Obesity: Dormant Volcano Waiting to Erupt
Obesity: Dormant Volcano Waiting to Erupt
Authors: Udaya Kabadi MD, Chief, Endocrine Section, VAMC, Des Moines, IA, Professor of Clinical Medicine, University of Iowa, Iowa City, IA; and Devendra Wadwekar, MD, Clinical Adjunct Assistant Professor of Medicine, University of Iowa, Iowa City, IA.
Peer Reviewer: Rita M. Anderson, MD, PhD, Clinical Instructor of Surgery, Wright State University School of Medicine, Dayton, OH.
Introduction
The incidence and prevalence of obesity in the United States has increased dramatically in the past few decades. According to the latest data from the Centers for Disease Control and Prevention (CDC), the prevalence of obesity in the United States in adults over the age of 20 stands at 33.3% for men and 35.3% for women.1 The age group of 40-59 years had the highest prevalence among both men and women.1 Furthermore, the prevalence in both adults and children is reaching epidemic proportions and has led to a prediction by CDC that the life expectancy in this country would start declining in the next 20 years.1,2 In fact, according to CDC, it has already fallen in a couple of states as reported recently in the news media.3
Definition
Obesity is defined as increased body fat, usually more than 40% of total body mass.2 Normal body fat is 15-20% of total body mass for men and 20-25% for women.2 However, obesity in children is defined as weight more than 95th percentile for age- and sex-matched controls.4 In clinical practice, overweight is defined as between 10-20% over ideal body weight, and the diagnosis of obesity is made when individual's body weight is more than 120% of ideal body weight.2 Ideal body weight is defined as the body weight with minimum morbidity and mortality for age, sex, and height as established by the actuary data from Metropolitan Life Insurance Company and is revised every 30 years.5,6 The presently used formula is based on the most recent table published in 1983 by Metropolitan Life.7 It calculates ideal body weight in a man as 106 lbs for the first 5 feet (ft) of height and then adding 6 lbs for each additional inch (in). In women, 100 lbs is the ideal body weight for a height of 5 ft, and 5 lbs are added for each additional inch (a 10% variance is allowed for a large or a small frame, respectively).
Types of Obesity
On a pathological level, two classifications are used. In one, obesity is divided into two main types: hyperplastic, which is increased fat cell number (calculated as total body fat divided by adipose cell size, usually over 84 x 109); and hypertrophic, which is increased fat content per cell (usually more than 84 microgram lipid/cell).8 Hypertrophic is the most common type in adults, whereas hyperplastic is characteristic obesity of juvenile onset. In another classification, obesity is divided once again into two types based on regional fat distribution, i.e., subcutaneous fat and visceral fat. Visceral fat is more resistant to insulin as compared to subcutaneous fat and, therefore, a better predictor of both mortality and morbidity.
Diagnosis
Several methods are used in the diagnosis of obesity. Some utilize various formulae using height and weight to determine generalized obesity, whereas other methods are used to determine regional fat distribution.
Body mass index (BMI) is calculated by dividing weight in kilograms (kg) by square of height in meters (m2). Normal BMI is defined as less than 25 kg/m2. Any person having BMI between 25 to 30 kg/m2 is considered to be overweight, whereas obesity is defined as BMI over 30 kg/m2, with greater than 40 kg/m2 being defined as morbid obesity.1,2,9
Broca's Index. Dr. P. P. Broca, a French surgeon, developed a formula in 1871, according to which ideal body weight (in kg) should equal height (in cm) – 100, with a variance of ± 15% for women or 10% for men, depending on the size of the body frame.10 He defined obesity as body weight above that range.
Skin fold thickness measurements are used to determine subcutaneous fat to estimate the degree of adiposity. Measurements of triceps skin fold (midway between the acromion and olecranon) greater than 23 mm in men and 30 mm in women is indicative of obesity.11 This method is more commonly used in children and adolescents.
Adipose tissue biopsy can be used to estimate fat cell population and fat cell size in an individual. It is the most reliable and accurate technique for determining the degree of obesity; however, it is rarely used because of its invasiveness.
Miscellaneous Methods. Some of the other methods include measurement of total body fat content by various techniques, such as measurement of total body potassium, total body water, body density determined by underwater imaging or DEXA, and estimation of distribution of fat-soluble gases. However, the need for extensive and expensive equipment renders these methods impractical in clinical practice and, therefore, they are rarely used. Finally, determination of visceral fat content is important because of its ability to predict cardiac and metabolic risks. Various methods, i.e., bone densitometry, ultrasound, computerized scan, or magnetic resonance imaging, may be used. However, because of cost involved with these techniques, they are not commonly used. Instead, determination of regional fat distribution is performed by measuring the waist and hip circumferences for visceral and subcutaneous adiposity, respectively. Waist circumference is measured with a tape measure around the bare abdomen just above the hip bone (anterior superior iliac spine), and measuring around the most outward point on the hip denotes the hip circumference.12 The tape must be snug, should not compress the skin, and should be parallel to the floor. Measurements are more accurate when done after exhalation of a normal breath. A waist circumference of more than 102 cm (40 in.) in men or more than 88 cm (35 in.) in women is indicative of visceral adiposity. Waist circumferences greater than 94 cm in men and greater than 80 cm in women, and waist-to-hip ratios greater than 0.90 in men and greater than 0.85 in women are the thresholds for significantly increased potential cardiac and metabolic risks.13-16 Circumferences of 102 cm in men and 88 cm in women indicate a markedly increased potential risk requiring prompt therapeutic intervention.13-16 Finally, these thresholds for waist-hip ratios vary with geographic regions of the world, with much lower measurements in Asian populationless than or equal to 90 cm for men and 80 cm for womenbeing considered safe.17
Etiology
Although the causes of obesity can be broadly divided into five major categories (see Table 1), it is multi-factorial in etiology. Each individual may have a combination of different factors, discussed below, leading to abnormal weight gain.
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Genetic. Familial Trends. Studies of twins have clearly established a genetic basis of obesity.18-19 However, other factors also appear to play a role since twins raised apart have a lower incidence compared to twins raised together.20-21 Several studies have documented a 50-80% chance of developing obesity in children of two obese parents, and the probability declines to 10% if both parents are not obese.20-21 Several genetic loci are implicated. However, a specific gene defect is yet to be isolated in humans.
Thrifty Gene. The Pima Indians have a high incidence of obesity, which may be attributed to variable gene expression.22 Scientists use the "thrifty gene" theory proposed in 1962 by geneticist James Neel to help explain why many Pima Indians are overweight and obese. Neel's theory is based on the fact that for thousands of years, populations who relied on farming, hunting, and fishing for food (such as the Pima Indians) experienced alternating periods of feast and famine. To adapt to these extreme changes in caloric needs, these people developed a thrifty gene that allowed them to store fat during times of plenty so that they would not starve during times of famine. This gene was helpful as long as there were periods of famine. But once these populations adopted the typical Western lifestyle, with less physical activity, a high fat diet, and access to a constant supply of calories, this gene began to work against them, continuing to store calories in preparation for famine.23 Scientists think that the thrifty gene that once protected people from starvation might also contribute to their retaining unhealthy amounts of fat.
Racial Factors. Obesity is more prevalent in African American populations in the United States, especially in non-Hispanic black women.1 Some have attributed this to a lower metabolic rate as well as a lower fat oxidation rate in these women.24 In comparison, the prevalence of obesity in Asians is markedly lower, although it is rising with industrialization and technological advances.25
Genetic Defects. Autosomal recessive diseases like Prader-Willi syndrome and Laurence-Moon-Bardet-Biedl syndrome are known for manifesting obesity.26 Prader-Willi syndrome is characterized by hyperphagia, obesity, diabetes mellitus, hypotonia, and mental retardation.26 Laurence-Moon-Bardet-Biedl syndrome is characterized by hyperphagia, obesity, mental retardation, hypogonadism, retinitis pigmentosa, and polydactyly.26 Finally, several other genetic disorders such as Down syndrome, pseudo-hypoparathyroidism, and pseudo-pseudo-hypoparathyroidism also present frequently with obesity.26
Neurological. Obesity is frequently a clinical manifestation in a variety of neurological disorders. It is attributed to damage to the ventromedial portion of the hypothalamus.27 Obesity noted in subjects manifesting tumors such as craniopharyngioma, inflammation such as encephalitis, trauma, surgical injury, and increased intracranial pressure have been attributed to this pathophysiology. Damage to the hypothalamus is documented to induce hyperactivation of endocannabinoid system leading to hyperphagia and hyperinsulinemia, both of which promote weight gain resulting in obesity.28
Endocrine. Cushing's syndrome in adults causes characteristic centripetal obesity involving the face, neck, trunk, and abdomen.29 In children, it causes generalized obesity.29 Prolonged glucocorticoid therapy (60 days) frequently induces similar features.30 Hypothyroidism frequently causes weight gain by slowing the body's metabolism.31 Hypopituitarism may also result in obesity, probably secondary to hypothyroidism and hypogonadism.32 Finally insulinoma is one of the rare causes of weight gain.32-33
Drugs. Several drugs have been implicated in induction of obesity.34-35 Weight gain associated with prolonged administration of neuroleptics (i.e., thioridazine, clozapine, olanzapine, quetiapine, and risperidone) is frequently attributed to their effect on the hypothalamus.36 Haloperidol, ziprasidone, and aripiprazole may be suitable alternatives.36 Tricyclic antidepressants such as amitriptyline and nortriptyline cause weight gain by inducing cravings for food, mainly carbohydrates.37 Long-term use of selective serotonin reuptake inhibitors such as paroxetine may also cause weight gain.38 The older anticonvulsants such as carbamazepine and valproic acid, as well as other drugs including lithium and beta-blockers such as propranolol, are thought to cause obesity.34-35 Finally treatment with glucocorticoids, oral contraceptives, and progestins may induce obesity34, and anti-diabetic drugs (i.e, insulin, glitazones, and sulfonylureas) also frequently cause weight gain as a side effect.39
Idiopathic Factors. This group accounts for 95% of the causes of obesity.
Metabolic Process. There are several hypotheses regarding how altered metabolism may induce obesity. Some researchers believe that there is increased fat synthesis due to preferential shunting of nutrients into lipid-producing pathways.40 Others propose that the obese body has developed increased efficiency at extracting energy from nutrients and storage of extra calories.41 Alternatively, inhibition of mobilization of stored fats is another hypothesis responsible for induction of obesity.40
Hormonal Factors. Ghrelin is a hormone produced by the stomach that stimulates appetite, and leptin is a hormone produced by the adipocytes that induces satiety. It has been proposed that obese individuals are resistant to the action of leptin because high levels of leptin and low levels of ghrelin are well documented in obesity.41
Nutritional Factors. Overeating in adult life causes increased fat cell size (hypertrophic obesity) whereas overeating in early life leads to childhood obesity of hyperplastic variety (increased fat cell number).4 Maternal over-nutrition and smoking during pregnancy also are thought to increase infant birth weight, a distinct predisposing factor for childhood obesity.42
Physical Inactivity. A direct correlation is established between total daily energy expenditure and fat free mass. Overweight and obese individuals frequently suffer from osteoarthritis, chronic pain, self-consciousness, low self-esteem, and diminished respiratory drive leading to significantly reduced capacity and willingness to exercise, thereby perpetuating a vicious cycle resulting in further worsening of obesity.43
Psychological. Emotional factors like anxiety, frustration, boredom, and depression lead to frequent eating to obtain relief of stress, leading to obesity.44 Obese people are also perhaps more responsive to food-related stimuli such as smell, appearance, time of day, etc.45
Other Nonphysiologic Factors. Cultural or social factors (i.e., peer pressure for acceptance in the company of friends or relatives) frequently leads to overeating resulting in obesity.46 Finally, increased prevalence of obesity among highly affluent populations is attributed to diminished time for personal activity including exercise.47 Technological advances and work pressures may also play a part.
Complications
Mortality. Obesity is associated with increased overall mortality beginning at all ages until 50 years of age before reaching a plateau.48-49 Obesity in adulthood is also associated with a striking reduction in life expectancy for both men and women.48-49 Among 3457 subjects in the Framingham Study, obese individuals (BMI > 30 kg/m2) at age 40 years lived six to seven years shorter than those who were not (BMI < 24.9 kg/m2).50 Visceral obesity expressed by waist circumference is also significantly positively correlated with all cause mortality and with an even stronger correlation with cardiovascular deaths.51
Morbidity. Obesity has numerous health ramifications with complications involving every organ system in the body. (See Table 2.)
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Metabolic Disorders. Type II Diabetes Mellitus. Obesity is strongly associated with type 2 diabetes mellitus.52 More than 80 percent of patients with type 2 diabetes are obese in this country. A curvilinear relationship was found between type 2 diabetes and body mass index in the Nurses Health Study.53 Weight gain often precedes the diabetes. Type 2 diabetics who lose substantial weight are often cured of their hyperglycemia as clearly demonstrated in subjects losing substantial body weight following bariatric surgery.54
Dyslipidemia. Type IV lipoproteinemia or increased triglycerides or very low density lipoprotein (VLDL) secondary to increased synthesis and decreased degradation is the most common lipid abnormality induced by inhibition of insulin sensitive lipoprotein lipase.55 The same mechanism may also cause lowering of both high density lipoprotein (HDL) and low density lipoprotein (LDL). Moreover, obesity causes increased cholesterol synthesis and, less frequently, induces an increase in low density lipoprotein.55 Finally, the incidence of hyperuricemia and gout is also significantly increased in obesity.56
Cardiovascular Diseases. Obesity is associated with an increased incidence of coronary artery disease secondary to persistent dyslipidemia, diabetes mellitus, and hypertension.57-58 Increased demand on the heart due to increased body surface apparently leads to left ventricular hypertrophy, increased left ventricular end diastolic pressure, and ultimately congestive heart failure.59 Myocardial dysfunction secondary to increased fat deposition has also been demonstrated.59 Visceral fat distribution appears to be an important predictor of coronary artery disease. Many studies have demonstrated that a waist to hip ratio over 0.85 in women and 0.90 in men or the waist circumference over 35 inches in women and 40 inches in men is a reliable predictor of future cardiovascular events.16,60-61 Obesity leads to increased incidence of stroke, presumably due to hypertension and dyslipidemia.62 It is also a major risk factor for venous thrombosis and pulmonary embolism from diminished physical activity.63
Hypertension. In the Swedish obesity study, 50% of obese patients were hypertensive, whereas, in the Framingham heart study, the prevalence was between 26-28%, with a distinct significant correlation being noted in women.50,54 Blood pressure in obese patients must be measured with a larger cuff. The mechanism of obesity causing hypertension is yet unclear but is currently attributed to fluid retention.64
Endocrine Dysfunction. Metabolic Syndrome. Obesity, particularly abdominal obesity, is associated with insulin resistance with inhibition of both peripheral glucose and fatty acid utilization leading to hyperglycemia, dyslipidemia, and hypertension, three important characteristics constituting the metabolic syndrome.65-67 In the national healthy survey called NHANES III, metabolic syndrome was present in 5% in normal weight adults in contrast to 22% in overweight subjects, and 60% in the presence of obesity.68
Hypogonadism. Obesity is a leading cause of isolated hypogonadotropic hypogonadism.69 It leads to erectile dysfunction in men and menstrual irregularities in women (i.e., amenorrhea, anovulatory cycles).69-70 These abnormalities are attributed to altered hypothalamic pituitary gonadal axis in men and women as well as increased peripheral conversion of estrogen to androgens in women.70 Obesity also has a well-known association with polycystic ovary syndrome.71
Other endocrine abnormalities include altered thyroid hormone metabolism causing increased serum triiodothyronine and decreased serum reverse triiodothyronine levels, increased cortisol production despite maintaining normal hypothalamic pituitary adrenal axis.72 Finally, decreased human growth hormone response to provocative stimuli such as arginine or insulin-induced hypoglycemia has also been described.73
Pulmonary Dysfunction. Obstructive Sleep Apnea. Fat deposition causing pharyngeal compression leads to upper airway obstruction, especially in recumbent position resulting in oxygen desaturation during sleep.74 Moreover, a restrictive component (e.g., increased abdominal pressure on the diaphragm) induces alveolar hypoventilation. Finally, obesity also adds insult to injury by reducing lung compliance due to a progressive increase in total mechanical work of breathing. The ultimate outcome is a state of chronic hypoventilation with CO2 retention and narcosis also described as Pickwickian syndrome.75 This syndrome usually occurs in the presence of severe obesity and is characterized by chronic respiratory acidosis with hypoxemia and manifests with dyspnea, hypersomnolence, markedly reduced exercise tolerance, fatigue, lethargy, and cyanosis. Finally, grave consequences of pulmonary hypertension and right ventricular failure ensue resulting in reduction in life span.75
Gastrointestinal. Hiatal hernia is common secondary to lack of support of the esophagus as a result of fat deposition in diaphragm.76 The incidence of gallstones is also increased most probably secondary to elevation in serum cholesterol.77 Constipation and non-alcoholic steatohepatitis (NASH) causing mild elevation of liver transaminases are also frequent occurrences.78-79
Miscellaneous. Osteoarthritis of hips, knees, and ankles is extremely common and is attributed to wear and tear from weight bearing.80 Skin changes like hirsutism, striae, and acanthosis nigricans are also noted.81 Finally, the prevalence of malignancies is documented to rise in the obese population with significant correlations being demonstrated with cancers of the breast, prostate, uterus, esophagus, colon, liver, gallbladder, pancreas, and kidney as well as lymphoma and multiple myeloma.82 Moreover, one study demonstrated that 14-20% of all cancer deaths in a population could be attributable to obesity.82 Other miscellaneous complications include high prevalence of renal calculi compared to lean individuals83 as well as obstetrical problems like toxemia of pregnancy, hypertension, prolonged labor, and miscarriages.84 Finally, obese patients are more prone to low self-esteem and depression resulting in suicides as well as accidents.85-86
Management
Body weight is maintained by the balance of anabolism and catabolism. Therefore, a simple approach to treatment of obesity revolves around two options: to decrease anabolism and to increase catabolism. Anabolism can be decreased by either reducing caloric intake or by reducing caloric absorption, whereas increased catabolism is promoted by raising the level of activity. Decreased caloric intake can be achieved by dietary restriction with widely available "weight loss" diets. The same objective may also be attained through drugs or surgical procedures as an adjunct to the diet. An increase in weight loss is attained and maintained by regular exercise.
Diet and Behavior Modification
Dietary restrictions and behavior modification are the most crucial steps in management of obesity. Several counseling sessions are necessary for behavior modification with emphasis on self-monitoring of all eating patterns and establishment of control over eating environment.87 It is extremely important to establish guidelines to achieve control of cues and engage in planned manipulation of eating responses, e.g., contingencies and "rewards." Continuing behavior modification may help achieve and maintain weight loss. Recently, a monetary reward for weight loss as opposed to equivalent monetary punishment for weight gain apparently has improved compliance with diet and exercise resulting in substantial weight loss.
Various methods may be employed to estimate approximate caloric requirement for the individual subjects. The most common method used to estimate daily caloric intake to maintain body weight is to allot 10 calories per pound or 22 calories per kg of present body weight for subjects resting in bed.88 The daily caloric requirement increases for the level of activity as follows: 20-25% for minimal ambulation, 40-50% for sedentary job, 70-75% for moderate activity, and 75-100% for extreme activity as performed by a construction worker.
Approximately 50-60% of total body weight consists of lean body mass made up of protein and the rest is adiposity with a minimal contribution by carbohydrate in the form of glycogen. One kilogram of protein or carbohydrate contributes 4000 kilocalories (kcal), whereas 1 kg of fat contributes 9000 kcal. Therefore, a change in body weight of 1 kg involves change in the caloric intake of about 7000 kcal. Thus one could obtain a weight loss of 1 kg/week with reduction in weekly intake by 7000 kcal, and 3500 kcal needs to be reduced per week to obtain a weight loss of about 1 pound. This is the basis of weight reduction diets that are widely advertised. The various "weight loss" diets range from almost total starvation to those with daily kilocalorie intake based on the desired weight loss over a certain period of time as described above.
Starvation is a caloric intake of less than 200 kcal/day and is not medically indicated because, in the long term, it is potentially dangerous and can lead to clinically significant ketosis; electrolyte derangements; vitamin, mineral and other micronutrient deficiencies; and a marked potential for morbidity and mortality. Moreover, starvation is not validated as an effective method of achieving substantial and sustained weight loss. Similarly, very low-calorie diets (VLCDs) are not recommended unless conducted in an established, comprehensive program. VLCDs involve reduction in daily caloric intake of 800 kcal or less. When used in optimal settings, these diets are able to achieve weight loss of 1.5-2.5 kg/wk, with a total loss of as much as 20 kg over 12 weeks depending on initial body weight at the time of enrolling in the program.89-90
Other more conventional diets are broadly classified as balanced, low-calorie diets (or reduced portion sizes); low-fat diets; low-carbohydrate diets; midlevel diets (e.g., Zone diet, in which the 3 major macronutrients [fat, carbohydrate, protein] are eaten in similar proportions of 30-40%); and fad diets.
Balanced LCDs or reduced portion sizes diets are frequently prescribed by nutritionists and other weight-management professionals because of their established efficacy and safety. These diets form the basis of the popular, commercial weight-loss programs such as those advocated by Jenny Craig, Weight Watchers, Take Off Pounds Sensibly (TOPs), and Overweight Anonymous. Low-calorie diets involve a caloric intake of 800-1200 kcal/d and are associated with a mean weight loss of 0.4-0.5 kg/wk, with a total loss of 6-8 kg in ideal settings.89-90 With any low-calorie diet, maintaining intake of protein with high biologic value of >1 g/kg is vital to preserve lean body mass. Furthermore, the subjects consuming these as well as very low calorie and total starvation diets must be monitored for potential complications (e.g., vitamin deficiency, ketosis, and its manifestations of nausea and vomiting, as well as electrolyte derangements, hyperuricemia with gout, and cholelithiasis). Therefore, diets with fewer than 1500 kcal/day must be supplemented with vitamins and minerals. Although these diets are useful for short-term weight loss, none alone is associated with reliable, sustained weight loss.89-90
The recommended composition for the best-validated dietary programs are protein intake of 0.8-1.5 g/kg of body weight (not to exceed 100 g/d), 10-30% of total calories from fat (preferably > 90% as polyunsaturated fat and < 10% as saturated fat), carbohydrate intake of > 50 g/d, and water intake of > 1 L.89-90
In two randomized trials, weight loss with Atkins-type diets were compared with conventional low-fat or balanced calorie-deficit diets.91-92 Although the Atkins-type diet had the greatest initial weight loss, weight loss became similar within 1 year. Furthermore, although serum lipids did not appear to be deleteriously affected, the period of observation was only about a year, and noncompliance rates in the Atkins-type group was close to 50%.
The South Beach Diet is another low-carbohydrate that is more liberal than the Atkins Diet in its carbohydrate allowance; therefore, compliance rates are enhanced. The South Beach Diet distinguishes between carbohydrates as good and bad carbohydrates on the basis of their glycemic index.93
Dansinger and colleagues compared the Zone, Ornish, and Atkins diets with a typical balanced, calorie-restricted (Weight Watchers) diet.94 The Ornish, very-low-fat, and Atkins diets had the poorest compliance rates. The researchers observed no significant differences in weight loss with the individual diet. Compliance and caloric deficits were more important predictors of weight loss and improvement in cardiovascular risk surrogate markers than specific dietary composition.
Exercise
A good exercise program must be followed for achieving and maintaining weight loss.95 In general, there are several potential benefits of increased exercise and physical conditioning in the management of obesity.96 These include increased caloric expenditure leading to negative energy balance, change in body composition with increased ratio of lean body mass to fat, better cardiovascular conditioning, and improvement in basal metabolism. Finally attempts have been made to increase catabolism by hormones like HCG, thyroid hormones, steroid hormones, glucagon, etc.
Drugs
Drug therapy may be a useful adjunct to dietary restrictions and exercise in obesity management. Weight loss achieved with medications rarely exceeds 10-15% and the weight is regained once medications are discontinued.97-98 Thus, the patient and the provider must arrive at a realistic understanding and expectations of drug therapy. The two main classes of drugs are appetite suppressants and medications that alter the digestion. Table 3 summarizes the main clinical studies and the Food and Drug Administration (FDA) approval status of these drugs.
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Sibutramine, a reuptake inhibitor of serotonin and norepinephrine, induces mean weight loss of about 4.45 kg resulting in decreases in hyperglycemia, triglycerides, and LDL with an increase in HDL.99-100 Being a sympathomimetic, side effects include increase in blood pressure and heart rate and, therefore, it should be avoided in patients with coronary artery disease, hypertension, and congestive heart failure.
Orlistat inhibits pancreatic lipase causing excessive fecal fat excretion. In meta-analysis of clinical trials using orlistat, the mean weight loss was about 2.75 kg.101 As expected, the most common side effects are diarrhea, flatulence, and abdominal cramps, with fecal incontinence being an occasional occurrence. Side effects may be minimized by reducing oral fat intake to less than 30 g. Combination therapy with sibutramine and orlistat have failed to achieve greater weight loss than with a single agent alone.102
Phentermine is the only noradrenergic drug approved by FDA for the short-term treatment of obesity. It acts by stimulating central release of norepinephrine. It can cause tachycardia and palpitations. In one trial, it led to a mean weight loss of about 22 pounds compared to placebo over a 24 week period.103
Fluoxetine is another selective serotonin reuptake inhibitor used to treat depression. In clinical trials with this agent, a mean weight loss of about 4.5 kg at 6 months and 2.2 kg at one year was documented.104 However, it is not FDA approved for weight loss.104 Similarly, several other drugs have been shown to be efficacious in inducing a moderate weight loss in clinical trials awaiting approval by FDA. One of the most promising such agents is rimonabant, a cannabinoid receptor antagonist that has been approved in Europe, Canada, and Mexico to treat obesity.105-106
Surgery
Various types of surgical procedures have been performed to treat obesity and achieve weight loss. To qualify for surgery, the subject must be well informed and motivated with a BMI more than 40 kg/m2 or more than 35 kg/m2 with severe diabetes, sleep apnea, or joint disease. Moreover, the subjects must have failed previous non-surgical weight loss regimens and must be an acceptable risk for surgery.107
The procedures involve the GI tract and are classified into two types, i.e., malabsorptive and restrictive. The jejuno-ileal bypass was one the earliest performed malabsorptive bariatric surgeries. This surgery creates a short-gut anatomy by connecting proximal small bowel to the terminal ileum. Thus, it left only about 20 inches of small bowel for the digestion and absorption of nutrients. It has fallen out of repute because of extensive complications including maldigestion and malabsorption of all nutrients resulting in vitamin deficiencies, diarrhea, liver failure, and death.108 Another malabsorptive surgical procedure involves biliopancreatic diversion performed by partial gastrectomy and gastroileostomy with a Roux-en-Y limb. Side effects include protein malnutrition, anemia, and diarrhea.109
More recently, however, the malabsorptive surgical methods have given way to various restrictive procedures other than the now-obsolete jaw wiring. These include gastric partitioning with vertical banded gastroplasty, laparoscopic gastric banding, partial sleeve gastrectomy, gastric balloon, and Roux-en-Y gastric bypass. Vertical banded gastroplasty (VBG) involves partitioning of the upper part of the stomach by a vertical staple line with a tight outlet wrapped by a prosthetic mesh or a band. Weight loss occurs as a result of intolerance to eating solid big meals.110-111 Complications include staple line disruption, stomal stenosis, band erosion, band disruption, pouch dilatation, vomiting, gastro-esophageal reflux disease, and inability to maintain sustained weight loss.111 Laparoscopic gastric banding (LAGB) is a purely restrictive procedure that compartmentalizes the upper stomach by placing a tight, adjustable prosthetic band around the entrance to the stomach.112-114 The band consists of a soft, locking silicone ring connected to an infusion port placed in the subcutaneous tissue. The port may be accessed with relative ease by a syringe and needle. Injection of saline into the port leads to reduction in the band diameter, resulting in an increased degree of restriction. LAGB is contraindicated in patients with Crohn's disease, large hiatal herniae, portal hypertension, connective tissue disorders, and prior gastric ulcers. Effective weight loss of 45-75% at two years has been documented with this procedure.112-114 Sleeve gastrectomy consists of a laparoscopic partial gastrectomy in which the majority of the greater curvature of the stomach is removed and a tubular stomach is created. This procedure enables surgeons to perform initially the technically less challenging partial gastrectomy while delaying the technically more rigorous laparoscopic biliopancreatic diversion to a later time after some weight loss.115 The mixed gastric balloon procedure consists of a soft, saline-filled balloon placed endoscopically to promote a feeling of satiety and restriction. It is currently not available for use in the United States. Mean weight loss is reported to be 38-48% of initial body weight over a year.116 Finally, Roux-en-Y gastric bypass is characterized by a small (less than 30 mL) proximal gastric pouch divided and separated from the stomach remnant with drainage of food to the rest of the gastrointestinal tract via a tight stoma and a Roux-en-Y small bowel arrangement. Weight loss varies from 60-75% of the initial body weight and is usually sustained over a long-term period.117
Complications of restrictive procedures include acute stomal obstruction, band erosion, band slippage/prolapse, port/tubing malfunction, pouch/esophageal dilatation, esophagitis, and infection.118-119 Complications of gastric bypass include pulmonary embolus, leaks, bleeding, gastric remnant distention, wound infection, stomal stenosis, marginal ulcers, cholelithiasis, ventral or incisional and internal herniae, as well as metabolic and nutritional derangements.118-119
Compared to diet, exercise, and drugs, which produce a weight loss of 5-10% for about 5 years, bariatric surgery has been shown to produce a consistent weight loss of 50-75% that is well maintained for 10-15 years.120 Bariatric surgery is successful not only because of the anatomical changes made but also because of biochemical changes that occur in the gastrointestinal system such as an increase in levels of incretins and glucagon-like peptides.121 It also leads to substantial improvement in hypertriglyceridemia, hypertension, hyperuricemia, sleep apnea, and type 2 diabetes mellitus. In one meta-analysis, more than two-thirds of all surgical patients had complete resolution of their diabetes, hypertension, and obstructive sleep apnea.120 The many successes of bariatric surgery in adults form the basis of treatment of obesity and its co-morbid conditions in adolescents.
Newer Approaches. Since the hypothalamus is central to the regulation of energy balance and the action of leptin, several researchers are trying to develop pharmaceutical agents that specifically target this area.122 Some neurosurgeons are using selective ablation as a kind of functional surgery to reduce appetite and hyperphagia, although literature is scant in this regard.
Conclusion
In summary, obesity is a dormant volcano of dire health consequences ready to erupt on our nation's health infrastructure, particularly with the growing aging baby boomers and rising prevalence of metabolic syndrome in both children and adolescents. Primary care providers should use current knowledge and understanding of obesity to aggressively pursue weight loss measures and techniques to lower the morbidity and mortality affecting all ages of all sections of society. This is a matter of great public health importance and poses a great challenge to the health care system. A collective effort on behalf of the governments at all levels including schools, voluntary organizations, and media in public health education as well as using all the available community health resources will be essential in slowing the progress of this epidemic.
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The prevalence [of obesity] in both adults and children is reaching epidemic proportions and has led to a prediction by CDC that the life expectancy in this country would start declining in the next 20 years. In fact, according to CDC, it has already fallen in a couple of states as reported recently in the news media.Subscribe Now for Access
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