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Obesity


Epidemiology

It is estimated that three of five American adults are overweight or obese (> 100 million persons) and the cost of obesity in the United State is in excess of $100 billion annually. In the last 30 years, the prevalence of obesity has nearly doubled from 12.8% to 22.5% of the U.S. population. The prevalence of obesity is particularly high in many ethnic minority women (e.g., African American, Mexican American, Native American, Pacific Islander American, Puerto Rican, and Cuban American). Obesity, in fact, is second to tobacco use as a public health hazard, contributing to more than 300,000 premature deaths annually and is associated with a twofold increase in mortality. Obesity is also on the increase in young adults and children. In minority populations, up to 30% to 40% of the children and adolescents are overweight. The precise amount of body fat mass that causes medical complications depends on patient’s gender, body fat distribution, weight (fat) gain since early adulthood, level of fitness and genetic factors.

Definition

Obesity is defined as a complex multifactorial chronic disease that develops from an interaction of genotype and environment. The type of fat accumulated and the site where the fat is deposited has different health implications and require different approaches to management.

Body mass index

Table BODY MASS INDEX represents the relationship between weight and height. Body mass index is calculated as weight in kilograms divided by height in square meters or as weight in pounds multiplied by 704.5 and divided by height in square inches. The National Institutes of Health has issued guidelines for the classification of weight status by Body mass index that separates patients by risk: Those with a Body mass index of 25.0 to 29.9 kg/m2 are considered overweight; those with a Body mass index more than 30 kg/m2 are considered obese. Extreme obesity is defined as a Body mass index more than 40 kg/m2 and carries a much higher risk for morbidity and mortality. The optimal Body mass index to minimize the consequences of obesity-related diseases is probably in the range of 19 to 21 kg/m2 for women and 20 to 22 kg/m2 for men. It is reported that American adults, especially women, who weigh 15% less than their age-matched, normal-weight peers have a significant reduction in projected mortality. Additional factors such as fat distribution and recent weight gain also modify the risk within each Body mass index category. Persons with increased abdominal fat have increased risk for hypertension, ischemic heart disease, dyslipidemia, diabetes mellitus, and insulin resistance syndrome than those with increased gluteal and femoral fat.

Weight gain during adulthood is an additional risk factor for medical complications. Weight gain of 75 kg in body weight since the age of 18 to 20 years increases the relative risk for cholelithiasis, diabetes mellitus, hypertension, and ischemic heart disease.Waist circumference correlates adequately with abdominal fat distribution. Deposition of fat in the abdomen, particularly if it is out of proportion to fat distribution elsewhere in the body, represents a health risk for morbidity and mortality that is independent of being overweight or obese. Measuring waist circumference, best taken at the level of the umbilicus with the patient in the supine position, is a reasonable method for assessing a patient’s health risk and monitoring weight-reduction interventions.

Waist-to-hip ratio is another measurement that may be helpful in assessing the risk of morbidity and mortality in relation to excess weight. The waist circumference is measured at the level of the umbilicus with the patient in the supine position and the hip circumference should be measured at the maximal girth around the buttocks. The Waist-to-hip ratio is calculated as

Waist-to-hip ratio = Waist circumference (cm or in)/hip circumference (cm or in)

TABLE. WEIGHT-ASSOCIATED DISEASE RISK
Weight Class
Body Mass
Index (kg/m2)
Waist Circumference
Women >88 cm or 35 in.
Men >102 cm or 40 in.
Extreme obesity >40 Extremely high risk
Obesity II >35-39.9 Very high risk
Obesity I >30-34.9 High risk
Overweight >25-29.9 Increased risk
Normal 18-24.9 Increased risk
Underweight <18.5 Increased risk

A Waist-to-hip ratio of more than 0.95 for males and more than 0.80 for females is associated with an increased risk of morbidity and mortality.

Pathogenesis

Both genetic and environmental factors contribute to body size. Genetic background can explain up to 40% of the variance in body mass in humans. However, the marked increase in the prevalence of obesity in the last 20 years cannot be attributed to genetic change and may be caused by alterations in the environment.

Obesity originates from ingesting more energy and calories than is expended over a long period of time. The excess ingested calories are stored as fat. Even small, but persistent differences between energy intake and energy expenditure can lead to large increases in body fat. For example, ingestion of only 5% more calories than expended could result in the accumulation of about 5 kg of adipose tissue in one year. Ingestion of 7 kcal/day more than expended over 30 years can lead to an increase of 10 kg body weight, which is the average amount of weight gained by American adults from 25 to 55 years of age.

Technological advances have led to changes in lifestyle that favor a positive energy balance due to an increased availability and palatability of inexpensive energy-dense foods, decreased daily physical activity because of labor-saving devices, changes in job-work patterns, and accessibility to mechanical transportation. Persons with certain genetic backgrounds are particularly predisposed to weight gain when they are exposed to this «modern» lifestyle. For example, Pima Indians living in reservations in Arizona have a much greater prevalence of obesity and diabetes mellitus than their genetic counterparts who live in rural areas of Mexico.

The modern American diet of fast food and beverages are high in fat and calories and low in nutritional value. An estimated 60% to 90% of Americans are undernourished meaning that despite excessive caloric intake, they do not meet their daily recommended dietary allowances (RDAs) in one or more food groups. In addition to increased caloric intake, only about 9% of men and 3% of women exercise vigorously on a regular basis as part of their leisure time activities.

Medical complications associated with obesity. Obesity is a significant risk factor for many medical diseases, impaired quality of life and premature death.

In addition, obese individuals experience depression, frustration, insecurity, and other negative feelings because of the way society reacts to them and the way they feel about themselves.

Therapy

General principles.

Table PRINCIPLES OF WEIGHT REDUCTION AND MAINTENANCE lists the key principles involved in the therapy of obesity.

Americans spend in excess of $70 billion a year on commercial weight-loss products. Most persons lose weight on these diets, but unfortunately within 1 to 5 years the weight is gained back with extra pounds.

Obesity is a chronic illness and requires long-term management for long-term success. Behavior modification is necessary for long-term lifestyle changes. Dietary and nutritional education is also very important. Patients should be encouraged to lose weight in a systemic and modest way through increased insulin sensitivity, decreased blood pressure and blood lipid levels, and reduction of fatty infiltration of the liver.

TABLE. OBESITY-ASSOCIATED MEDICAL COMPLICATIONS
Cardiovascular Hypertension, congestive heart failure, pulmonary hypertension, coronary artery disease, arrhythmia, ischemic stroke, venous stasis, deep vein thrombosis, pulmonary embolism
Pulmonary Pulmonary hypertension, sleep apnea, obesity-hypoventilation syndrome
Gastrointestinal Ventral hernia, gastroesophageal reflux, gallstone, steatohepatitis
Musculoskeletal Osteoarthritis, low back problem, gout
Endocrine-metabolic Diabetes mellitus, insulin resistance, dyslipoproteinemia (hypertriglyceridemia, hypercholesterolemia)
Genitourinary Menstrual dysfunction, infertility, complication of pregnancy, urinary stress incontinence
Postoperative risk Deep vein thrombosis, pulmonary embolism, atelectasis, and pneumonia
Cancer Breast, uterus, prostate, colon, gallbladder, cervix
Psychiatric Social stigmatization, psychoemotional disorder

Caloric reduction needs to be individualized based on the individual’s age and comorbid risk factors. A useful formula for losing about a pound a week is as follows:

Current weight in pounds x 13 kcal – 500 kcal = daily caloric requirement

Reduction of fat intake is essential in a successful weight-reduction program. Many patients will do well by reducing their total dietary fat intake to 10% to 20% of their total caloric intake (about 20-30 g of total dietary fat daily). Most commercial weight loss programs limit caloric intake to 800 to 1,200 calories a day. When followed carefully, these programs will induce a weight loss of 0.5 to 2.0 lbs a week for up to 30 weeks.

Many «fad diets» have little merit. Some of these diets may be actually harmful. For example, avoiding carbohydrates will induce ketosis; excessively high protein intake may adversely affect the kidneys and accelerate calcium loss from bones thereby promoting or enhancing osteoporosis. In addition, reduced caloric intake may lead to micronutrient deficiencies that impair metabolic fitness.

The assistance of a dietitian is very important. The National Registry of Dietitians may be contacted for recommendations of a dietitian in patients’ living areas (telephone: 1-800-366-1655). Diet advice should include encouraging patients to eat three meals a day, avoid snacking between meals, avoid energy-dense and high-fat foods, and increase the intake of fruits and vegetables.

Physical activity is important for long-term weight management and improved health. Physical activity should be increased slowly over time. Studies suggest that about 80 minutes per day of moderate-intensity exercise (e.g., brisk walking or 35 minutes per day of vigorous activity such as fast bicycling or aerobic exercise) is needed for long-term weight maintenance after initial weight loss has been achieved. Physical activity does not necessarily have to be part of a structured exercise program. Increasing daily lifestyle activities is just as effective in maintaining weight loss as participating in an aerobic program exercise.

TABLE. PRINCIPLES OF WEIGHT REDUCTION AND MAINTENANCE
Long-term weight loss and management

Gradual and modest weight loss in increments

Nutrition education

Behavior modification

Physical activity

Pharmacotherapy

Surgery

Recent data indicate that weight-resistance training appears to be the most beneficial form of exercise for successful weight management. By improving the integrity of existing muscle or by developing muscle mass, this type of exercise increases overall metabolism and enhances the oxidation of fat as fuel. These effects make long-term weight control far more likely.

Very-low-calorie diets or protein-sparing diets are proven, safe alternatives to starvation for significant sustained and progressive weight loss. These diets deliver a total daily caloric intake of 400 to 800 calories. Successful and safe programs include a daily intake of 0.8 to 1.0 g of protein per kilogram of desirable body weight or about 70 to 100 grams of protein and at least 45 to 50 grams of carbohydrate to minimize nitrogen losses and ketosis, respectively. All Very-low-calorie diets require careful physician supervision and close patient monitoring. Generally, weight loss is rapid and progressive for several weeks to months. After about 6 months, weight loss slows and plateaus and further weight loss becomes difficult to achieve. Unfortunately, once the Very-low-calorie diet is discontinued, initial weight-loss maintenance is also difficult to sustain. Incorporation of regular exercise and lifestyle changes improve the likelihood of sustaining the weight loss. Intermittent use of Very-low-calorie diet products or meal substitutions along with restrained eating patterns offer considerable promise.

Pharmacotherapy

It is extremely difficult to achieve and sustain significant reductions in weight and body fat in obese patients without pharmacotherapy or Very-low-calorie diets. Pharmacotherapy can help selected patients maintain long-term weight loss, but it should not be considered a short-term treatment approach. Obesity is a chronic disease and patients who respond to drug therapy usually regain weight when the drug therapy is stopped. Also, the effectiveness of pharmacotherapy may diminish with time. It is of paramount importance that pharmacotherapy be coupled with dietary, lifestyle, and behavioral changes.

Sibutramine hydrochloride maleate (Meridia) is a relatively new drug that was approved by the U.S. Food and Drug Administration (FDA) for long-term use in 1997. It is a monoamine reuptake inhibitor that was initially developed as an antidepressant to prevent the reuptake of serotonin, dopamine, and norepinephrine; thus, it synergistically promotes enhanced satiety and a reduction in food intake. In most patients, it induces a dose-dependent reduction in weight. The drug is available in capsule form in once-daily doses of 5, 10, and 15 mg. In one study, at one year, 39% of patients randomized to sibutramine hydrochloride maleate (15 mg per day) lost 70% of their initial body weight compared to 9% of those randomized to receive placebo. Based on clinical trials, it appears to be safe. With long term use, parallel to the weight loss, successful reduction in obesity associated comorbid conditions has also been observed.

The most common side effects associated with sibutramine hydrochloride maleate therapy are dry mouth, headache, constipation, and insomnia. These were usually mild and transient. Small increases in systolic rate (1-3 mm Hg) and heart rate (4-5 beats per minute) occur in some patients. However, in a very small percentage of patients, greater increases in blood pressure and pulse may occur and reduction of dose or discontinuation of the drug may be necessary.

Orlistat (Xenical) was approved by the FDA in 1999 for control of obesity. Orlistat inhibits gastric and pancreatic lipases and impedes the hydrolysis of dietary triglycerides into fatty acids; consequently, a significant portion of dietary fat is not absorbed and passes undigested through the small intestine to the colon for elimination in stool. In clinical trials of Orlistat given in dosages of 120 mg three times daily (t.i.d.) with meals, at 1 year, 40% of the patients had lost more than 10% of their initial body weight compared with 20% of patients receiving placebo. Thus, Orlistat was noted to be effective in inducing weight loss and reducing abdominal adiposity regardless of meal composition. The drug does not ameliorate hunger or enhance satiety. The side effects include abdominal cramping, loose stools, and flatulence; however, with a high dietary fat intake, reducing fat intake to less than 60 g a day eliminates most of these gastrointestinal (gastrointestinal) side effects. A slight decrease in plasma concentration of fat-soluble vitamins A and D and B-carotene was observed, but their levels remained in the normal range. Orlistat is contraindicated in patients with chronic malabsorption or cholestasis.

Olestra is a fat substitute that consists of six to eight fatty acids esterified to a sucrose molecule. Olestra resembles fat (butter) in texture and taste, but it is not hydrolyzed by the lipolytic enzymes of the gastrointestinal tract and is excreted unchanged with stool. It is commercially used in the production of potato chips and is also marketed as a butter substitute; thus, the drug may help patients reduce their fat intake by satisfying the taste for butter or fat.

Surgery (bariatric surgery) is the most effective approach for achieving weight loss in extremely obese patients (Body mass index > 40 kg/m2) or patients with a Body mass index of 35 to 40 kg/m2 and obesity-related diseases who are unlikely to lose weight with nonsurgical therapy. Patients need to be well enough to have acceptable surgical risks and are able to comply with long-term follow-up treatment.

The most commonly used surgical techniques are the gastric restrictive and gastric bypass procedures. Gastric restrictive procedures include gastric stapling and vertical-banded gastroplasty and partition to the stomach into a small upper pouch of 15 to 30 mL that empties into the rest of the stomach through a narrow channel. The gastric bypass procedure, also known as a Roux-en-Y gastric bypass, limits food intake and induces dumping by creating a small (15-30 mL) pouch in the cardia that drains into a segment of jejunum that is brought up as a Roux-en-Y limb.

Gastric restrictive procedures usually cause less weight loss than gastric bypass procedures. Within the first 2 years after surgery, more than 60% of excess weight is lost after gastric bypass compared with 40% after vertical-banded gastroplasty. The perioperative mortality rate is less than 1% and the risk for postoperative complications (i.e., anastomotic leak, ulcers, or stenosis) is 10% for both procedures. Bypassing the duodenum can cause malabsorption of iron, calcium, folate, and vitamin B12, and dumping syndrome.

The biliopancreatic bypass or the duodenal switch is used in patients with a Body mass index of more than 40 kg/m2 and is designed to induce maldigestion and malabsorption. Seventy-five percent of the stomach is removed along the greater curvature leaving the pylorus intact. The gastric pouch empties into the proximal ileum brought up to the pouch. The remaining duodenojejunal segment is anastomosed to the distal ileum 50 cm proximal to the ileocecal valve. This procedure causes loss of more than 70% of excess weight. However, malabsorption of fat, iron, calcium, vitamin B12, and fat-soluble vitamins may lead to nutritional and metabolic problems.

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