Obesity
1. Define the terms “overweight” and “obesity.”
Overweight and obesity are defined as degrees of excess weight that are associated with increases in morbidity and mortality. In 1998, the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) published guidelines on the diagnosis and treatment of overweight and obesity. The expert panel advocated using specific body mass index (BMI) cutoff points to diagnose both conditions. The BMI is calculated by dividing a person’s weight in kilograms by his or her height in meters squared. A BMI (kg/m2) of 25 or less is defined as normal; 25 to 29.9, as overweight; 30 to 34.9, as mild obesity; 35 to 39.9, as moderate obesity; and greater than 40, as severe or morbid obesity.
2. Does fat distribution affect the assessment of risk in an overweight or obese patient?
Yes. Accumulation of excessive adipose tissue in a central—or upper—body distribution (android or male pattern) is associated with a greater risk of adverse metabolic health consequences than lower-body obesity (gynoid or female pattern). Abdominal adiposity is an independent predictor of risk for diabetes, hypertension, dyslipidemia, and coronary artery disease. The absolute amount of intraabdominal or visceral fat is most closely linked to these adverse health risks.
3. Explain the role of waist circumference in risk stratification.
For this reason, the waist circumference is the favored measure for risk stratification on the basis of fat distribution. Men with a waist circumference greater than 40 inches (> 102 cm) and women whose waist circumference is greater than 35 inches (> 88 cm) have increased risk. Waist circumference is most useful for risk stratification in people with a BMI between 25 and 30 kg/m2. In this intermediate-risk group, those with increased waist circumference should undertake greater efforts directed at preventing further weight gain, whereas those with a smaller waist circumference can be reassured that their weight does not pose major health hazards.
4. How is waist circumference measured?
Waist circumference should be measured with a tape measure parallel to the floor at the level of the iliac crest at the end of a relaxed expiration.
5. What adverse health consequences are associated with obesity?
Obesity is clearly associated with diabetes, hypertension, hyperlipidemia, coronary artery disease, degenerative arthritis, gallbladder disease, and cancer of the endometrium, breast, prostate, and colon. It has also been associated with urinary incontinence, gastroesophageal reflux, infertility, sleep apnea, and congestive heart failure. The incidence of these conditions rises steadily as body weight increases (Figs. 7-1 and 7-2). Risks increase with even modest weight gain. Health risks are magnified with advancing age and a positive family history of obesity-related diseases.
6. Summarize the economic consequences of obesity.
The total direct and indirect health care costs associated with obesity were estimated to be $147 billion in 2008. In 2006, annual medical spending was $1429 (42%) greater for obese people than for normal-weight people. Almost 90% of the increase in costs attributable to the care of obese people is due to the rise in the prevalence of obesity. In addition, the NIH estimated that Americans pay $44 billion for weight loss products and services.
7. What are the psychological complications of obesity?
Situational depression and anxiety related to obesity are common. The obese person may suffer from discrimination, which contributes further to difficulty with poor self-image and social isolation. It may be difficult in some patients to determine whether depression is accelerating weight gain or whether weight gain is exacerbating an underlying depression, but treating both conditions may improve quality of life. Work by the Rudd Center and other groups has highlighted the bias that obese patients experience even from doctors who care for them. It is important for treating physicians to at least be aware of a tendency to blame obese patients for their condition and to compensate for this common bias as best they can if present.
Obesity has reached epidemic proportions in the United States. The National Health and Nutrition Examination Survey (NHANES) conducted by the federal government uses direct measures of height and weight in a representative sample of Americans to estimate the prevalence of obesity. The prevalence of obesity increased significantly during the 1980s and 1990s but has now leveled off. The latest data from the NHANES showed that in 2009 to 2010, 35.7% of adults in the United States had a BMI greater than 30 kg/m2. This rate of obesity has not changed significantly from those in 2003 through 2008. The prevalence of overweight (BMI > 25 kg/m2) was found to be 68.8%. The prevalence of severe obesity (BMI > 40 kg/m2) was 6.3% in the latest dataset. In children and adolescents aged 2 to 19 years, the prevalence of obesity was found to be 16.9%, not changed from 2007 to 2008 prevalences.
9. What caused the dramatic rise in the prevalence of obesity in the 1980s and 1990s?
The prevalence of obesity indeed rose over this short period; it seems that the primary culprit is a changing environment that promotes increased food intake and reduced physical activity. This statement should not be taken to mean, however, that body weight is not subject to physiologic regulation. The control of body weight is complex, with multiple interrelated systems controlling caloric intake, macronutrient content of the diet, energy expenditure, and fuel metabolism.
10. Describe the current model for obesity as a chronic disease.
Obesity is now viewed as a chronic, often progressive metabolic disease much like diabetes or hypertension. This view requires a conceptual shift from the previous widely held belief that obesity is simply a cosmetic or behavioral problem. Development of obesity requires a period of positive energy balance during which energy intake exceeds energy expenditure. Maintaining energy balance is one of the most important survival mechanisms of any organism. A sustained negative imbalance between energy intake and expenditure is potentially life-threatening within a relatively short time. To maintain energy balance, the organism must assess energy stores within the body; assess the nutrient content of the diet; determine whether the body is in negative energy or nutrient balance; and adjust hormone levels, energy expenditure, nutrient movement, and ingestive behavior in response to these assessments.
11. Do abnormal genes cause obesity?
Obesity is clearly more common in people who have family members who are also obese. Genetics appears to be responsible for 30% to 60% of the variance in weight in most populations. The problem of human obesity, however, involves an interaction between genetic susceptibility and environmental triggers. The genes that we possess to regulate body weight evolved somewhere between 200,000 and 1 million years ago, at which time the environmental factors controlling nutrient acquisition and habitual physical activity were dramatically different. A number of single gene defects have been identified that cause severe childhood obesity. These include mutations in the leptin gene, leptin receptor, the MC4R gene, brain-derived neurotrophic factor (BDNF), and SIM-1. However, these mutations are quite rare, explaining less than 8% of severe early-onset obesity. Genome-wide association studies have identified more than 20 genes that are associated with common forms of human obesity. The most common of these is the FTO gene. The allele of this gene that is associated with weight gain is present in 15% of humans. However, the weight gain associated with this high-risk allele is only 3 kg. Thus, common human obesity appears to be the result of alterations in a large number of genes, each having relatively small effects (polygenic).
Leptin is a hormone secreted exclusively by adipose tissue in direct proportion to fat mass. It was discovered in 1994. Leptin acts through receptors located on neurons in the arcuate nucleus of the hypothalamus and other brain regions to regulate both food intake and energy expenditure. Changes in leptin levels in the hypothalamus alter the production of a number of neuropeptides, including pro-opiomelanocortin (POMC) and Agouti-related peptide (AGRP).
13. Does leptin deficiency cause human obesity?
There are a handful of cases in which genetic deficiency of either leptin or its receptor has been found to cause severe early-onset obesity. Treating leptin-deficient humans with leptin results in dramatic weight loss. However, leptin levels are typically higher in obese than in lean humans in proportion to the former’s greater fat mass. Studies in which recombinant human leptin was administered to typical obese humans produced minimal weight loss. These findings suggest that common forms of human obesity are associated with leptin resistance, not leptin deficiency.
14. Explain how the melanocortin system is involved in weight regulation.
Alpha-melanocortin (alpha-melanocyte–stimulating hormone [α-MSH]) is one of the hormone products of the POMC gene. This neuropeptide acts in the hypothalamus on melanocortin receptors, particularly the MC4-R subtype, to regulate body weight. By stimulating the MC4-R, α-MSH inhibits food intake, whereas the natural antagonist, Agouti-related peptide (AGRP), which is also made in the hypothalamus, stimulates food intake. MC4-R agonists have been developed. Although these drugs decrease food intake and reduce body weight in obese rodents, they have not been found to be useful as single agents in obese humans. The failure of these drugs and others that work through hypothalamic regulatory pathways to produce significant weight loss in obese humans has raised questions about the role of these systems in common forms of human obesity.
Ghrelin is a hormone originally identified as a growth hormone–releasing hormone produced by the stomach and proximal small intestine that appears to regulate appetite. Ghrelin levels rise before meals and promptly drop following food intake. Self-reported hunger mirrors serum ghrelin levels. Twenty-four-hour ghrelin levels rise when people go on an energy-restricted diet and are dramatically reduced after gastric bypass surgery. Ghrelin has been described as a “hunger hormone” and is another possible target for weight loss drugs. The bioactive form of the hormone, acylated ghrelin, has a fatty acid attached to the parent hormone. Drugs that alter the production of acylated ghrelin are also being investigated.
16. Does a decrease in energy expenditure play a role in the development of obesity?
The development of obesity requires an imbalance between caloric intake and caloric expenditure. For fat mass to increase, there must be an imbalance between the amount of fat deposited and the amount of fat oxidized. One possibility is that people become obese because of a reduction in their energy expenditure. Despite the common idea that a “low metabolic rate” predisposes to obesity, there is little evidence that this is true.
17. What are the components of energy expenditure?
Basal metabolic rate (BMR): The amount of energy needed to maintain body homeostasis by maintaining body temperature, maintaining cardiopulmonary integrity, and maintaining electrolyte stability.
18. Explain the concept of energy balance.
When an individual is weight stable, total daily energy expenditure equals total daily energy intake. Total energy expenditure is linearly related to lean body mass. Studies that have used sophisticated methods for measuring energy expenditure have clearly shown that obese people consume more calories than lean people. The obese person who says that he or she eats only a small amount but is gaining weight may be telling the truth in the short term, but over longer periods, high caloric intakes are required to maintain the obese state. Although reduced levels of PAEE may predispose to obesity, BMR is not reduced in obese people. The central cause of obesity is the failure to couple energy intake to energy expenditure accurately over time.
19. Are there other factors involved in the increase in the prevalence of obesity?
Over the past 10 years, investigators have identified a range of novel environmental factors that may be related to the increase in obesity seen over the past 40 years. One area that has received a good deal of attention is reduced sleep time. It is clear that on average Americans are sleeping less than they did 50 years ago. Epidemiologic studies have shown that shortened sleep time is associated with obesity, and experimental studies have shown that sleep restriction is associated with insulin resistance, increased appetite, and a change in fat oxidation. Medication use is another factor that may be involved in promoting obesity. Widely used medications that promote weight gain include newer antipsychotic medications, sulfonylureas, insulin, thiazolidinediones, and progesterone-containing birth control medications. Other novel factors that are potentially involved include the aging of the population as well as increases in the number of ethnic minorities in the United States, the use of climate control systems in houses and public buildings (mice housed in thermoneutral environments weigh more than mice housed at lower temperatures), and environmental toxins (some studies suggest that adipose tissue increases in response to environmental toxins in an effort to sequester them).
20. What options are available for treating the obese patient?
