motivation for weight loss, previous weight loss attempts, understanding of the problem, physical activity, diet, and financial constraints. Patient motivation is essential to weight loss success.