Definition and etiology

Obesity has become an important public health problem in industrialized countries throughout the world. The body mass index (BMI = weight [in kg]/height² [in m²]) is the primary measurement used to categorize obese patients (Table 1). Excess body weight (EBW) is defined as the amount of weight present in excess of ideal body weight (IBW), as determined by Metropolitan Life Tables. In 1991, the National Institutes of Health defined morbid obesity as a BMI of 35 kg/m² or higher with severe, obesity-related comorbidity or a BMI of 40 kg/m² or higher without comorbidity.¹

The development of obesity involves the interactions between excessive intake, inefficient calorie use, reduced metabolic activity, a reduction in the thermogenic response to meals, and an abnormally high set point for body weight. Genetic, environmental, and psychosocial factors all contribute to this problem.

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Prevalence and risk factors

The prevalence of obesity in the United States has increased from 15% in 1980 to 32% in 2004.² The prevalence of extreme obesity (BMI > 40 kg/m²) is 2.8% in men and 6.9% in women. The prevalence of childhood and adolescent obesity has tripled since 1980 and, currently, 17% of U.S. children and adolescents are overweight. Obesity and morbid obesity affect women and minorities (particularly middle-aged black and Hispanic women) more than white males. However, in almost every age and ethnic group, the prevalence of overweight or obesity exceeds 50%.

Recent studies have also delineated the importance of childhood weight for influencing adulthood weight. Being overweight during older childhood is highly predictive of adult obesity, especially if a parent is also obese. Being overweight during the adolescent years is an even greater predictor of adult obesity. Obesity is now the second leading cause of preventable death after cigarette smoking, despite expenditures of over $45 billion annually on weight loss products.³

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Pathophysiology and natural history

Adipose tissue is primarily stored in the subcutaneous tissue and abdominal cavity. In general, females are more likely to deposit fat in the peripheral tissues and males tend to deposit fat in the abdominal compartment. As obesity develops, the size and number of fat cells increase. As fat cells grow, they release increasing amounts of cytokines (and lower amounts of adiponectin); these changes have deleterious effects on glucose and lipid metabolism and contribute to the proinflammatory state associated with obesity.

Obesity shortens the life span of those who suffer with it. The mortality rate of an individual with a BMI higher than 40 kg/m² is double that of a normal-weight individual.⁴ It is estimated that a man in his twenties, with a BMI higher than 45 kg/m² has a 22% reduction in life expectancy: 13 years.⁵ Most obesity-related deaths result from complications related to diabetes and cardiovascular disease. Worldwide, approximately 2.5 million deaths occur annually because of obesity-related comorbidities.

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Signs, symptoms, and related diseases

There are more than 30 comorbid conditions associated with severe obesity. Insulin resistance and diabetes mellitus occur in 15% to 25% of obese patients. Increased abdominal fat raises the intra-abdominal pressure and contributes to gastroesophageal reflux, stress urinary incontinence, venous stasis disease, and abdominal hernia in obese patients. Fatty deposits in the liver can progress to nonalcoholic steatohepatitis (NASH) and ultimately to liver failure. Excess weight causes joint and back stress that can lead to debilitating joint disease. The low-grade inflammatory state associated with morbid obesity has been implicated in the development of vascular and coronary artery disease and the hypercoagulable state seen in these patients. Obese patients have impaired pulmonary function, particularly decreased functional residual capacity, and frequently suffer from asthma, obstructive sleep apnea, and obesity hypoventilation syndrome (pickwickian syndrome). Other comorbidities include hypertension, dyslipidemia, asthma, and sex hormone dysfunction. Obesity is associated with an increased incidence of uterine, breast, ovarian, prostate, and colon cancer and of skin infections, urinary tract infections, migraine headaches, depression, and pseudotumor cerebri.

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Diagnosis and evaluation of comorbidities

The diagnosis of morbid obesity is established by determining the patient's BMI and the presence of any significant comorbid conditions. A thorough history, physical examination, and focused testing will uncover previously undiagnosed comorbidities in up to two thirds of obese patients.

Visceral, or central, adiposity is more metabolically active than peripheral fat and is associated with type 2 diabetes, dyslipidemia (elevated triglyceride and reduced high-density lipoprotein [HDL] levels), high blood pressure, and increased risk for cardiovascular atherosclerotic disease. The waist-to-hip ratio helps to identify patients with excess visceral adiposity. Women with a waist-to-hip ratio of more than 0.8 and men with a ratio of more than 1.0 are considered to have excess central adiposity that confers risk for developing the metabolic syndrome. The diagnostic criteria for the metabolic syndrome are shown in Table 2.

The pretreatment evaluation performed at the Cleveland Clinic is consistent with published guidelines.⁶ Because obese persons are at higher risk for cardiovascular disease, a baseline electrocardiogram should be performed. Cardiology evaluation is carried out when there is evidence of cardiac disease based on clinical symptoms or electrocardiographic findings. Chest radiography and baseline laboratory testing, including a complete blood count, chemistry panel, liver function tests, thyroid function tests, and a lipid profile, should be performed as well.

Obstructive sleep apnea frequently goes unrecognized in this patient population until a thorough history prompts further evaluation. Patients with symptoms of loud snoring, daytime hypersomnolence, or a neck circumference of 43 cm or more should undergo polysomnography and, if positive, be treated with nasal continuous positive airway pressure. Asthma and obesity hypoventilation syndrome (chronic hypoxemia, hypercarbia, pulmonary hypertension, and polycythemia) are also severe pulmonary complications of obesity and should be evaluated by a pulmonologist.

Dietary counseling and psychological testing are required for patients being referred for bariatric surgery.

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Summary

• Severe obesity can adversely affect every organ system.
• Detailed evaluation of symptoms can uncover serious comorbidities.
• Diabetes and cardiovascular disease are common in obese patients.
• Central obesity is associated with the presence of the metabolic syndrome.

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Treatment

Lifestyle Modifications

According to the clinical guidelines published by the American College of Physicians, all patients with a BMI of 30 kg/m² or higher should be counseled intensively on lifestyle and behavioral modifications, such as appropriate diet and exercise.^7,8 An algorithm by the American College of Physicians for medically managing obesity is shown in Figure 1.⁸ The patient's goals for weight loss should be individually determined and may encompass other related parameters, such as decreasing blood pressure or fasting blood glucose levels. When establishing realistic weight loss goals, it is important to realize that modest weight loss (10%-15%) of baseline weight is sufficient to result in health benefits.^9,10

General diet guidelines for achieving and maintaining a healthy weight include eating balanced, nutritious foods to avoid vitamin deficiencies. Avoiding foods high in fat and simple sugars should be emphasized. In addition, eating about 50% to 55% of calories from complex carbohydrates and educating patients regarding portion sizes and caloric content of foods is recommended by several national scientific organizations, such as the American Dietetics Association and American Diabetes Association. Referral to a registered dietitian helps patients initiate and adhere to these dietary guidelines.

Every physician should include an exercise regimen as part of a comprehensive lifestyle modification plan. Moderate exercise has been shown to decrease blood pressure, increase HDL and reduce triglyceride levels, and is predictive of maintenance of weight loss and delaying onset of type 2 diabetes.¹¹ General exercise recommendations include 20 to 30 minutes of moderate exercise 5 to 7 days a week, and up to 60 minutes a day most days of the week for maintenance of weight and 90 minutes a day for achieving weight loss.

Medical Options

Pharmacologic therapy can be offered to obese patients who have failed to achieve their weight loss goals through lifestyle modification alone or have significant comorbidities. Before initiating therapy, patients must understand the drug's side effects, the lack of long-term safety data, and the temporary nature of the weight loss achieved with medications. Table 3 lists the medications reviewed in the 2005 American College of Physician clinical practice guideline for obesity management.⁷

The choice of agent depends on the side effect profile of each agent and the patient tolerance of those side effects. The amount of extra weight loss attributable to weight loss medications is modest (<5 kg at 1 year). However, even modest weight loss, as seen with medical management, can slow the progression of diabetes and positively influence cardiovascular risk factors There is no evidence that modest weight loss affects mortality.

The optimal duration of treatment with obesity medications has not yet been determined. Data from randomized controlled trials have examined only up to 12 months of therapy; thus, more long-term clinical trials need to be performed. There are no long-term data on whether these drugs decrease morbidity or mortality from obesity-related conditions.

Surgical Options

Indications

Patients with a BMI higher than 35 kg/m² with obesity-related comorbidities and those with a BMI higher than 40 kg/m² with or without comorbidities are eligible for bariatric surgery (Box 1).¹

Patients must have attempted medical weight loss programs and should be highly motivated to change their lifestyle after surgery. The NIH guidelines of 1991 have recommended age limits between 18 and 60 years. At that time, there was insufficient evidence to make recommendations about surgery for patients at the extremes of age. Although advanced age has been a predictor of increased mortality after bariatric surgery,^12,13 there is some evidence (case series) that supports bariatric surgery in carefully selected adolescents and older patients.

Contraindications

Patients who cannot tolerate general anesthesia because of cardiac, pulmonary, or hepatic insufficiency are not candidates for surgery. Additionally, patients must be able to understand the consequences of the surgery and comply with the extensive preoperative evaluation and postoperative lifestyle changes, diet, vitamin supplementation, and follow-up program. Patients who have ongoing substance abuse issues or unstable psychiatric illness are poor candidates for bariatric surgery.

Follow-up

Bariatric surgery patients require lifetime follow-up.¹ Early postoperative visits focus on complications and the dramatic changes in dietary habits. Later follow-up visits focus on psychological support, nutritional assessment and vitamin supplementation, and adherence to exercise programs. Patients who present with new onset abdominal pain, vomiting, or gastroesophageal reflux months to years after bariatric surgery should be referred to their bariatric surgeon. These symptoms may be secondary to an anastomotic ulcer or stricture or an intermittent bowel obstruction after Roux-en-Y gastric bypass (RYGB). After laparoscopic adjustable gastric banding (LAGB), new onset of gastroesophageal reflux or dysphagia may suggest gastric prolapse through the band. These patients require prompt evaluation and treatment for these conditions.

Procedures

Roux-en-Y Gastric Bypass

RYGB combines a restrictive and a malabsorptive procedure and is the most common bariatric procedure performed in the United States (80%). Most RYGB procedures are now performed laparoscopically, which results in faster recovery and fewer pulmonary and wound complications compared with open surgery. A small, 15- to 30-mL gastric pouch is created to restrict food intake, and a Roux-en-Y anastomosis bypasses the duodenum and proximal jejunum and provides a malabsorptive component. The risks and benefits associated with RYGB are shown in Figure 2. RYGB results in superior weight loss when compared with restrictive procedures with excellent long-term reduction in EWL (50% at 14 years) comorbidity resolution.

Laparoscopic Adjustable Gastric Banding

The LAGB is a restrictive procedure and the device (Lap-Band System, Inamed Health, Santa Barbara, Calif) was approved for use in the United States in 2001 after having excellent results in Europe and Australia. The silicone band, with an inflatable inner collar, is placed around the upper portion of the stomach to create a small gastric pouch. The band is connected to a port that is placed in the subcutaneous tissue of the abdominal wall. The inner diameter of the band can be adjusted by injecting saline through the port.

The adjustable nature of the LAGB is a major advantage that distinguishes it from vertical-banded gastroplasty. Band adjustments are made according to weight loss by injecting or removing saline from a subcutaneous port. Severe complications and mortality rates are lower for LAGB than RYGB, but LAGB typically results in less and more gradual weight loss. Common risks and benefits of LAGB are shown in Figure 3.

Vertical Banded Gastroplasty

Vertical banded gastroplasty (VBG) is a restrictive procedure that creates a small gastric pouch with a fixed banded outlet. However, 10-year follow-up data have shown that only 26% to 40% of patients maintain acceptable weight loss (>50% EWL) and one third of patients in these series returned to or exceeded their preoperative weight.¹⁴

Early complications after VBG are infrequent, but late complications have resulted in a 17% to 30% reoperation rate.¹⁵ Because of the poor long-term weight loss and high late complication rate, VBG has largely been abandoned. Patients with weight regain or severe gastroesophageal reflux disease (GERD) symptoms after VBG should be referred to a bariatric surgeon to discuss revision to RYGB.

Biliopancreatic Diversion

Biliopancreatic diversion is a malabsorptive procedure performed by less than 3% of bariatric surgeons in the United States. This procedure, and a modification called the duodenal switch, are designed to limit intestinal energy absorption to the length of the distal common channel. Although these procedures offer the best and most durable weight loss results of any bariatric procedure performed today, higher complication rates, nutritional deficiencies, and a higher mortality rate have limited their widespread use.

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Summary

• All obese patients (BMI > 30 kg/m²) should be counseled on lifestyle and behavioral modifications, such as appropriate diet and exercise.
• Pharmacologic therapy can be offered to obese patients who have failed to lose weight with diet and exercise.
• Bariatric surgery should be considered for morbidly obese patients who have failed medical weight loss programs (diet and exercise, with or without pharmacotherapy). Patients with a BMI higher than 40 kg/m², or higher than 35 kg/m² with obesity-related comorbidities, are candidates for bariatric surgery.

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Outcomes

In a meta-analysis of sibutramine in patients with a BMI of 25 kg/m² or higher, sibutramine was more effective than placebo in promoting weight loss in overweight and obese adults, with an average increased weight loss of 4.5 kg at 1 year compared with placebo.^16,17

In a meta-analysis of 29 studies of orlistat, the pooled mean weight loss for orlistat-treated patients was 2.59 kg at 6 months and 2.89 kg at 12 months. The average age of patients enrolled was 48 years and the average BMI was 36.7 kg/m².¹⁸

Other agents, such as phentermine, diethylpropion, and fluoxetine, result in a 3.0- to 3.6-kg weight loss after 1 year when used in combination with lifestyle interventions. There is a paucity of data regarding sertraline, bupropion, topiramate, and zonisamide on weight loss outcomes. Therefore, recommendations cannot be made until further studies have been completed.¹⁹

A randomized controlled trial evaluating use of the Lap-Band for mild to moderate obesity (BMI 30-35 kg/m²) has demonstrated significantly greater weight loss and comorbidity resolution in the surgical group compared with those enrolled in an aggressive medical weight loss program. After 2 years, EWL was 87% in the surgical group and 21% in the nonsurgical group. Metabolic syndrome resolved in 93% of surgical patients and in 47% of nonsurgical patients. A large, prospective, matched cohort study (Swedish Obese Subjects Study) demonstrated the durability of weight loss and comorbidity reduction 10 years after bariatric surgery.¹⁸ Another large, matched cohort study demonstrated a significant reduction in mortality (89% relative reduction compared with the medical group) 5 years after bariatric surgery.²⁰ A meta-analysis analyzing 22,094 patients in 136 studies found that for all bariatric procedures, the average excess weight loss was 61.2%. Biliopancreatic diversion or duodenal switch procedures had the highest overall EWL (70%), followed by gastroplasty (68%), gastric bypass (61%), and gastric banding (47%). Overall, diabetes improved or resolved in 86%, hyperlipidemia improved in 70%, hypertension improved or resolved in 78.5%, and obstructive sleep apnea improved or resolved in 83.6% of patients.²¹

The operative mortality rates for restrictive procedures, gastric bypass, and biliopancreatic diversion are 0.1%, 0.5%, and 1.1%, respectively.²¹ Mortality after bariatric surgery is primarily the result of pulmonary embolism and anastomotic leak. Early postoperative complications, particularly septic complications, are less common after restrictive procedures such as VBG and LAGB.

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Summary

• All obese patients (BMI > 30 kg/m²) should be counseled on lifestyle and behavioral modifications, such as appropriate diet and exercise.
• Pharmacologic therapy can be offered to obese patients who have failed to lose weight with diet and exercise.
• Bariatric surgery should be considered for morbidly obese patients who have failed medical weight loss programs (diet and exercise, with or without pharmacotherapy). Patients with a BMI higher than 40 kg/m², or higher than 35 kg/m² with obesity-related comorbidities, are candidates for bariatric surgery.

Suggested Readings

• Arterburn DE, Crane PK, Veenstra DL. The efficacy and safety of sibutramine for weight loss: A systematic review. Arch Intern Med. 2004, 164: 994-1003.
• Buchwald H, Avidor Y, Braunwald E, et al: Bariatric surgery: A systematic review and meta-analysis. JAMA. 2004, 292: 1724-1737.
• Christou NV, Sampalis JS, Liberman M, et al: Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg. 2004, 240: 416-423.
• Consensus Development Conference Panel. NIH conference. Gastrointestinal surgery for severe obesity. Ann Intern Med. 1991, 115: 956-961.
• Demaria EJ, Jamal MK. Surgical options for obesity. Gastroenterol Clin North Am. 2005, 34: 127-142.
• Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity. JAMA. 2005, 293: 1861-1867.
• Flum DR, Salem L, Elrod JA, et al: Early mortality among Medicare beneficiaries undergoing bariatric surgical procedures. JAMA. 2005, 294: 1903-1908.
• Fontaine KR, Redden DT, Wang C, et al: Years of life lost due to obesity. JAMA. 2003, 289: 187-193.
• Haddock CK, Poston WS, Dill PL, et al: Pharmacotherapy for obesity: A quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord. 2002, 26: 262-273.
• Harris MI, Flegal KM, Cowie CC, et al: Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care. 1998, 21: 518-524.
• Knowler WC, Barrett-Connor E, Fowler SE, et al: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002, 346: 393-403.
• Livingston EH, Huerta S, Arthur D, et al: Male gender is a predictor of morbidity and age a predictor of mortality for patients undergoing gastric bypass surgery. Ann Surg. 2002, 236: 576-582.
• McTigue KM, Harris R, Hemphill B, et al: Screening and interventions for obesity in adults: Summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2003, 139: 933-949.
• National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002, 106: 3143-3421.
• Ogden CL, Carroll MD, Curtin LR, et al: Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006, 295: 1549-1555.
• Pi-Sunyer FX. A review of long-term studies evaluating the efficacy of weight loss in ameliorating disorders associated with obesity. Clin Ther. 1996, 18: 1006-1035.
• Ramsey-Stewart G. Vertical banded gastroplasty for morbid obesity: Weight loss at short and long-term follow up. Aust N Z J Surg. 1995, 65: 4-7.
• Sauerland S, Angrisani L, Belachew M, et al: Obesity surgery: Evidence-based guidelines of the European Association for Endoscopic Surgery (EAES). Surg Endosc. 2005, 19: 200-221.
• Sjostrom L, Lindroos AK, Peltonen M, et al: Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004, 351: 2683-2693.
• Snow V, Barry P, Fitterman N, et al: Pharmacologic and surgical management of obesity in primary care: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2005, 142: 525-531.
• Wadden TA, Bartlett SJ, Foster GD, et al: Sertraline and relapse prevention training following treatment by very-low-calorie diet: A controlled clinical trial. Obes Res. 1995, 3: 549-557.
• Wolf AM, Colditz GA. The cost of obesity: The U.S. perspective. Pharmacoeconomics. 1994, 5: (Suppl 1): 34-37.