ESSENTIALS OF DIAGNOSIS
Decreased intake of energy or protein, increased nutrient losses, or increased nutrient requirements.
Kwashiorkor: caused by protein deficiency.
Marasmus: caused by combined protein and energy deficiency.
Protein loss correlates with weight loss: 35–40% total body weight loss is usually fatal.
Protein–energy malnutrition occurs as a result of a relative or absolute deficiency of energy and protein. It may be primary, due to inadequate food intake, or secondary, as a result of other illness. For most developing nations, primary protein–energy malnutrition remains among the most significant health problems. It occurs in two distinct syndromes. Kwashiorkor, caused by a deficiency of protein in the presence of adequate energy, is typically seen in weaning infants at the birth of a sibling in areas where foods containing protein are insufficient. Marasmus, caused by combined protein and energy deficiency, is seen where adequate quantities of food are simply not available.
In industrialized societies, protein–energy malnutrition is most often secondary to other diseases. Kwashiorkor-like secondary protein–energy malnutrition occurs primarily in association with hypermetabolic acute illnesses such as trauma, burns, and sepsis. Marasmus-like secondary protein–energy malnutrition typically results from chronic diseases such as chronic obstructive pulmonary disease (COPD), heart failure, cancer, or AIDS. These two syndromes are estimated to be present in at least 20% of hospitalized patients. A substantially greater number of patients have risk factors that could result in them. In both syndromes, protein–energy malnutrition is caused either by decreased intake of energy and protein or by increased nutrient losses or increased nutrient requirements from the underlying illness. For example, diminished energy intake may result from poor dentition or various gastrointestinal disorders. Increased nutrient losses result from malabsorption, diarrhea, and glycosuria. Increased nutrient requirements occur with fever, surgery, neoplasia, and burns.
Protein–energy malnutrition affects every organ system. The most obvious results are loss of body weight, adipose stores, and skeletal muscle mass. Weight losses of 5–10% are usually tolerated without loss of physiologic function; losses of 35–40% of body weight usually result in death. Loss of protein from skeletal muscle and internal organs is usually proportionate to weight loss. Protein mass is lost from the liver, gastrointestinal tract, kidneys, and heart.
As protein–energy malnutrition progresses, organ dysfunction develops. Hepatic synthesis of serum proteins decreases, and depressed levels of circulating proteins are observed. Cardiac output and contractility are decreased, and the electrocardiogram (ECG) may show decreased voltage and a rightward axis shift. Autopsies of patients who die with severe undernutrition show myofibrillar atrophy and interstitial edema of the heart.
Respiratory function is affected primarily by weakness and atrophy of the muscles of respiration. Vital capacity and tidal volume are depressed, and mucociliary clearance is abnormal. The gastrointestinal tract is affected by mucosal atrophy and loss of villi of small intestine, resulting in malabsorption. Intestinal disaccharidase deficiency and mild pancreatic insufficiency also occur.
Changes in immunologic function are among the most important changes seen in protein–calorie undernutrition. T lymphocyte number and function are depressed. Changes in B cell function are more variable. Impaired complement activity, granulocyte function, and anatomic barriers to infection are noted, and wound healing is poor.
Clinical manifestations of protein–energy malnutrition range from mild growth retardation and weight loss to a number of distinct clinical syndromes (eTable 29–8). In the developing world, children manifest marasmus and kwashiorkor. In industrialized nations, clinical manifestations of secondary protein–energy malnutrition are affected by the patient’s nutritional status prior to illness, illness resulting in the protein and energy deficiency, and degree of the deficiency.
Progressive wasting that begins with weight loss and proceeds to more severe cachexia typically develops in most patients with marasmus-like secondary protein–energy malnutrition. In the most severe form of this disorder, most body fat stores disappear and muscle mass decreases, most noticeably in the temporalis and interosseous muscles. Laboratory studies may be unremarkable—serum albumin, for example, may be normal or slightly decreased, rarely decreasing to less than 2.8 g/dL (28 g/L). In contrast, owing to its rapidity of onset, kwashiorkor-like secondary protein–energy malnutrition may develop in patients with normal subcutaneous fat and muscle mass or, if the patient is obese, even in patients with excess fat and muscle. The serum protein level, however, typically declines and the serum albumin is often less than 2.8 g/dL (28 g/L). Dependent edema, ascites, or anasarca may develop. As with primary protein–energy malnutrition, combinations of the marasmus-like and kwashiorkor-like syndromes can occur simultaneously, typically in patients with progressive chronic disease in whom a superimposed acute illness develops.
The treatment of severe protein–energy malnutrition is a slow process requiring great care. Initial efforts should be directed at correcting fluid and electrolyte abnormalities and infections. Of particular concern are depletion of potassium, magnesium, and calcium and acid–base abnormalities. The second phase of treatment is directed at repletion of protein, energy, and micronutrients. Treatment is started with modest quantities of protein and calories calculated based on the patient’s actual body weight. Adult patients are given 1 g/kg of protein and 30 kcal/kg of calories. Concomitant administration of vitamins and minerals is obligatory. Either the enteral or parenteral route can be used, although the former is preferable. Enteral fat and lactose are withheld initially. Patients with less severe protein–calorie undernutrition can be given calories and protein simultaneously with the correction of fluid and electrolyte abnormalities. Similar quantities of protein and calories are recommended for initial treatment.
Patients treated for protein–energy malnutrition require close follow-up. In adults, both calories and protein are advanced as tolerated, adults to 1.5 g/kg/day of protein and 40 kcal/kg/day of calories.
Patients who are re-fed too rapidly may develop a number of untoward clinical sequelae. During refeeding, circulating potassium, magnesium, phosphorus, and glucose move intracellularly and can result in low serum levels of each. The administration of water and sodium with carbohydrate refeeding can result in heart failure in persons with depressed cardiac function. Enteral refeeding can lead to malabsorption and diarrhea due to abnormalities in the gastrointestinal tract.
Refeeding edema is a benign condition to be differentiated from heart failure. Changes in renal sodium reabsorption and poor skin and blood vessel integrity result in the development of dependent edema without other signs of heart disease. Treatment includes reassurance, elevation of the dependent area, and modest sodium restriction. Diuretics are usually ineffective, may aggravate electrolyte deficiencies, and should not be used.
The prevention and early detection of protein–energy malnutrition in hospitalized patients require awareness of its risk factors and early symptoms and signs. Patients at risk require formal assessment of nutritional status and close observation of dietary intake, body weight, and nutritional requirements during the hospital stay.
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ESSENTIALS OF DIAGNOSIS
Excess adipose tissue; body mass index (BMI) greater than 30.
Upper body obesity (abdomen and flank) of greater health consequence than lower body obesity (buttocks and thighs).
Associated with health consequences, including diabetes mellitus, hypertension, and hyperlipidemia.
Obesity is one of the most common disorders in medical practice and among the most frustrating and difficult to manage. Little progress has been made in prevention or treatment, yet major changes have occurred in our understanding of its causes and its implications for health.
Obesity is defined as an excess of adipose tissue. Accurate quantification of body fat requires sophisticated techniques not usually available in clinical practice. Physical examination is usually sufficient to detect excess body fat. More quantitative evaluation is performed by calculating the BMI.
The BMI closely correlates with excess adipose tissue. It is calculated by dividing measured body weight in kilograms by the height in meters squared (eTable 29–9).
The National Institutes of Health (NIH) define a normal BMI as 18.5–24.9. Overweight is defined as BMI = 25–29.9. Class I obesity is 30–34.9, class II obesity is 35–39.9, and class III (extreme) obesity is BMI greater than 40. Factors other than total weight, however, are also important. Upper body obesity (excess fat around the waist and flank) is a greater health hazard than lower body obesity (fat in the thighs and buttocks). Obese patients with increased abdominal circumference (greater than 102 cm in men and 88 cm in women) or with high waist–hip ratios (greater than 1.0 in men and 0.85 in women) have a greater risk of diabetes mellitus, stroke, coronary artery disease, and early death than equally obese patients with lower ratios. Furthermore, visceral fat within the abdominal cavity is more hazardous to health than subcutaneous fat around the abdomen.
US survey data demonstrate that 68% of Americans are overweight and 33.8% are obese. Women in the United States are more apt to be obese than men, and African-American and Mexican-American women are more obese than whites. The poor are more obese than the rich regardless of race. Approximately 60% of individuals with obesity in the United States have the metabolic syndrome (including three or more of the following factors: elevated abdominal circumference, blood pressure, blood triglycerides, and fasting blood sugar, and low high-density lipoprotein [HDL] cholesterol).
Health Consequences of Obesity
Obesity is associated with significant increases in both morbidity and mortality. A great many disorders occur with greater frequency in obese people (eFigure 29–1). The most important and common of these are hypertension, type 2 diabetes mellitus, hyperlipidemia, coronary artery disease, degenerative joint disease, and psychosocial disability. Certain cancers (colon, ovary, and breast), thromboembolic disorders, digestive tract diseases (gallbladder disease, gastroesophageal reflux disease), and skin disorders are also more prevalent in the obese. Surgical and obstetric risks are greater. Obese patients also have a greater risk of pulmonary functional impairment including sleep apnea, endocrine abnormalities, proteinuria, and increased hemoglobin concentration. Patients with obesity have increased rates of major depression and binge eating disorder. Several studies have documented that obese individuals are also subject to various forms of social discrimination.
Role of obesity in the pathophysiology of disease. Some ways whereby obesity contributes to disease. Short arrows refer to a change in the indicated parameter, and long arrows indicate a consequence of that change. In some cases, evidence is epidemiologic; in others, it is experimental. (Modified and reproduced, with permission, from Bray GA. Pathophysiology of obesity. Am J Clin Nutr. 1992;55:488S.)
In young and middle-aged adults, mortality from all causes and mortality from cardiovascular disease increase in proportion to the degree of obesity. The relative risk associated with obesity, however, decreases with age, and weight is no longer a risk factor in adults over age 75 years. Analysis of data from the National Health and Nutrition Examination Survey (NHANES) has suggested that lesser amounts of excess weight (BMI between 25 and 29.9) may not be associated with excess mortality.
Obesity has been considered to be the direct result of a sedentary lifestyle plus chronic ingestion of excess calories. Yet, as much as 40–70% of obesity may be explained by genetic influences. Twin studies demonstrate substantial genetic influences on BMI with little influence from the childhood environment.
Five genes affecting control of appetite have been identified in mice. Mutations of each gene result in obesity, and each has a human homolog. One gene codes for a protein expressed by adipose tissue—leptin—and another for the leptin receptor in the brain. The other three genes affect brain pathways downstream from the leptin receptor. Numerous other candidate genes for human obesity have been identified. Only a small percentage of human obesity is thought to be due to single gene mutations. Most human obesity undoubtedly develops from the interactions of multiple genes, environmental factors, and behavior. The rapid increase in obesity in the last several decades clearly points to major roles for environmental and behavioral factors in its development. Cross-sectional studies associate obesity with changes in gut flora. It is unknown whether altered gut flora contributes to the development of obesity or whether obesity changes the gut flora.
Medical Evaluation of the Obese Patient
Historical information should be obtained about age at onset, recent weight changes, family history of obesity, occupational history, eating and exercise behavior, cigarette and alcohol use, previous weight loss experience, and psychosocial factors including assessment for depression and eating disorders. Particular attention should be directed at use of laxatives, diuretics, hormones, nutritional supplements, and over-the-counter medications.
Physical examination should assess the BMI, degree and distribution of body fat, overall nutritional status, and signs of secondary causes of obesity.
Less than 1% of obese patients have an identifiable secondary, nonpsychiatric, cause of obesity. Hypothyroidism and Cushing syndrome are important examples that can usually be diagnosed by physical examination in patients with unexplained recent weight gain. Such patients require further endocrinologic evaluation, including serum thyroid-stimulating hormone (TSH) determination and dexamethasone suppression testing (see Chapter 26).
All obese patients should be assessed for medical consequences of their obesity by screening for the metabolic syndrome. Blood pressure, waist circumference, fasting glucose, low-density lipoprotein (LDL) and HDL cholesterol, and triglycerides should be measured.
Using conventional dietary techniques, only 20% of patients will lose 20 lb and maintain the loss for over 2 years; only 5% maintain a 40-lb loss. Average weight loss is approximately 7% of baseline weight. Continued close provider–patient contact appears to be more important for success of treatment than the specific features of any given treatment regimen. Careful patient selection improves success rates and decreases frustration of both patients and therapists. Only sufficiently motivated patients should enter active treatment programs. Specific attempts to identify motivated patients—eg, requesting a 3-day diet record—are often useful.
Most successful programs employ a multidisciplinary approach to weight loss, with hypocaloric diets, behavior modification to change eating behavior, aerobic exercise, and social support. Emphasis must be on maintenance of weight loss.
Dietary instructions for most patients incorporate the same principles that apply to healthy people who are not obese. These instructions emphasize intake of a wide variety of predominantly “unprocessed” foods, with special attention to limiting foods that provide large amounts of calories without other nutrients, ie, fat, sucrose, and alcohol. There is no physiologic advantage to diets that restrict carbohydrates, advocate relatively larger amounts of protein or fats, or recommend ingestion of foods one at a time. Diets that are restricted in carbohydrates (such as the Atkins and South Beach diets), however, can be effective in achieving a lower total calorie intake. Several studies have demonstrated that low-carbohydrate diets can be used safely and effectively for weight loss without adverse effects on lipids or other metabolic parameters. Meal replacement diets can also be used effectively and safely to achieve weight loss.
Long-term changes in eating behavior are required to maintain weight loss. Although formal behavior modification programs are available to which patients can be referred, the clinician caring for obese patients can teach a number of useful behavioral techniques. The most important technique is to emphasize planning and record keeping. Patients can be taught to plan menus and exercise sessions and to record their actual behavior. Record keeping not only aids in behavioral change, but also helps the provider to make specific suggestions for problem solving. Patients can be taught to recognize “eating cues” (emotional, situational, etc) and how to avoid or control them. Regular self-monitoring of weight is also associated with improved long-term weight maintenance.
Exercise offers a number of advantages to patients trying to lose weight and keep it off. Aerobic exercise directly increases the daily energy expenditure and is particularly useful for long-term weight maintenance. Exercise will also preserve lean body mass and partially prevent the decrease in basal energy expenditure (BEE) seen with semistarvation. Compared to no treatment, exercise alone results in small amounts of weight loss. Exercise plus diet results in slightly greater weight loss than diet alone. A greater intensity of exercise is associated with a greater amount of weight loss. Up to 1 hour of moderate exercise per day is associated with long-term weight maintenance in individuals who have successfully lost weight. Social support is essential for a successful weight loss program. Continued close contact with clinicians and involvement of the family and peer group are useful techniques for reinforcing behavioral change and preventing social isolation.
Patients with severe obesity may require more aggressive treatment regimens. Very-low-calorie diets (typically 800–1000 kcal/day) result in rapid weight loss and marked initial improvement in obesity-related metabolic complications. Patients are commonly maintained on such programs for 4–6 months. Patients who adhere to the program lose an average of 2 lb per week. Average maximum weight loss is approximately 15% of initial weight. Most programs use meal replacement diets to achieve the very-low-calorie intake. Long-term weight maintenance following meal replacement programs is less predictable and requires concurrent behavior modification, long-term use of low-calorie diets, careful self-monitoring, and regular exercise. Side effects such as fatigue, orthostatic hypotension, cold intolerance, and fluid and electrolyte disorders are observed in proportion to the degree of calorie reduction and require regular supervision by a clinician. Other less common complications include gout, gallbladder disease, and cardiac arrhythmias. Although weight loss is more rapidly achieved with very-low-calorie diets as compared with traditional diets, long-term outcomes are equivalent.
Medications for the treatment of obesity are available both over the counter and by prescription. Considerable controversy exists as to the appropriate use of medications for obesity. NIH clinical obesity guidelines state that obesity drugs may be used as part of a comprehensive weight loss program for patients with BMI greater than 30 or those with BMI greater than 27 with obesity-related risk factors. However, few data suggest that medications can improve long-term outcomes associated with obesity.
Several medications are approved by the US Food and Drug Administration (FDA) for treatment of obesity. Catecholaminergic medications (eg, phentermine, diethylpropion, benzphetamine, and phendimetrazine) are approved for short-term use only and have limited utility. Orlistat (120 mg orally up to three times daily with each fat-containing meal) is available by prescription for longer-term treatment of obesity. A nonprescription lower-dose formulation (60 mg) is available. Rather than in the central nervous system, orlistat works in the gastrointestinal tract to inhibit intestinal lipase, reducing fat absorption. Not unexpectedly, it may cause diarrhea, gas, and cramping and perhaps reduced absorption of fat-soluble vitamins. In randomized trials with up to 2 years of follow-up, orlistat resulted in 2–4 kg greater weight loss than placebo. A beneficial impact on long-term obesity-related clinical outcomes has not been established.
Four additional medications are approved for use in the United States. Lorcaserin, a selective serotonin receptor agonist given in a dose of 10 mg orally twice daily, is associated with modest weight loss, about 3% of initial weight more than placebo. Approximately twice as many patients (38% vs 16%) lose more than 5% of initial weight on lorcaserin compared to placebo. Post-marketing surveillance is focused on concerns about increased breast tumors in animal studies, valvular heart disease in patients receiving earlier drugs of this class, and psychiatric side effects.
The combination of phentermine hydrochloride and topiramate (3.75 mg/23 mg orally daily for 14 days, then 7.5 mg/46 mg orally daily, to a maximum dosage of 15 mg/92 mg orally daily) results in dose-dependent weight loss. In clinical trials, patients receiving the lowest dose lost 7.8% more weight than those receiving placebo; with the higher dose, 9.8% more weight was lost. Common side effects include mood changes, fatigue, and insomnia. Since the medications increase heart rate, a large clinical trial to assess cardiovascular risk is being conducted. The combination is also associated with increased birth defects and should not be used during pregnancy. Its distribution is restricted in the United States (telephone 1-888-998-4887 or visit www.QsymiaREMS.com).
The combination of naltrexone and bupropion hydrochloride (8 mg ER/90 mg ER, increasing from 1 tablet orally daily by 1 additional daily tablet each week to a maximum of 2 tablets twice daily) is also approved by the FDA for weight loss. Clinical trials demonstrated a 2–4% weight loss compared to placebo after 1 year. Concerns include an increased risk of suicidal thoughts and behaviors, other neuropsychiatric events, seizures, and elevation of blood pressure and heart rate. Other side effects include nausea and vomiting, diarrhea and constipation, headache, and dry mouth. A cardiovascular outcome trial to further assess safety is in progress.
Liraglutide (Saxenda), an injectable incretin (a glucagon-like peptide-1 receptor agonist), is FDA approved for obesity treatment in a dose of 0.6 mg subcutaneously daily, increasing by 0.6 mg daily each week to a maximum of 3 mg subcutaneously daily. Clinical trials demonstrated a 3.7–4.5% weight loss compared to placebo at 1 year. Concerns include thyroid tumors in animal studies, pancreatitis, gallbladder disease, renal impairment, increased heart rate, and suicidal thoughts. Common side effects include nausea and vomiting, diarrhea and constipation, and hypoglycemia. A cardiovascular outcomes trial is being conducted.
Sibutramine was removed from the market by the FDA due to an increase in cardiovascular events in participants in a large randomized trial. This finding emphasizes the need to study the long-term effects of all weight loss medications on important clinical outcomes.
Bariatric surgery is an increasingly prevalent treatment option for patients with severe obesity. In the United States, gastric operations are considered the procedures of choice. Most popular is the Roux-en-Y gastric bypass (RYGB). In most centers, the operation can be done laparoscopically. RYGB typically results in substantial amounts of weight loss—over 30% of initial body weight in some studies. Complications occur in up to 40% of persons undergoing RYGB surgery and include peritonitis due to anastomotic leak; abdominal wall hernias; staple line disruption; gallstones; neuropathy; marginal ulcers; stomal stenosis; wound infections; thromboembolic disease; gastrointestinal symptoms; and nutritional deficiencies, including iron, vitamin B12, folate, calcium, and vitamin D. Operative mortality rates within 30 days are nil to 1% in low-risk populations but have been reported to be substantially higher in Medicare beneficiaries. One-year mortality rates have been reported as high as 7.5% in men with Medicare. Surgical volume (number of cases performed by the surgeon or hospital) has been demonstrated to be an important predictor of outcome.
Another operation is gastric banding. Gastric banding results in less dramatic weight loss than RYGB and has fewer short-term complications. Frequent follow-up, however, is required to adjust the gastric band. Longer-term follow-up has shown a 39% rate of major complications and a 60% rate of re-operation.
A third operation, sleeve gastrectomy, is gaining in popularity. With this procedure, approximately three-quarters of the stomach is resected, but the gastrointestinal tract is otherwise left intact. Weight loss results are somewhat less than RYGB but greater than gastric banding.
NIH consensus panel recommendations are to limit obesity surgery to patients with BMIs over 40, or over 35 if obesity-related comorbidities are present. The procedure is cost-effective for patients with severe obesity and most third-party payers cover the procedure in selected patients. A large Swedish study suggested that bariatric surgery is associated with a significant reduction in deaths at 11-year follow-up. The number needed to treat to prevent one death in 11 years was 77 operations. A US Veterans Administration study, however, did not show a mortality benefit.
Patients with BMI over 40 (or over 35 with obesity-related morbidities) who are interested in considering weight loss surgery.
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