Obesity Treatment Guidelines
Obesity is the state of excess body fat stores, which should be distinguished from overweight (i.e., excess body weight relative to a person’s height).
- The etiology of obesity is usually unknown, but it is likely multifactorial and related to varying contributions from genetic, environmental, and physiologic factors.
- Genetic factors appear to be the primary determinants of obesity in some individuals, whereas environmental factors are more important in others. The specific gene that codes for obesity is unknown; there is probably more than one gene.
- Environmental factors include reduced physical activity or work; abundant and readily available food supply; increased fat intake; increased consumption of refined simple sugars; and decreased ingestion of vegetables, fruits, and complex carbohydrates.
- Excess caloric intake is a prerequisite to weight gain and obesity, but whether the primary consideration is total calorie intake or macronutrient composition is debatable.
- Many neurotransmitters, receptors, and peptides stimulate or decrease food intake in humans and animals (Table 57-1). An understanding of the relationships among these factors is still evolving.
- Activity is thought to play a role in obesity, but studies designed to test the benefit of increased physical activity yield inconsistent results.
- Weight gain can be caused by medical conditions (e.g., hypothyroidism, Cushing’s syndrome, hypothalamic lesion) or genetic syndromes (e.g., Prader-Willi syndrome), but these are unusual to rare causes of obesity.
PHYSIOLOGY AND COMORBIDITIES
- The degree of obesity is determined by the net balance of energy ingested relative to energy expended over time. The single largest determinant of energy expenditure is metabolic rate, which is expressed as resting energy expenditure (REE) or basal metabolic rate (BMR). The two terms are frequently used interchangeably because they differ by less than 10%.
- The major types of adipose tissue are (1) white adipose tissue, which manufactures, stores, and releases lipid; and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Obesity research includes evaluation of the activity of adrenergic receptors and their effect on adipose tissue with respect to energy storage and expenditure or thermogenesis.
- Obesity, especially excessive central adiposity, is associated with serious health risks and increased mortality. Hypertension, hyperlipidemia, insulin resistance, and glucose intolerance are known cardiac risk factors that cluster in obese individuals.
CLINICAL PRESENTATION AND DIAGNOSIS
- Excess body fat can be determined by skinfold thickness, body density using underwater body weight, bioelectrical impedance and conductivity, dual-energy x-ray absorptiometry (DEXA), computed axial tomography (CT) scan, and magnetic resonance imaging (MRI). Unfortunately, many of these methods are too expensive and time consuming for routine use.
- Body mass index (BMI) and waist circumference (WC) are recognized, acceptable markers of excess body fat, which independently predict disease risk.
- BMI is calculated as weight (kg) divided by the square of the height (m2.
- WC, the most practical method of characterizing central adiposity, is the narrowest circumference between the last rib and top of the iliac crest.
The goal of therapy should be reasonable and should consider initial body weight, patient motivation and desire, comorbidities, and patient age. If, for example, the primary goal is improved blood glucose, blood cholesterol, or hypertension, then the endpoint should be target levels of glycosylated hemoglobin, low-density lipoprotein cholesterol, or blood pressure; weight loss goals may be as little as 5%. If the primary goal is relief of osteoarthritis or sleep apnea, then weight loss of 10% or 20% may be more appropriate.
- Successful obesity treatment plans incorporate diet, exercise, behavior modification with or without pharmacologic therapy, and/or surgery.
- The primary aim of behavior modification is to help patients choose lifestyles conducive to safe and sustained weight loss. Behavioral therapy is based on principles of human learning, which use stimulus control and reinforcement to substitute desirable for learned, undesirable behavior.
- Many diets exist to aid weight loss. Regardless of the program, energy consumption must be less than energy expenditure. Highly restrictive diets often yield rapid short-term, but disappointing long-term, results.
- Surgery, which reduces the stomach volume or absorptive surface of the alimentary tract, remains the most effective intervention for obesity. Although modern techniques are safer than older procedures and have an operative mortality of 1%, there are still many potential complications. Therefore, surgery should be reserved for those with BMI greater than 35 or 40 kg/m2.
- The debate regarding the role of pharmacotherapy remains heated, fueled by the need to treat a growing epidemic and by the fallout from the removal of agents from the market. Reasons for withdrawal were cardiac valvular insufficiency and structural abnormalities for fenfluramine, potential cardiac valve problems for dexfenfluramine, and hemorrhagic stroke for phenylpropanolamine. Mazindol was also removed from the market.
- The National Task Force on the Prevention and Treatment of Obesity concluded that short-term use of anorectic agents is difficult to justify because of the predictable weight regain that occurs upon discontinuation. Long-term use may have a role for patients who have no contraindications, but further study is needed before widespread, routine use is implemented.
- Orlistat induces weight loss by lowering dietary fat absorption and improves lipid profiles, glucose control, and other metabolic markers. Soft stools, abdominal pain or colic, flatulence, fecal urgency, and/or incontinence occur in 80% of individuals, are mild to moderate in severity, and improve after 1 to 2 months of therapy. Orlistat interferes with the absorption of fat-soluble vitamins and cyclosporine.
- Sibutramine is more effective than placebo, but patients tended to regain weight after 6 months of treatment. Dry mouth, anorexia, insomnia, constipation, increased appetite, dizziness, and nausea occur 2 to 3 times more often than with placebo. Sibutramine should not be used in patients with coronary artery disease, stroke, congestive heart failure, arrhythmias, or monoamine oxidase inhibitor (MAOI) use.
- Phentermine (30 mg in the morning or 8 mg before meals) has less powerful stimulant activity and lower abuse potential than amphetamines and was an effective adjunct in placebo-controlled studies. Adverse effects (e.g., increased blood pressure, palpitations, arrhythmias, mydriasis, altered insulin or oral hypoglycemic requirements) and interactions with MAO inhibitors have implications for patient selection.
- Diethylpropion (25 mg before meals or 75 mg of extended-release formulation every morning) is more effective than placebo in achieving short-term weight loss. Diethylpropion is one of the safest noradrenergic appetite suppressants and can be used in patients with mild to moderate hypertension or angina, but it should not be used in patients with severe hypertension or significant cardiovascular disease.
- Amphetamines should generally be avoided because of their powerful stimulant and addictive potential.
- Ephedrine (20 mg with or without caffeine 200 mg, up to 3 times daily) had better appetite-suppressive and thermogenic activity than placebo in trials lasting up to 6 months. The most common side effects are tremor, agitation, nervousness, increased sweating, and insomnia. Palpitations and tachycardia have also been reported.
- Serotonergic agents lack the central stimulant effects and abuse potential associated with noradrenergic compounds, but serotonergic agents can alter sleep patterns and change affect. Patients receiving fluoxetine (60 mg daily) had an initial weight loss of 2 to 4 kg in placebo-controlled trials, but there were no differences between groups over periods of up to 1 year. Similar findings have been noted with sertraline (200 mg daily).
- Peptides (e.g., leptin, neuropeptide Y, galanin) are being investigated because exogenous manipulation may provide future therapeutic approaches to the management of obesity.
- Herbal, natural, and food-supplement products are often used to promote weight loss (Table 57-4). The Food and Drug Administration (FDA) does not strictly regulate these products, so the ingredients may be inactive and present in variable concentrations. In contrast with popular belief, these products are not inherently safer than prescription drugs. For example, more than 800 reports of serious adverse events (e.g., seizures, stroke, and death) were attributed to ephedrine alkaloids, which led the FDA to exclude them from dietary supplements.
EVALUATION OF THERAPEUTIC OUTCOMES
- Specific weight goals that are consistent with medical needs and patient desire should be established. Loss of 5% to 30% of initial weight at a rate of 1 pound per week is reasonable.
- Evaluation requires careful clinical, biochemical, and, if necessary, psychological evaluation. Progress should be assessed in a health care setting once or twice monthly for the first 1 to 2 months, then monthly. Each encounter should document weight, WC, BMI, blood pressure, medical history, and tolerability of drug therapy.
- Diabetic patients require more intense medical monitoring and self-monitoring of blood glucose. Some anorectic agents have direct effects that improve glucose tolerance.
- Patients with hyperlipidemia or hypertension should be monitored to assess the effects of weight loss on appropriate endpoints.