Diabetes Mellitus: A Fundamental and Clinical Text
3rd Edition
© 2004 Lippincott Williams & Wilkins
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56
Obesity: Treatment
Xavier Pi-Sunyer
Obesity is increasing in prevalence in the United States (1) and around the world (2). Associated with this increase there has been a corresponding increase in type 2 diabetes mellitus (3) and the metabolic syndrome (4). Other health risks have been associated with obesity, including hypertension, dyslipidemia, coronary artery disease, stroke, sleep apnea, gallbladder disease, and joint disease (5). In particular, central obesity has been characterized in epidemiologic studies as being particularly and independently associated with health risk for diabetes and coronary artery disease (5,6,7,8,9,10,11).
Because of this alarming situation, the treatment and prevention of obesity has become a high priority in medicine and public health. The treatment recommendation is based on two premises: that weight can be lost and the lower weight maintained, and that this will improve health (12). There is now evidence from a number of randomized trials that a significant amount of weight can be lost and then about two thirds of this loss can be maintained (2,13,14,15). However, this is a difficult endeavor, and the failure rate is high. Great motivation and commitment are required by the patient, but support and practical help by the physician are also necessary.
Physicians are used to giving drugs for most of the diseases that they treat, and they are not as comfortable with treating a condition that requires a great deal of patience, numerous visits, and slow and often unimpressive results. Because of this, much of the treatment of obesity is done by other health professionals, including nutritionists, nurses, psychologists, and exercise physiologists. Although these individuals are often better attuned to the task at hand, there should always be some physician oversight of the treatment program. This is important for treating associated risk factors that are initially present or adverse effects that occur during the course of treatment.
Assessment
The initial step in treatment is assessment of the patient. An initial evaluation by the physician will allow an appropriate treatment plan to be developed. Although the degree of obesity can be detected generally by a quick visual inspection, it is important to track quantitative data as treatment progresses. The body mass index (BMI) is a good way to track body mass. It is calculated by dividing the weight in kilograms by the height in meters squared (kg/m2) (16) (Table 56.1). Although the correlation between BMI and fatness is not ideal, particularly at lower BMI levels, it is good enough for the clinical follow-up of patients (13,17). The National Institutes of Health has classified normal, overweight, and obese into categories (13) (Table 56.2). Although these categories have also been adopted by the World Health Organization (2), the upper limit of 25 for normal weight has been considered too high by some Asian groups, who consider their populations at greater health risk at lower BMI levels (18). Table 56.3 (13) gives BMI levels for given heights and weights.
Because of the increased risk of central fat, the physician also needs to assess and follow a measurement of central fatness. The easiest and cheapest is the waist circumference (13). Measuring waist circumference is described in Fig. 56.1 (13). It can be done with a fiberglass tape measure as described in the legend to Fig. 56.1. The relationship of waist circumference to health risk is shown in Table 56.4 (13). Waist circumference correlates quite well with computed tomographic measures of area of central fat (19).
Weight Loss and Health Risk
The relationship of weight loss to health risk has been difficult to study because many individuals lose weight when they are ill. As a result, intentional weight loss has to be separated from unintentional weight loss in outcome studies. Williamson et al. (20) have reported, in a retrospective analysis of an American Cancer Society cohort, that intentional weight loss decreases all-cause and cardiovascular mortality.
There are a great many short-term studies that have shown that weight loss reduces health risks (21,22,23,24,25,26,27). Examining type 2 diabetic patients in particular, Wing et al. reported on a longer-term study (1 year) in which the whole cohort lost 5.6 kg while on active intervention and then maintained a loss of 4.5 kg at 1 year (28). Glucose and insulin levels decreased with weight loss (Table 56.5). Those who lost the most weight had the greatest effect on hemoglobin A1C (Table 56.5). This occurred even though these patients’ weights still remained 20% above normal. The effect on glucose and insulin is complicated by the fact that a substantial number of patients had either insulin or other oral agents reduced during the trial. Numerous studies
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have shown that long-term weight loss decreases morbidity, as reviewed by Pi-Sunyer (29).
Table 56.1.
In the United Kingdom Prospective Diabetes Study (UKPDS), newly diagnosed patients with type 2 diabetes were initially started on a weight loss program. The weight loss necessary to achieve normalization of fasting plasma glucose (FPG) was 16% of ideal body weight in patients with initial FPG values of 6 to 8 mM, 21% percent in those with levels of 8 to 10 mM, 28% in those with levels of 10 to 12 mM, and 41% in those with levels greater than 14 mM (30). Of 3,044 individuals, at the 15-month period 482 patients maintained normal FPG levels. One must remember, however, that many who were not able to maintain normal FPG levels required treatment with hypoglycemic agents (30). Most often, in fact, over time, patients with type 2 diabetes will require drug therapy in addition to the weight loss program (31).
Recently there have been a series of studies that have shown the importance of lifestyle change on progression to diabetes in persons with impaired glucose tolerance (IGT). These include the Da Qing study (32), the Diabetes Prevention Study in Finland (14), and the Diabetes Prevention Program (DPP) in the United States (15). In these studies, diet and exercise were used to reduce weight a modest amount and keep it off. The goal was a loss of 5% from baseline in the Finnish study and 7% from baseline in the DPP. The progression of IGT to diabetes was greatly reduced in all three trials, in the latter two by 58% in 5 years.
Table 56.2. Classification of overweight and obesity by body mass index (BMI)
  Obesity class BMI (kg/m2)
Underweight   <18.5
Normal   18.5–24.9
Overweight   25.0–29.9
Obesity I 30.0–34.9
II 35.0–39.9
Extreme obesity III ≥40.0
The effect of weight loss on reducing blood pressure has also been shown in a number of randomized clinical trials (33,34,35,36,37,38,39,40,41,42,43,44). The effect has led to the recommendation that the initial treatment for a hypertensive patient is lifestyle change (45).
Obese and obese type 2 diabetic individuals tend to suffer from a triad of low triglycerides, elevated high-density lipoprotein (HDL) cholesterol, and LDL particles that are small, dense, and atherogenic (46,47). All three components of this triad improve quickly with weight loss (21,48,49,50,51,52,53). Longer-term studies also show this improvement (35,38,54,55,56,57).
There have been few good studies of the effect of intentional weight loss on cardiovascular risk. To obtain hard end points, very long-term studies need to be undertaken. Two secondary prevention year-long studies have suggested an effect. The first, a one-year trial in a group of patients who experienced a myocardial infarction (58), and another on the effect of the Mediterranean diet on progression of coronary disease (59), are suggestive.
Respiratory function is often impaired in obese persons, particularly as the severity of the obesity increases (5). Weight loss has been reported in a number of studies to greatly improve respiratory function, with reduced apneic episodes and better sleep patterns (60,61,62,63,64,65).
There is evidence that gallstones are more common in overweight and obese persons (5). When a person is in the process of losing weight, the risk for gallstones and cholecystitis increases, due to an increased supersaturation of bile with cholesterol and a hypotonia of the gallbladder (66,67,68,69). However, once weight loss is achieved, the risk of gallstone formation decreases (68).
Table 56.3. Body mass index (BMI) chart
  19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35   36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54
Height (inches) Body weight (pounds)
58 91 96 100 105 110 115 119 124 129 134 138 143 148 153 158 162 167 58 172 177 181 186 191 196 201 205 210 215 220 224 229 234 239 244 248 253 258
59 94 99 104 109 114 119 124 128 133 138 143 148 153 158 163 168 173 59 178 183 188 193 198 203 208 212 217 222 227 232 237 242 247 252 257 262 267
60 97 102 107 112 118 123 128 133 138 143 148 153 158 163 168 174 179 60 184 189 194 199 204 209 215 220 225 230 235 240 245 250 255 261 266 271 276
61 100 106 111 116 122 127 132 137 143 148 153 158 164 169 174 180 185 61 190 195 201 206 211 217 222 227 232 238 243 248 254 259 264 269 275 280 285
62 104 109 115 120 126 131 136 142 147 153 158 164 169 175 180 186 191 62 196 202 207 213 218 224 229 235 240 246 251 256 262 267 273 278 284 289 295
63 107 113 118 124 130 135 141 146 152 158 163 169 175 180 186 191 197 63 203 208 214 220 225 231 237 242 248 254 259 265 270 278 282 287 293 299 304
64 110 116 122 128 134 140 145 151 157 163 169 174 180 186 192 197 204 64 209 215 221 227 232 238 244 250 256 262 267 273 279 285 291 296 302 308 314
65 114 120 126 132 138 144 150 156 162 168 174 180 186 192 198 204 210 65 216 222 228 234 240 246 252 258 264 270 276 282 288 294 300 306 312 318 324
66 118 124 130 136 142 148 155 161 167 173 179 186 192 198 204 210 216 66 223 229 235 241 247 253 260 266 272 278 284 291 297 303 309 315 322 328 334
67 121 127 134 140 146 153 159 166 172 178 185 191 198 204 211 217 223 67 230 236 242 249 255 261 268 274 280 287 293 299 306 312 319 325 331 338 344
68 125 131 138 144 151 158 164 171 177 184 190 197 203 210 216 223 230 68 236 243 249 256 262 269 276 282 289 295 302 308 315 322 328 335 341 348 354
69 128 135 142 149 155 162 169 176 182 189 196 203 209 216 223 230 236 69 243 250 257 263 270 277 284 291 297 304 311 318 324 331 338 345 351 358 365
70 132 139 146 153 160 167 174 181 188 195 202 209 216 222 229 236 243 70 250 257 264 271 278 285 292 299 306 313 320 327 334 341 348 355 362 369 376
71 136 143 150 157 165 172 179 186 193 200 208 215 222 229 236 243 250 71 257 265 272 279 286 293 301 308 315 322 329 338 343 351 358 365 372 379 386
72 140 147 154 162 169 177 184 191 199 206 213 221 228 235 242 250 258 72 265 272 279 287 294 302 309 316 324 331 338 346 353 361 368 375 383 390 397
73 144 151 159 166 174 182 189 197 204 212 219 227 235 242 250 257 265 73 272 280 288 295 302 310 318 325 333 340 348 355 363 371 378 386 393 401 408
74 148 155 163 171 179 186 194 202 210 218 225 233 241 249 256 264 272 74 280 287 295 303 311 319 326 334 342 350 358 365 373 381 389 396 404 412 420
75 152 160 168 176 184 192 200 208 216 224 232 240 248 256 264 272 279 75 287 295 303 311 319 327 335 343 351 359 367 375 383 391 399 407 415 423 431
76 156 164 172 180 189 197 205 213 221 230 238 246 254 263 271 279 287 76 295 304 312 320 328 336 344 353 361 369 377 385 394 402 410 418 426 435 443
To use the table, find the appropriate height in the left-hand column. Move across to a given weight. The number at the top of the column is the BMI at that height and weight. Pounds have been rounded off.
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Therapeutic Goals
Because of the associated health risks of obesity, and because of the amelioration of risks with weight loss, the therapeutic goal for managing the overweight and obese patient is to achieve a certain amount of weight loss and then to maintain it over time. In setting weight loss goals, it is important to be aware that patients have faulty ideas about weight loss. Most want to lose much more weight than they realistically can and are dissatisfied on losing less (70). It is important to go into some detail with a patient about the expected amount of weight that he or she can realistically take off and maintain. Whereas years ago the goal was to try to get patients to normal weight, this is no longer being attempted. The aim is for a healthier weight that will reduce risk factors to a significant degree. A number of recent guidelines have suggested a loss of about 10% from baseline weight (13,71,72). This is realistic, attainable, and maintainable (13,29). A goal, therefore, of no more than 10% or 15% loss from baseline weight should be set. Setting a larger goal will only bring disappointment and anger. If an individual can lose this amount of weight and keep it off for a period of a year, then further weight loss may be attempted. It will be a rare individual who will be able to do this. Although some patients can lose significantly more than this with very low-calorie diets, they quickly revert back to their original weight when this diet is terminated (73).
Nutrition
Nutrition is the most important component of a weight loss program. Obese patients are consuming a large number of calories daily (74), and these must be reduced, not only during the weight-loss period, but also during the weight-maintenance period. This requires focus on a number of points: the total caloric content of the diet, the macronutrient content, and the micronutrient content of the diet.
Calories
Obesity occurs in an individual because energy intake is greater than energy expenditure. The excess energy is primarily stored as fat. The strategy for weight loss is to reverse this and thereby to take energy out of fat stores. Thus, producing a caloric deficit is the most important item in a weight loss program. A reasonable aim is for a caloric deficit of 500 to 1,000 kcal per day.
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One kilogram of lost weight is about 7,000 kcal (75). Thus, a deficit of 700 kcal per day translates to a weight loss of 1 kg in 10 days. If the deficit is 500 kcal, it will take 14 days; if it is 1,000, it will take 7 days. This is quite predictable, although initially more weight may be lost because of a water diuresis. Such a deficit has now been shown to be successful in a number of trials (14,15).
Weight loss occurs for about 4 to 6 months and then plateaus. The plateau is due to a new equilibrium where energy intake once again is equivalent to energy expenditure. At this point, hopefully with a 10% to 15% weight loss from baseline, it is wise to concentrate on weight maintenance. This will require continuing the same energy intake that a patient has been ingesting and a physical activity at least as great as a patient has been doing as he or she plateaus. There can therefore be no liberalization of food intake or reduction in physical activity, or else weight regain will occur.
Macronutrient Content
The macronutrient content of the diet is the most controversial component in a weight-loss program. Because losing weight is so difficult, and patients as well as doctors are so frustrated with results, all types of special diets have been proposed as being ideal for weight loss. The four most common are the low-fat balanced diet, the Mediterranean diet, the low-carbohydrate/ high-fat diet, and the high-carbohydrate/low-fat diet.
Low-Fat Balanced Diet
This is the diet that was used in the DPP (15) and the Finnish Diabetes Prevention Study (14), and that has been recommended by the American Diabetes Association, the American Heart Association, and the American Dietetic Association. It consists of a diet that aims at a daily 500- to 1,000-calorie deficit. With this, fat is decreased at least to below 30% of total calories and an effort is made to decrease it to below 25%. Saturated fat is set at less than 7%, monounsaturated at less than 15%, and polyunsaturated at less than 7% of total calories. Protein is at 15% and carbohydrates at 55% to 60%. This diet aims at 200 mg cholesterol per day and at least 15 g of fiber. It is high in grains, fruits, and vegetables and low in meats and dairy products (13,14,15).
The Mediterranean diet is similar to the above diet, except it is more liberal on fat and decreases the amount of carbohydrates. The extra fat added in place of carbohydrate is monounsaturated
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and comes primarily from olive oil, olives, avocados, and nuts. It is more liberal in lean meat and dairy products (76).
Figure 56.1. Measuring tape position for waist (abdominal) circumference.
Table 56.4. High-risk waist circumference
Men: >40 inches (>102 cm)
Women: >35 inches (>88 cm)
The low-carbohydrate/high-fat diet is one that initially eschews carbohydrates almost totally (<5 g/day) and then allows no more than 50 g per day (77,78). It is about 25% to 30% protein, 55% to 65% fat, and 10% or less carbohydrate. It is a ketogenic diet that is high in meat and dairy products and as a result is also high in cholesterol and saturated fat (79).
The high-carbohydrate/low-fat diet is one that eschews fat and allows a great deal of carbohydrate (80,81). It is a diet that only has about 10% to 15% of energy as fat, 15% as protein, and 75% as carbohydrates. It is low in meat, oils, and dairy products, but very high in grains, fruits, and vegetables.
There have been long-term trials (1 year or more) on both the low-fat balanced diet and the Mediterranean diet that have shown both their effectiveness and their safety (14,15,59). One
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long-term trial on the high-carbohydrate/low-fat diet (82) showed its effectiveness and safety over time. There have been no long-term trials on the low-carbohydrate/high-fat diet, although a recent abstract has suggested success at 12 weeks (83). In fact, there is little arguing that all of the diets can work on a short-term basis. What they all require is a motivated patient with the ability to comply with the diet and maintain the effort over a significant period of time.
Table 56.5. Weight loss, glucose, insulin, and hemoglobin A1 in obese type 2 diabetic patients undergoing weight loss
Weight loss (kg) n HbA1 (%) FBG (mg/dL) Insulin (U/mL)
Gained 23 0.1 +30 -29
0–2.3 22 0.6 +6 -26
2.4–6.8 42 0 -6 -46
6.9–13.6 21 -1.1 -29 -46
>13.6 6 -2.6 -77 -130
Micronutrient Intake
It is important that patients as they are losing weight maintain an adequate intake of micronutrients. Initially, with diuresis, they may lose significant amounts of sodium and potassium. With a balanced diet, they will be able to compensate for this. With unbalanced diets, replacement may be necessary. Most vitamins and minerals can be adequately maintained with a multivitamin tablet a day. Calcium should be supplemented at 1,000 mg per day and vitamin D at 400 IU per day to prevent bone mineral loss (84). With a very low-fat diet, supplementation with fat-soluble vitamins is advised.
Long-Term Advantage of a Balanced Diet
I believe that a low-fat balanced diet (Mediterranean or no) is the best strategy for weight loss. The emphasis here is on getting away from energy-dense foods and increasing grains, fruits, and vegetables. It also places an emphasis on choosing micronutrient-dense foods and not empty calorie foods, such as sugar and alcohol. By selecting from the grain, fruit, and vegetable groups, cutting down on the number of servings from meat, milk, and fat groups, adequate levels of micronutrients can be taken, as can adequate protein. Patients should be encouraged to take a wide selection of foods. This will make the diet more interesting and less boring, and will lead to a greater likelihood of compliance long-term. Also, it is superior to the low-carbohydrate/high-fat diet because it limits cholesterol and saturated fat, dietary risk factors for raising blood cholesterol and inducing coronary artery disease. Obese patients and particularly obese type 2 diabetes mellitus patients are at high risk from coronary artery disease (85). It seems counterintuitive and unsafe to place them on a diet that will increase their risk for coronary artery disease. In addition, the low-carbohydrate/high-fat diet has been shown to increase calcium loss (86). There are two dangers from this: a loss of bone mineral integrity (86) and the possible formation of kidney stones (86).
Other Strategies of a Nutrition Plan
Alcohol and sugar carry no micronutrients and are very energy dense. They should be eliminated or kept to a minimum in a weight-loss diet. The energy density of other foods should be noted. Foods that are high in fat or low in water tend to be highly energy-dense foods. By eating a small volume, a patient is ingesting a great many calories. An important strategy for weight loss is therefore to eat less energy-dense foods.
Formula diets can be helpful in weight loss. Many weight- loss programs now begin patients on a weight-loss program by taking them off regular foods and placing them on liquid formulas. This is continued for 12 to 24 weeks and then food is gradually returned, first at one meal, then two, then all. This has been a quite successful approach in some people (87,88).
Very low-calorie diets (300–500 kcal) were widely used in the past but have been found to be unsuccessful in the long run (73). Although there may be initial success, this is usually short lived (89). Most patients lose a great deal of weight but regain it quickly when they stop the very low-calorie diet and return to normal food. Diets lower than 800 kcal per day are now considered counterproductive to long-term weight maintenance.
Cutting down on portion sizes is crucial to success. Portion sizes in our society have been going up steadily for years, and we now eat many more calories at a sitting than in the past. A conscious effort to scale down is necessary.
Caloric beverage intake has gone up enormously in this country. Not only are people taking caloric beverages with all three meals, they are also taking them between meals. Much of the excess caloric intake of obese persons is due to this. The elimination or great curtailment of this habit is necessary to achieve success in weight loss and maintenance.
The protein in the diet should be appropriate for maintenance of optimal protein balance. With weight loss, there is a loss not only of fat, but also of fat-free mass (90,91,92). But this loss of fat-free mass, that is, protein, should be kept as low as possible. This can be done with an intake of protein at the level of 1.0 to 1.5 g/kg of ideal body weight. The ideal body weight can be calculated using a BMI of 25 and finding the appropriate weight for height in Table 56.2. The protein should be of high biologic value. Appropriate foods would be egg whites, fish, poultry, lean beef, and low-fat dairy products. A vegetarian diet is possible, but protein complementation must be practiced to ensure appropriate essential amino acid intake (93).
Exercise
Physical activity leads to greater health and longevity, so it is appropriate for everyone (94). Decreased physical activity has been associated with an increased risk for diabetes, coronary heart disease, and stroke (95,96,97). Also, lack of fitness leads to greater cardiovascular and all-cause mortality (98,99,100). Physical activity is particularly important for individuals trying to lose weight or maintain a weight loss. Physical activity expends energy, and increasing energy expenditure is a cardinal goal for success. Persons who are overweight and obese tend to be inactive. Exercise enhances insulin sensitivity and improves glucose tolerance (101,102). The more intense the exercise, the greater the effect (103). Also, resistance exercise can be helpful, as can aerobic exercise (104). A number of epidemiologic studies have reported the benefit of physical activity in preventing or retarding the onset of type 2 diabetes (95,104,105,106,107,108,109). Exercise also lowers blood pressure, whether weight is lost or not (110). Exercise has also been shown to improve lipid profiles (111).
Whether increased physical activity can actually enhance weight loss is widely debated. Wing (112), in a recent review of 13 randomized clinical trials of weight loss with and without an
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exercise component, found only two that demonstrated a significantly greater weight loss in the group that exercised. She also reviewed four studies that had a resistance exercise component and again found no statistically greater weight loss with exercise (112).
There has been less controversy as to whether exercise is helpful for weight maintenance. An interesting study by Pavlou et al. (113) showed a strong effect of exercise in the maintenance period on the ability to maintain the weight loss, as shown in Fig. 56.2 (113). Those individuals who maintained an exercise regimen maintained their weight loss, whereas those who abandoned the exercise regained their weight. Also, a number of carefully conducted studies have reported the superiority of adding exercise to diet (112,114,115). Although Miller et al. (116) in a metanalysis could find little difference in adding exercise to diet, Wing, reviewing six studies, reported that two of the six showed a greater weight loss with the addition of exercise, whereas four did not (112). More studies are needed on the amount of exercise required for maintenance. Schoeller et al. (117) calculated that an amount of exercise adding up to 47 kilojoules per kg of body weight per day would maintain weight. Data are available from the National Weight Loss Registry, a registry of persons who have lost at least 25 pounds of their weight and kept it off for 5 years. In order to maintain their weight loss, these individuals expend at least 400 kcal per day in physical activity (118).
The mechanics of getting sedentary, obese people to exercise are important. The program should start slowly. Attention should always be placed on adverse effects. In type 2 diabetic patients, particular care must be taken in evaluating potential coronary artery disease, peripheral vascular disease, and peripheral neuropathy. If the patient has known or suspected coronary artery disease, an electrocardiogram should be done. Exercise testing may also be indicated. People should begin with a walking program, which is gradually increased in intensity and duration. Some patients may then be able to move on to jogging, biking, aerobic dance, or resistance training. Others may never go beyond just walking. Patients need to be checked and check themselves regularly for intertrigo, dependent edema, foot or joint injuries, and blisters.
Figure 56.2. The addition or removal of learned exercise would appear to be a major contributing factor relative to weight maintenance. Subjects who ceased exercise regained or demonstrated a strong tendency to return to prestudy weights. Poststudy introduction of exercise (learned but not supervised) creates a positive effect. [From
Pavlou KN, Krey S, Steffee WP. Exercise as an adjunct to weight loss and maintenance in moderately obese subjects. Am J Clin Nutr 1989;49(5 suppl):1115–1123
, with permission.]
It is important to set duration and frequency goals for exercise. Usually, these begin with 30 minutes 5 days per week. This can be done in one bout or in separate bouts. Gradually, the time should be increased to 45 to 60 minutes and should be done each day. Other activities that a patient may prefer can be substituted for walking, such as rowing, biking, or swimming. Table 56.6 (119) gives approximate energy expenditure of different activities.
It is important to remember that as a person loses weight, the energy expenditure for a given activity will go down, because less weight is being carried about (98,99,100,120). As a result, the exercise goal has to be increased as weight is lost. This can be done by gradually increasing intensity or duration or both.
There have been a number of studies that have documented that long-term weight loss is associated with increased physical activity (121,122,123). For maintenance, therefore, there is good evidence that exercise will contribute to success.
Pharmacotherapy
Because weight loss and maintenance is so difficult, drug therapy is of great interest to patient and physician alike. The interest in drug therapy has been fanned by the new understanding that obesity is a chronic disease with genetic underpinnings (124,125,126) and that it requires chronic treatment. Thus, the idea that drug therapy is a short-term adjunct to diet and exercise has given way to the realization that drug therapy needs to be prolonged if not lifelong, much as drug therapy is used for diabetes, hypertension, and dyslipidemia.
It is important to stress that drugs for weight loss must always be given in conjunction with a program for diet and exercise (13). The inclusion of lifestyle modification in a program using drug therapy for weight loss leads to significantly greater weight loss and weight maintenance (127).
Two drugs have been approved for long-term use in obesity in the United States: sibutramine and orlistat. A third drug, phentermine, is also widely used long-term. There are also a number of drugs only approved for short-term use. The U.S.
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Food and Drug Administration (FDA) has established criteria for the use of the drugs. A guide for selecting treatment is presented in Table 56.7 (16). Drugs can be used for weight loss or weight maintenance in patients with a BMI greater than 30 and in patients with a BMI greater than 27 with two or more comorbidities (16).
Table 56.6. Approximate energy expenditure in selected activities for people of different weights
  Energy expenditure in kilocalories per 30 min for weight of
Activity 110 lb 130 lb 150 lb 170 lb 190 lb 210 lb
Aerobic dancing
   Walking pace 99 114 132 150 168 186
   Jogging pace 159 186 213 243 270 300
   Running pace 204 240 276 315 351 387
Basketball 207 243 282 318 357 396
Canoeing (leisure) 66 78 90 102 114 126
Canoeing (racing) 156 183 210 237 267 294
Carpentry 78 93 105 120 135 147
Cycling (5.5 mph) 96 114 132 147 165 183
Cycling (9.4 mph) 150 170 204 231 258 285
Dancing (ballroom) 78 90 105 117 132 144
Dancing (disco) 156 183 210 237 267 294
Gardening 150 177 204 231 258 285
Golf 129 150 174 195 219 243
Judo 294 345 399 450 504 558
Lying or sitting down 33 39 45 51 57 63
Mopping floor 96 105 120 138 153 171
Running
   11.5 min/mile 204 240 276 315 351 387
   9 min/mile 291 342 393 447 498 552
   7 min/mile 366 417 468 522 573 624
   5.5 min/mile 435 513 591 669 747 828
Skiing (cross-country) 216 252 291 330 369 408
Standing quietly 39 45 51 57 66 72
Swimming
   Backstroke 255 300 345 390 435 486
   Crawl 192 228 261 297 330 366
Table tennis 102 120 138 156 174 195
Tennis 165 192 222 252 282 312
Walking
   3 mph 102 114 126 138 153 165
   4 mph 120 141 162 186 207 228
Adapted from Gutin B, Kessler G. The high energy factor. New York: Random House, 1983, with permission.
Sibutramine
Sibutramine inhibits the reuptake of dopamine, norepinephrine, and serotonin at neural synapses in the central nervous system. Because both norepinephrine and serotonin play a role in food intake regulation, this drug targets two differing systems, the adrenergic and the serotoninergic. Six-month (128) and two-year (129) randomized clinical trials have been conducted that show a significantly greater effect of drug as compared with placebo (128,130). At 6 months the difference is a 5% to 8% loss for drug versus a 1% to 4% loss for placebo (128) (Fig. 56.3). It has also been tested in type 2 diabetes patients and found to be effective, although less so than in nondiabetic patients (131,132). A study in which an initial formula diet and sibutramine was used for 6 months and then randomization to either placebo or sibutramine for another 18 months showed excellent maintenance of weight loss for a period of 2 years (133) (Fig. 56.4).
Table 56.7. A guide to selecting treatment
Treatment BMI category
25–26.9 27–29.9 30–34.9 35–39.9 ≥40
Diet, physical activity, and behavior therapy With comorbidities With comorbidities + + +
Pharmacotherapy   With comorbidities + + +
Surgery       With comorbidities  
Prevention of weight gain with lifestyle therapy is indicated in any patient with a BMI ≥25 kg/m2, even without comorbidities, whereas weight loss is not necessarily recommended for those with a BMI of 25–29.9 kg/m2 or a high waist circumference, unless they have two or more comorbidities.
Combined therapy with a low-calorie diet, increased physical activity, and behavior therapy provide the most successful intervention for weight loss and weight maintenance.
Consider pharmacotherapy only if a patient has not lost 1 pound per week after 6 months of combined lifestyle therapy.
+, use of indicated treatment regardless of comorbidities.
Figure 56.3. Effect of sibutramine on body weight: a dose-ranging study. (From
Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999;7:189–198
, with permission.)
Figure 56.4. Effect of sibutramine, a randomized trial. Mean body weight changes during weight-loss and weight-maintenance phases. (From
James WPT, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trail. STORM study group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 2000;356:2119–2125
, with permission.)
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Because of its effect on the adrenergic system, sibutramine also affects blood pressure and heart rate (134). As a result, for a given level of weight loss there is not the corresponding decrease in blood pressure and heart rate that would be expected (128). In addition, some patients get an actual elevation of these and the drug must be stopped. Therefore, careful monitoring of this drug is necessary, especially early on after it has been introduced. The drug improves other comorbidities of obesity, such as dyslipidemia, uric acid levels, and glycemia in diabetic patients (130,131,132,133,135). Dosage begins at 10 mg once a day and may go to 15 mg. There is no evidence of any heart valve abnormalities with use of the drug (134,136). Side effects of the drug include dry mouth, headache, insomnia, and constipation.
Orlistat
Orlistat has a totally different mechanism of action from the usual central nervous system drugs. It works in the gut, inhibiting
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the hydrolysis of ingested fat and partially preventing its absorption by blocking the intestinal lipase from coming into contact with the fat. As a result, it blocks about one third of ingested fat from being absorbed (137). Randomized clinical trials of up to 2 years duration have been reported (138,139). At 1 year weight loss was 10.2% with drug and 6.1% with placebo (138). At 2 years the loss was 7.6% versus 4.5% (138). This is shown in Fig. 56.5 (139). It has also been tried in type 2 diabetic patients with some success, as demonstrated in Fig. 56.6 (140). Because steatorrhea with the drug will depend on the amount of fat ingested, it is important not to exceed 100 g or 35% of total calories as fat, so as not to experience undesirable side effects (diarrhea, frequency, oily spotting). The gastrointestinal effects are generally not too severe and improve over time. Because there is an independent effect on fat absorption, this drug lowers cholesterol more than would be predicted from weight loss (141). Levels of fat-soluble vitamins decrease as orlistat continues to be taken, although not to abnormally low levels (142). For precaution, a daily fat-soluble vitamin supplement should be given. Orlistat needs to be taken at the start of a meal to have the appropriate effect on intestinal lipase. The dosage is 120 mg three times a day before meals.
Figure 56.5. Effect of orlistat, a randomized trial. Mean body weight changes during weight-loss and weight-maintenance periods. (From
Sjöström L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients: European Multicentre Orlistat Study Group. Lancet 1998;352:167–172
, with permission.)
Figure 56.6. Randomized double-blind study of orlistat versus placebo in obese patients with type 2 diabetes. Frequency distribution of percentage change from initial body weight to end of 1 year. [From
Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care 1998; 21(8):1288–1294
, with permission.]
Phentermine
There are other anorectic drugs that have been approved for short-term use in the United States. These all act on the central nervous system either affecting noradrenergic or serotoninergic systems. One of these drugs is being used extensively long-term in the United States. It is an adrenergic drug. There have been two longer-term trials with this drug (143,144). One was conducted for 36 weeks, as a randomized controlled trial, with the
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drug arm being given drug continuously or intermittently every other week (143). Weight was similar in the two drug arms. Drugs yielded a 20.5% weight loss, whereas placebo gave a 6% loss. Figure 56.7 (143) shows the weight loss obtained. A second randomized trial of 6 months duration reported a weight loss of 12.6% in the drug arm and 9.2% in the placebo arm (144).
Figure 56.7. Effect of phentermine in obese patients given continuously or for 4 weeks on and off, compared with placebo, over 36 weeks in a double-blind trial. (From
Munro JF, MacCuish AC, Wilson EM, et al. Comparison of continuous and intermittent anorectic therapy in obesity. BMJ 1968;1:352–354
, with permission.)
Phentermine was one half of the phentermine-fenfluramine combination that was effective in eliciting weight loss but which had the severe adverse side effects of heart valve abnormalities and pulmonary fibrosis (145,146,147). Although the FDA banned fenfluramine, there was no evidence to implicate phentermine (146), and it has stayed in the market. No other long-term trials have been conducted, although no evidence of long-term toxicity has been reported. If this drug is to be used long-term, the physician should obtain a signed informed consent form from the patient.
Combination of Drugs
There have been few randomized controlled studies of the combination of sibutramine and orlistat. Wadden et al. (148) reported on one that added orlistat to the regimen after 1 year of sibutramine treatment when patients’ weights had plateaued. No further weight gain was documented.
Other Drugs
A number of other drugs have been approved for short-term use in the United States. These drugs have only been tested for safety and efficacy for a period of 12 weeks. They include amphetamine, benzphetamine, phendimetrazine, metamphetamine, and diethylpropion, and are all listed in Table 56.8 (149). Amphetamine and metamphetamine are DEA schedule II and therefore not used for weight loss any longer. Benzphetamine and phendimetrazine are DEA schedule III and must be used with caution. Diethylpropion and phentermine are schedule IV and used widely for weight control because abuse of these drugs is rare.
More recently, bupropion, an atypical antidepressant that is a weak norepinephrine, dopamine, and serotonin reuptake inhibitor, has been reported in a randomized clinical trial of 48 weeks to yield a 4.9% weight loss in comparison with a 1.3% weight loss for placebo (150,151). Topiramate, an antiepileptic drug, has also been shown to have weight loss properties (152,153) and has been used off-label by some physicians. Adverse effects of the drug include renal stones, fatigue, dizziness, somnolence, and possible cognitive dysfunction (154). Metformin has been used in type 2 diabetic patients, not only for glucose control but also to prevent weight gain. The effectiveness of metformin in this regard has been reported in the UKPDS (155). It must be remembered, however, that metformin is contraindicated in patients with renal insufficiency, congestive heart failure, or pulmonary or liver disease because of the possibility of initiating lactic acidosis.
Herbal Preparations and Dietary Supplements
The use of a combination of ephedrine and caffeine is common in Europe and has been tested in randomized controlled 6-month trials (133,156,157). A combination of ephedrine, caffeine, and aspirin has also been tested (158). Both these combinations have been found to be more effective than placebo. However, the use of ephedrine is not approved in the United States.
Of the herbal products, the only 6-month randomized clinical trial is by Boozer et al. (159), which tested herbal ephedra/caffeine versus placebo. There was modest but greater weight loss with the placebo. Blood pressure was not lowered to the extent expected given the weight loss. At the moment, there are insufficient data to recommend any herbal preparation as safe or effective (160).
In the past, practitioners have used digitalis, thyroid preparations, and diuretics as adjuncts for weight loss therapy. These should not be used. Also, inhibitors of carbohydrate absorption, such as α-amylase, α-glucosidase, and sucrase inhibitors, are not effective as weight loss agents.
Behavior Therapy
The use of behavior therapy for weight control goes back to Ferster et al. (161) and Stuart (162) in the 1960s. The original
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premise of behavior therapy was that eating in obese patients is maladaptive and that this can be changed for the better. More recently, as the etiology of obesity has been recognized as being affected by much more than maladaptive eating, especially genetic, environmental, and social factors, the attempt at behavior change has broadened to include changes in physical activity, the environment, and the social setting of an individual attempting to lose weight (163,164,165). Over the years, refinements of behavioral therapy techniques have been proposed (166,167,168,169,170).
Table 56.8. Appetite suppressant medications approved by the FDA for short-term use
Drug DEA schedule Trade name Dosage form (mg) Administration
Methamphetamine II Desoyn 5, 10, 15 10 or 15 mg in morning
   Amphetamine II Dexedrine 5, 10, 15 5 mg 2 or 3 times daily
   Benzphetamine III Didrex 25–50 Initial dose: 25 mg once daily
Maximum dose: 25–50 mg 3 times daily
   Phendimetrazine III Standard release:
  • Bontril PDM
  • Plegine
  • X-Trozone
Slow release:
  • Bontril
  • Prelu-2
  • X-Trozine
 35 35 mg before meals 3 times daily
Diethylpropion IV Tenuate 25, 75 25 mg three times daily
Dospan 75 mg once daily
Phentermine IV Standard:
  • Adipex-P
  • Fastin
  • Obenix
  • Oby-Cap
  • Oby-Trim
  • Zantryl
 37.5
30
37.5
30
30
30		 37.5 mg in the morning
30 mg/day 2 h after breakfast
37.5 mg/dy 9 a.m.
30 mg/dy 2 h after breakfast
30 mg/dy 2 hr after breakfast
30 mg/dy 2 hr after breakfast
Slow release:
  • Ionamin
 15, 30 15 mg/dy before breakfast (30 mg for less responsive patients)
Mazindol IV Sanorex 1, 2 Initial dose: 1 mg once a day
Maximum dose: 1 mg 3 times a day with meals
Mazanor 1 Initial dose: 1 mg once a day
Maximum dose: 1 mg 3 times a day with meals
FDA, U.S. Food and Drug Administration; DEA, Drug Enforcement Administration.
The aim of behavioral therapy is to change behavior by means of small, achievable steps. Because the behavior change will focus on diet and exercise, a modicum of knowledge about both of these is a necessary component of the therapy. Nutrition knowledge requires becoming familiar with caloric content of foods, energy density, portion sizes, cooking techniques, and selection of foods from the various food groups. Knowledge about physical activity requires understanding one’s own capabilities and limitations, physical disabilities, and understanding of the increased caloric expenditure created by different activities, their intensity, and duration.
Behavioral therapy begins with an initial assessment of the patient with regard to motivation, past history of weight loss trials, social and family background, and environmental conditions. It is important to individualize behavioral therapy to a particular patient’s situation. One of the important aspects of behavioral therapy is to set concrete, realistic, and attainable goals for changing behavior. These include goals for amount of weight loss, physical activity, and changes in patterns of behavior.
Specific behavioral strategies include the following: self-monitoring, stress management, stimulus control, problem solving, contingency management, cognitive restructuring, and social support (16). Self-monitoring has been found to be extremely important in weight control. It consists of observing and recording faithfully and as truthfully as possible various aspects of behavior, such as food intake, physical activity, and medication use. The importance of this is attested to by the fact that in the National Weight Loss Registry of individuals who
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have lost a significant amount of weight and kept it off for 5 years or longer, self-monitoring is considered the most important component of behavior change (171). It is important because it makes individuals conscious of exactly what they are doing with regard to the crucial behaviors that drive weight regulation.
Stimulus control is working at identifying what social or environmental cues lead to undesirable behavior. Once identified, a sustained effort is made to eliminate, change, or avoid these cues. This again requires self-examination by the patient with the help of the counselor. It requires honest confrontation with people and situations that cause excess eating. Stimulus control is closely tied to stress management. Stress may be free floating or brought on by specific situations and circumstances. Learning to identify these and trying to change or avoid them is an important aim of behavior modification.
Contingency management involves the application of rewards for moving to appropriate behavioral patterns for weight loss and maintenance. Behavior therapy stresses that a component of the therapy should be reward. This is based on the premise that weight control is difficult and that reinforcement of constructive behavior can lead to patient satisfaction and continued motivation. This is done by exploring the kinds of rewards a patient would find positive and pleasurable (a movie, a new CD, some jewelry, a book, etc.). This contingency management is often done with the use of contracts, whereby the patient agrees to modify a certain behavior (increase exercise bouts, decrease alcohol, decrease fried foods, etc.) in return for which a reward is negotiated.
Problem solving is individually based. A patient needs to identify particular problems that affect eating and exercise behavior and formulate strategies for reversing these. This can be related to particular types of foods that are a problem, particular cooking techniques, portion sizes, snacking, caloric beverages, and so forth. Also, particular situations or people may be involved. Each must be confronted in turn and reversed. It is important not to try to change all identified problems at once, but to take them one at a time.
Cognitive restructuring is aimed at altering inappropriate cognition that affects eating and activity behavior. Because individuals develop behavior patterns primarily through cognitive processes, it is necessary to identify these and attempt to change maladaptive ones. These include coping skills strategies and problem-solving strategies (172).
Social support can be very helpful in achieving success. It is for this reason that group therapy has been the method of choice to deliver behavior therapy. Peers can help to establish appropriate and realistic intragroup norms for eating and exercise. They can help counter the pressure of the outside world to see obese persons as unsuccessful if they do not reach ideal weight. Thinking patterns need to be diverted away from self-rejection toward self-acceptance (173).
Relapse prevention is an important component of behavioral therapy. The major problem with all treatments for obesity is a slow return to baseline weight after the treatment intervention ends (174). By 5 years after the start of a treatment program, most patients are back to baseline or beyond (174). Relapse prevention training aims at teaching how to avoid or cope with slips and slides backward (175,176). Continuing treatment beyond 6 months improves the maintenance of weight loss. Contact may be by actual group sessions, individual sessions, telephone calls, postcards, mailings, or Internet dialogue. These have been found to enhance weight maintenance (175). Providing a locale for continued peer support group sessions has also proven helpful (177).
A positive effect of behavior therapy is giving patients the major responsibility for the weight loss strategy so that with success, they can attribute increased power to themselves. This reinforces their motivation, increases their confidence, and is important in producing the will to maintain the effort over a long period of time.
For continuing success, the patient should remain in treatment not just until goal weight is achieved, but much beyond this.
Surgery
The number of persons who are severely obese continues to increase in the United States. Many of these persons have tried repeatedly to lose weight and failed. More and more of them are turning to surgery to try to reverse their condition. At the moment, individuals being considered as appropriate for surgery include those with a BMI of 40 or above without other associated health problems and those with a BMI of 35 or above with comorbid conditions (178).
A number of different procedures are now being performed for obesity: gastric banding, vertical banded gastroplasty, gastric bypass, and ileopancreatic bypass. The different procedures are depicted in Fig. 56.8 (179). Two procedures, gastric banding and vertical banded gastroplasty, are essentially restrictive; that is, they prevent too much ingestion. Two, gastric bypass and biliopancreatic bypass, are primarily malabsorptive. Gastric banding (180) is usually performed laparoscopically. A band is placed around the upper end of the stomach that creates a small reservoir of 35 to 50 mL and a small passageway to the rest of the stomach. Vertical banded gastroplasty (181) consists of stapling the stomach vertically and creating a similar reservoir as in gastric banding and a passageway about 1 cm in diameter to the rest of the stomach. Gastric bypass (182) is a more complex operation in which a small reservoir is created at the upper end of the stomach and a loop of small bowel is brought up and anastomosed to it in a Roux-en-Y procedure. Biliopancreatic bypass (183) requires transection of the stomach, with drainage to the lower jejunum or ileum. The duodenal contents are then emptied into the jejunum or ileum at a variable distance from the ileocecal valve. The weight loss varies from patient to patient but tends to continue for 12 to 18 months and then plateaus off. Some patients then regain. In general, weight loss is least for banding, next for vertical-banded gastroplasty, next for gastric bypass, and most for ileopancreatic transposition. Biliopancreatic bypass is not commonly performed in the United States because it has significantly more adverse side effects. These include severe diarrhea and liver disease (184). Figure 56.9 (185)
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shows the weight loss with the two procedures most frequently done. The longest study of the effects of obesity surgery is the Swedish Obesity Surgery study (SOS) (186). In this study, weight loss was 23% ± 10% of excess weight in 2 years with vertical banded gastroplasty and 33% ± 10% with gastric bypass (187). Although gastric bypass produces greater weight loss, it also produces greater operative and postoperative mortality and more long-term side effects. The 8-year follow-up report of the SOS has shown that in the operated patients, although lipids have remained improved and development of type 2 diabetes has been prevented, blood pressure has returned to its preoperative levels (188).
Figure 56.8. A: Vertical-banded gastroplasty. B: Roux-en-Y gastric bypass. (From
Flancbaum L. The doctor’s guide to weight loss surgery. West Hurley, NY: Fredonia Communications, 2001
, with permission.)
Conclusion
Obesity is never really cured, it is only contained. Weight loss is difficult and requires a sustained effort by both the patient and the physician. Often, other health professionals do better at assuming the treatment responsibility for this condition. After weight loss, weight maintenance is a particularly difficult task and requires continued contact between patient and health-care provider. In patients with a family history of type 2 diabetes, it is important to focus on prevention of weight gain because obesity is a major risk factor for increasing insulin resistance, placing a stress on the β-cells of the pancreas. This can lead to the development of diabetes. In patients who already have diabetes and are obese, weight loss will improve glucose control.
Figure 56.9. Weight loss after vertical-banded gastroplasty and Roux-en-Y gastric bypass. [From
Sugerman HJ, Kellum JM, Engle KM, et al. Gastric bypass for treating severe obesity. Am J Clin Nutr 1992;55(2 suppl):560–566
, with permission.]
Acknowledgments
I acknowledge the support of the National Institutes of Health through Grants DK-26687 and DK-40414. I also thank Brian Dauth for his editorial assistance.
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