Portal de Periódicos da CAPES

Evaluation and Treatment of Obesity

2006; Elsevier BV; Volume: 4; Issue: 6 Linguagem: Inglês

10.1016/j.cgh.2006.03.008

1542-7714

Lawrence A. Szarka, Amy E. Foxx–Orenstein,

Bariatric Surgery and Outcomes

A 38-year-old woman with type 2 diabetes, hyperlipidemia, well-controlled hypertension, diarrhea-predominant irritable bowel syndrome, and sleep apnea presents to discuss medical treatments for obesity. She has been overweight since childhood and has dieted since her teenage years using fad or commercial weight-loss programs. Maximal weight loss achieved was 9% of her body weight at 6 months on 3 occasions, but she was unable to keep the weight off beyond 1 year. She works as a travel agent out of her home and is married with 2 teenage children. Her medications include atorvastatin, hydrochlorothiazide, diltiazem, and oral hypoglycemic agents, and she uses continuous positive airway pressure inconsistently. She is not involved in an exercise program. On physical examination, her body mass index (BMI) is 37 kg/m2, blood pressure is 142/64 mm Hg, and heart rate is 62 beats per minute. The physical examination is otherwise normal. Her total cholesterol level is 210 mg/dL, low-density lipoprotein cholesterol level is 127 mg/dL, fasting blood glucose level is 148 mg/dL, and hemoglobin A1C level 9.2%. What is the role of lifestyle modification and pharmacotherapy in the treatment of her obesity? What would be the role of bariatric surgery in this patient? Obesity is defined as an increase in body weight beyond skeletal or physical requirement as the result of excessive accumulation of fat in the body. Guidelines for the classification of weight status based on BMI (weight in kilograms divided by the square of the height in meters) define overweight as a body mass index of 25.0–29.9 kg/m2, class I obesity as 30.0–34.9 kg/m2, class II obesity as 35.0–39.9 kg/m2, and class III obesity as 40 kg/m2 or higher. The United States and large parts of the rest of the world are experiencing an epidemic of overweight and obesity. The prevalence of obesity in the United States has increased from 14.5% to 30.5% between 1976–1980 and 1999–2000. Currently, close to 65% of the United States’ adult population is overweight or obese. Obesity is known to cause, aggravate, or be a risk factor for many diseases (Table 1). In addition, obesity is associated with impaired quality of life and negatively impacts on self-reported physical functioning, general health perception, vitality, and bodily pain. In the workplace, obesity is associated with increased sick leave, absenteeism, and disability claims. It is estimated that obesity leads to medical costs of $90 billion and more than 110,000 excess deaths annually. The obesity epidemic has triggered personal injury litigation against food and food service companies and discussions on limiting advertising for food, taxing food consumption, and subsidizing physical activity.Table 1Medical Complications of ObesityCardiovascular Vascular disease Hypertension Atrial fibrillationEndocrine Type 2 diabetes DyslipidemiaGastroenterologic CholelithiasisPulmonary Obesity hypoventilation Obstructive sleep apneaRheumatologic Gout OsteoarthritisUrologic Erectile dysfunction Kidney stones Urinary stress incontinenceMiscellaneous Cataracts Idiopathic intracranial hypertension Polycystic ovary disease Cancer Cervical Colon Esophageal Gallbladder Kidney Pancreatic Prostate Ureteral Open table in a new tab The causes of obesity in individuals and the epidemic of obesity in affluent societies are incompletely understood. The possibility that defects in metabolism are important in obesity has been investigated carefully. Total energy expenditure is composed of approximately 70% resting energy expenditure, 10% thermic effect of food (energy expenditure associated with digestion and absorption), and 20% activity thermogenesis, which includes exercise (smallest component of total energy expenditure in developed countries—near zero for most people) and nonexercise activity, such as talking, walking, finger tapping, fidgeting, and so forth. Studies comparing obese and normal-weight individuals have not shown any significant differences in either total energy expenditure or any of its components. Although diet-induced weight loss decreases resting energy and activity thermogenesis, this is a transient phenomenon that does not persist with maintenance of a lower weight. Patients may complain of inability to lose weight despite eating very little, but there is typically an underestimation of food intake, a well-documented phenomenon. Appetite and eating are under complex neurohumoral regulation. There are a variety of neuropeptides in the gut including cholecystokinin, glucagon-like peptide-1, glucose-dependent insulinotropic peptide, oxyntomodulin, bombesin, peptide YY 3–36, and pancreatic polypeptide that may act in multiple ways to achieve satiation through local (eg, gastric emptying delay and ileal braking) and central effects. Leptin is produced mainly by adipose tissues and acts centrally as another anorexigenic factor. Ghrelin is an important orexigenic (appetite-stimulating) peptide produced by the stomach that increases during fasting and cachexia. Input from the vagal afferents and circulating factors are integrated by the hypothalamus and brain stem. There are, in turn, central neurotransmitters that are characterized as orexigenic or anorexigenic. In general, monoamines, such as serotonin and catecholamines, and pro-opiomelanocortin and its metabolites suppress appetite. Other neurotransmitters such as neuropeptide Y, agouti-related peptide, melanin-stimulating hormone, and orexin serve to increase appetite. Isolated mutations in genes for leptin and other neuropeptides and their receptors have been described as rare causes of obesity in human beings and have helped the understanding of the molecular mechanisms of appetite and gave provided targets for future pharmacologic treatment. Although the genetic component of human obesity is understood better now, the worldwide epidemic of obesity during the past 20 years is explained best by behavioral and environmental changes that have affected individual energy intake–energy expenditure balance. The calories provided by the US food supply have increased from 3300 kcal per capita in 1970 to 3800 kcal per capita in the late 1990s. Portion sizes and access to prepared food both inside and outside the home have increased, including the phenomena of super-sized meals, unlimited buffet-style dining, and drive-through fast food. Physical activity has decreased as television viewing and automobile ownership have increased, as have other sedentary activities such as playing video games and surfing the Internet. Overall, it seems that technologic advances have made the household, yard, and workplace more productive with less physical energy expenditure. Although there is no evidence that intentional weight loss itself reduces mortality, the rationale for treating obesity is that intentional weight loss is known to decrease many of the complications associated with obesity. These include complications related to cardiovascular disease, type 2 diabetes, dyslipidemia, hypertension, respiratory disease, reproductive dysfunction, and measures of quality of life. The current available treatments are dietary therapy, physical activity, behavioral therapy, pharmacotherapy, and surgery. Dietary treatment (a conscious decision to eat less) is the most important component of management because it is easier to attain the negative energy balance needed for weight loss by decreasing caloric intake than by increasing physical activity. Treatment guidelines from the National Institutes of Health recommend that patients with class I obesity decrease their energy intake to create a 500-kcal/day energy deficit that will result in an approximately 1-lb weight loss per week and a 10% weight loss over 6 months. It is recommended that patients with class II or III obesity aim for an energy deficit of 500- to 1000-kcal/day, which will produce an approximately 1- to 2-lb weight loss per week and a 10% weight loss at 6 months. Recommendations based on energy deficits require technology to measure resting energy expenditure that is not readily available. Therefore, it is recommended that patients simply follow a low-calorie diet (defined as containing 800–1500 kcal/day). The efficacy of low-calorie diets has been studied in more than 30 randomized clinical trials that showed an approximately 8% weight loss after 16 to 26 weeks of dieting. Very low caloric diets ( 27 with weight-related comorbidity) who have not lost the recommended 1 lb/wk after 6 months of diet, exercise, and behavioral therapy may be prescribed pharmacotherapy. Effective treatment requires long-term therapy because patients who respond to pharmacotherapy regain weight when the drug is stopped. Only sibutramine and orlistat are approved by the Food and Drug Administration for use beyond 3 months in the treatment of obesity. Sibutramine is an anorexiant that acts by inhibiting norepinephrine and serotonin reuptake in the brain. Orlistat does not suppress the appetite; it works by inhibiting pancreatic lipase to decrease fat absorption. Pharmacotherapy has a modest effect on weight loss, but it is more effective when combined with a comprehensive weight management approach. In two 1-year trials of sibutramine, between 40% and 57% of patients lost 5% or more and 13%–34% lost 10% or more of their body weight (compared with 9%–20% and 4%–7%, respectively, for placebo). The use of sibutramine alone was not as effective as sibutramine in conjunction with a comprehensive weight-loss program including biweekly behavioral therapy, exercise, and portion-controlled low-calorie diet (4.1% initial body weight compared with 16.5%, respectively). Side effects of sibutramine include dose-related increase of blood pressure and heart rate (average increase of 2–4 mm Hg systolic pressure and 4–6 beats per minute), and mild dry mouth, headache, constipation, and insomnia. Patients should be evaluated every month for the first 3 months and then every 3 months after that to monitor weight, blood pressure, and heart rate. The usual starting dose of sibutramine is 10 mg/day, and in patients who have not responded at 1 month the dose can be adjusted upward, if tolerated, in 5-mg increments, up to a maximum of 30 mg/day. Orlistat is prescribed at a dose of 120 mg 3 times daily with meals. Seven randomized 1-year trials showed 35%–55% of patients lost 5% or more of their body weight, and 16%–25% of subjects lost 10% or more of their body weight (compared with 16%–27% and 4%–12%, respectively, for placebo). The side effects of orlistat are related to inhibition of intestinal fat absorption. About 4% of subjects on orlistat had to be withdrawn from studies because of gastrointestinal side effects. There is also a concern about malabsorption of fat-soluble vitamins with long-term use. Therefore, it is recommended that all patients treated with orlistat also take a daily multivitamin at a different time from the orlistat dose. Longer-term (>2 y) data on the efficacy of pharmacotherapy are lacking. If patients regain a substantial amount of their weight while on pharmacotherapy, the medication should be stopped. Gastrointestinal surgery is an effective treatment indicated for patients with class III obesity or class II obesity with related comorbidity who are unable to lose weight or maintain weight loss with conventional therapy. Two types of surgeries have proven to be safe and effective: those that restrict stomach volume, banded gastroplasty (Figure 1), and those that restrict gastric volume and cause maldigestion, Roux-en-Y gastric bypass (Figure 2) and biliopancreatic diversion (Figure 3). The Roux-en-Y gastric bypass procedure accounts for the majority of bariatric procedures currently performed. In randomized trials, the Roux-en-Y gastric bypass procedure was more effective than vertical banded gastroplasty with 67% of patients losing 50% of their excess weight at 1 year, compared with 48% in the vertical banded gastroplasty group. Biliopancreatic diversion (BPD) is a malabsorptive weight-loss procedure that involves removing part of the stomach to form a larger pouch than the prior 2 surgeries (200 compared with 15 mL). The portion of intestine that is bypassed or skipped is much longer than the Roux-en-Y and therefore fewer calories can be absorbed. This surgery is associated consistently with effective weight loss (≥70% of excess weight) but the degree of malabsorption can result in vitamin deficiencies. A variant of BPD is the BPD with a duodenal switch, which differs from the BPD in the portion of stomach removed, preservation of the pylorus, and long length of the roux limb. It has been advocated for those with superobesity (BMI >50 kg/m2). The average weight loss for the Roux-en-Y bypass procedure is maintained for up to 14 years, whereas 10-year outcomes for vertical banded gastroplasty show that only about one fourth of patients maintain the 50% excess weight loss. Thirty-day mortality rates for bariatric surgery from large series generally range from .3% to 2.0%. Perioperative mortality is related mainly to anastomotic leak and the increased risk for pulmonary embolism in extremely obese patients. Subsequent morbidity and the need for rehospitalization in the following years (which occurs in 20% of patients within 1 year of the surgery) is related to complications of the surgery itself including gallstone formation, incisional hernia, stomal stenosis, marginal ulcers, staple-line disruption, certain nutritional deficiencies, and dumping syndrome. Patients should use a daily vitamin and mineral supplement and are advised to use appropriate contraception to avoid pregnancy during the first postoperative year and until weight has stabilized. Levels of iron, magnesium, calcium, folate, and vitamins B12, A, D, and E should be monitored every 6 months in BPD patients. In all others, if patients are compliant with taking a daily multivitamin and clinically stable, the vitamin D level is checked annually.Figure 2Roux-en-Y gastric bypass.View Large Image Figure ViewerDownload (PPT)Figure 3Biliopancreatic diversion.View Large Image Figure ViewerDownload (PPT) Ghrelin is a circulating peptide produced principally in the stomach, which stimulates growth hormone secretion, increases appetite, induces a positive energy balance, and produces weight gain. Its orexigenic properties suggest it may be beneficial as a modulator of long-term body weight regulation. It is not entirely clear how ghrelin increases food intake, if it regulates intestinal motor function, or how its unique situation as a circulating appetite stimulant may be used in the treatment of weight-related disorders. Other enteric peptides such as glucagon-like peptide-1, oxyntomodulin, peptide YY, and pancreatic polypeptide are anorexigenic, serving to decrease appetite and promote satiety, although the physiologic roles of these compounds are diverse. Whether these peptides, limited by a short half-life, and stability can serve as long-term modulators of appetite and weight control remains to be seen. Liposuction, a surgical treatment that removes adipose by aspiration after the injection of physiologic saline, is used to remove and contour subcutaneous fat. Unlike weight loss by dieting (reduced nutrient intake) or bariatric surgery, which cause a negative nitrogen balance, liposuction does not appear to be associated with improvement in insulin sensitivity or reduction in risk factors for coronary heart disease. Rimonabant, a cannabinoid-1–receptor antagonist is a new investigational agent in the treatment of obesity. The endocannabinoid system is postulated to regulate food intake, energy balance, and lipid and glucose metabolism through peripheral and central mechanisms. In large, placebo-controlled trials, rimonabant showed efficacy in weight loss and improving metabolic parameters. Future studies will determine safety, efficacy, and mechanisms of activity on obesity and metabolic and gastrointestinal functions. Guidelines published by the National Institutes of Health and by the American Gastroenterological Association recommend that the patient should be assessed for obesity by the BMI. Additional assessment of cardiovascular disease risk factor status should be made based on waist circumference, family history, and laboratory test results. If the patient has a BMI greater than 30 or a waist circumference greater than 35 inches for women or greater than 40 inches for men, and 2 additional risk factors, then weight loss should be recommended to achieve a goal weight loss of 10% of baseline weight over 6 months using a low-calorie diet, increased physical activity, and behavior therapy. If lifestyle therapies are unsuccessful after 6 months, then pharmacotherapy can be considered in addition to ongoing diet, exercise, and behavioral therapy for patients with a BMI greater than 27 and weight-related comorbidity or a BMI greater than 30 without comorbidity. If the addition of pharmacotherapy is unsuccessful and the patient has a BMI greater than 35 and comorbidity, or a BMI greater than 40 without comorbidity, then Roux-en-Y gastric bypass surgery can be considered (Figure 4). Had this patient failed 3 meaningful attempts at weight loss using a lifestyle modification approach, proceeding to pharmacotherapy would have been an option. Because this patient has not been on a regimen of lifestyle modification previously, she should be advised to decrease her caloric intake to 800–1000 kcal/day, aiming for weight loss of 1–2 lb/wk or 10% over 6 months. The patient should be instructed in a low-calorie diet, encouraged to exercise regularly, and become involved in a behavior-modification program to maximize results. If at 6 months she has failed to achieve a 10% loss of her initial body weight, sibutramine 10 mg should be started. She requires monitoring of her weight, blood pressure, heart rate, and other symptoms every month while on the weight-loss program. If she has not decreased her weight at 1 month, increasing the dose of sibutramine by 5-mg increments each month to a maximum of 30 mg would be appropriate. Sibutramine, rather than Orlistat, is chosen for this patient because of her history of diarrhea. At 6 months, if she is able to reach her goal, she should continue with sibutramine and the comprehensive program for the long term. If by 6 months she is not able to meet her goals, because she has class II obesity with comorbidities, a Roux-en-Y gastric bypass should be recommended because this has been shown to be more effective than vertical banded gastroplasty in several trials. This patient started on sibutramine 10 mg/day with lifestyle modifications and a modest exercise program but experienced only a .5-lb weight loss by 1 month. The dose of sibutramine then was increased to 15 mg/day, the calorie deficit was increased from 500 to 1000 kcal/day, and her exercise program was increased. By 6 months she had lost 12% of her initial body weight and 14.2% by 1 year. At 2 years her weight remained stable on maintenance treatment with a daily intake of 1200–1500 kcal, behavioral modification, evaluation by a health care worker every 3 months, and a regular exercise program. At 2 years her total cholesterol level had decreased to 184 mg/dL, low-density lipoprotein cholesterol to 97 mg/dL, fasting blood glucose level to 118 mg/dL, and hemoglobin A1C level to 7.2%.