Weight-loss drug has dual benefits for type 2s. (In the Pipeline) Diabetes Forecast v51, n11 (Nov 1998): 35 (3 pages).

COPYRIGHT 1998 American Diabetes Association Inc.

Orlistat (Xenical), a weight-loss drug pending approval by the Food and Drug Administration, has been shown to have not one but two major benefits for obese people with type 2 diabetes In a 57-week multi-center study of obese patients with type 2, researchers observed greater weight loss and better glycemic control in patients who took orlistat compared with those who took a placebo (a pill containing no active ingredients).

Of the 254 patients who completed the study, 138 took orlistat and 116 took a placebo. All 254 followed a diet slightly reduced in calories to help them lose weight, and all were controlling their diabetes well with sulfonylurea drugs when the study began.

The difference in weight loss between the two groups became apparent only four weeks into the study. Those who took orlistat lost weight at a faster rate than those who took the placebo. At the end of the study, the orlistat group had lost an average of 13 pounds, compared with an average of 9.5 pounds in the placebo group. The orlistat group also attained lower levels of fasting glucose than the placebo group. As a result, the average dose of sulfonylurea medication decreased more in the orlistat group than in the placebo group. In the orlistat group, 43 percent of the participants decreased the amount of oral sulfonylureas they took, and 12 percent were able to discontinue oral sulfonylureas entirely. In the placebo group, only 29 percent were able to decrease their oral sulfonylurea dose. The researchers believe that the better glycemic control in the orlistat group stems from that group's greater weight loss; weight loss has been shown to improve glycemic control. The orlistat group also had improved serum lipids, with better levels of total cholesterol, lower levels of low-density lipoprotein (LDL, or "bad") cholesterol, and lower levels of triglycerides.

Orlistat belongs to a new class of drugs called lipase inhibitors.Instead of reducing appetite as many diet drugs do, orlistat and the other drugs in its class reduce the amount of dietary fat absorbed in the intestines. If the fat is not absorbed, it will not get into the bloodstream to affect lipid and cholesterol levels. Orlistat is not without side effects, however. The unabsorbed fat passes through the intestines, which can result in gastrointestinal effects ranging from oily stools to fecal incontinence. Moreover, because the fat is not absorbed, fat-soluble vitamins like vitamin E and beta-carotene are not broken down and made readily available for use in the body. The orlistat group did experience a decrease in vitamin E and betacarotene absorption during the study, but the decrease was offset by vitamin supplements.

Hoffmann-LaRoche, which makes orlistat, funded the study. The company expects to fulfill the requirements for final FDA approval during the first quarter of 1999.

Aronne, Louis J. Modern medical management of obesity: the role of pharmaceutical intervention.

Journal of the American Dietetic Association v98 n10 (Oct, 1998):S23 (4 pages).

COPYRIGHT 1998 American Dietetic Association

The medical treatment of obesity has been a topic of controversy for many years.

The popularity, and overuse, of the combination of medications phentermine and fenfluramine (phen-fen), combined with the introduction of several new medications and withdrawal of others has fueled the fire. Rapid advances in our understanding of the weight-regulating mechanisms make it likely that in 10 or 20 years the use of medication will be as standard in the treatment of obesity as the use of medication is now in the treatment of hypertension, diabetes, or hyperlipidemia. In fact, the treatment of obesity could supplant the treatment of many of the comorbidities of obesity, on which Americans currently spend billions of dollars per year. Medication will be used in conjunction with behavior, diet, and exercise programs as part of a standard regimen of treatment. No single component of treatment will dominate this regimen, but it will be common for all components to be used to varying degrees in different patients.

OBESITY AS A CHRONIC DISEASE

When considering the current medical treatment model, it is important to emphasize that obesity is a lifelong chronic disease that has responded poorly to behavioral management. Indeed, guidelines from the National Institutes of Health and the National Heart, Lung, and Blood Institute (1; see page 1177 of the October Journal for the Executive Summary of this report) will recommend that obesity be considered and managed as a chronic illness. Short-term or intermittent treatment like that used for patients with asthma may work in some patients, but for many with serious obesity, the problem needs to be viewed more like hypertension or diabetes. Many patients with adult onset type 2 diabetes, for example, are treated with medication on a daily basis. If patients stop taking their medication, the physician or Certified Diabetes Educator asks why they are not complying; the regular use of the medication is expected, even though many patients with diabetes could probably manage their blood glucose level by watching their diet more carefully and exercising more frequently. Obesity, which is believed to cause most cases of diabetes, should be regarded in the same way. In the case of an obese person with adult onset type 2 diabetes, if the addition of medication to treat the obesity also treats the diabetes, chronic treatment of the obesity makes sense. A different treatment model is the example of a patient with asthma who may take 2 medications for a few weeks and then taper down to I medicine, but the asthma may subsequently worsen and require the strongest treatment, corticosteroids. Similarly, for some obese patients, as willpower, stress, physical activity, and other factors wax and wane, the optimal treatment of their disorder may require intermittent, rather than continuous, treatment with medications.

Short-term solutions have proven ineffective in the long-term management of obesity, and they simply do not exist in the chronic disease treatment model any more than a simple cure for hypertension exists. A long-term approach to managing obesity is needed, because the disease will recur after the treatment is withdrawn or if the patient does not follow the treatment plan. This treatment failure should not be considered the patient's fault. It is clear that there are powerful physiologic mechanisms that drive weight back up following weight loss (2). The regulation of body weight is complex and only partially understood. Body weight seems to be regulated in much the same way that blood glucose levels, blood pressure, and body temperature are regulated; the mechanisms appear to be complex and to involve redundant feedback loops and other mechanisms that are not yet clearly understood.

THE PHYSIOLOGY OF WEIGHT CONTROL

The challenge of managing obesity will continue to perplex health care professionals until the body's weight-control mechanism is better understood. Why do people only lose 10% or 15% of their body weight? A possible answer may be illustrated with a simplified feedback loop based on information taken from animal studies (Figure). As weight is lost by reducing food intake, which involves the efferent portion of the weight-control feedback loop (ie, between the brain and its effect on the fat cell), the fat cells shrink, reducing expression of the ob gene and its hormone product, leptin. As a result of the decrease in leptin levels in the blood and brain, metabolic rate decreases, appetite increases, and other hormonal changes associated with weight loss are observed. Replacing leptin to achieve original levels of leptin does not completely normalize appetite and prevent weight regain in animals, however, suggesting that other hormones or neuropeptides are involved in this feedback mechanism. The net result is that weight loss ceases at a weight for which the effect of the leptin replacement is counterbalanced by an increase in appetite and a reduction in metabolic rate induced by the shrinking fat cell.

If this hypothesis, which illustrates only part of the mechanism found thus far in animals, is correct and applies to human beings as well, the concept of a weight plateau makes perfect sense. Until scientists can intervene at the level of the afferent limb of the weight-control feedback loop (between the fat cell and its hormonal effect on the brain), a body weight loss of 5% to 15% may be the best, on average, that can be achieved before adaptive counterregulatory systems are activated to an extent that results in weight being regained. We should not, however, dismiss the benefits of modest weight loss: there is compelling evidence (1) that even a small amount of weight loss, as little as 5%, is associated with significant improvements in health status. At present, the criteria for success in weight management, given the tools currently available, is to achieve and maintain even small weight loss (3).

PHARMACOLOGIC TREATMENTS FOR OBESITY

Until September 1997, the combination of phentermine and fenfluramine (phen-fen) was the most popular treatment for obesity. The rationale behind it was reasonable: a low-dose combination of drugs affecting different central nervous system mechanisms could be clinically effective with fewer adverse effects than either drug alone at higher doses. Results in a small number of uncomplicated patients treated with phentermine and fenfluramine demonstrated that together they were the most successful medical treatment for obesity yet devised, and in some persons the combination helped maintain weight loss for up to 4 years.

Unfortunately, fenfluramine (Pondimin) and dexfenfluramine (Redux) have been associated with the development of primary pulmonary hypertension and a valvular heart disease characterized by mild aortic regurgitation, moderate mitral regurgitation, or both (4). Other pathologic manifestations have been described (5), including a thickening of the cardiac valves with an exudate similar to that seen in carcinoid syndrome, in which blood serotonin levels are elevated. As a result, fenfluramine and dexfenfluramine have been withdrawn from the market. The mechanism by which these serotonin-releasing agents might cause valvular damage is not understood.

New options for the pharmacologic treatment of obesity are available, and more will continue to be introduced. Sibutramine (Meridia) is a serotonin and norepinephrine reuptake inhibitor. It is similar in certain ways to the selective serotonin reuptake inhibitors that have been available for more than 10 years for the treatment of depression. Orlistat (Xenical) is a gastrointestinal lipase inhibitor that works by a novel mechanism of action (6). It is nonsystemic, has no central nervous system effects, and does not affect appetite. Rather, orlistat reduces the absorption of dietary fat by roughly 30% by inhibiting gastrointestinal lipase activity.

Medication should only be considered for patients with a body mass index (BMI) greater than 30, or greater than 27 if they have 2 or more comorbidities and have failed to lose weight on a program of diet, exercise, and behavior therapy (1).

Sibutramine

Sibutramine is the first reuptake inhibitor to have been approved as an appetite suppressant. Sibutramine reduces appetite, enhances satiety and, in animals, increases metabolic rate. It has fewer and less severe side effects than older appetite suppressants, which work by causing norepinephrine release. The metabolic studies performed thus far on human beings are not definitive about the effect of sibutramine on energy expenditure, although in animal studies that effect is clear (7). Sibutramine proved ineffective for its original purpose as an antidepressant (8), although it was noted in these early trials that patients lost weight while taking it. Sibutramine is similar to venlafaxine (Effexor) in its mechanism of action (9), although it has a greater effect on norepinephrine and a smaller effect on serotonin than does venlafaxine.

Studies lasting as long as 1 year have been conducted to examine the effect of sibutramine on weight loss (8,9). In a study of patients with a starting body mass index (BMI, measured as kg/[m.sup.2]) of 33, a daily dose of 10 mg sibutramine resulted in a mean weight loss of 4.8 kg, and a 15-mg daily dose resulted in a mean weight loss of 6.1 kg, whereas patients receiving a placebo lost a mean of 1.8 kg. Body weight reached a plateau after about 6 months (8,9). A categorical, or responder, analysis of the efficacy of sibutramine in this study looked at those patients receiving sibutramine for 1 year who achieved [greater than] 5% or [greater than]10% weight loss. Of patients involved in the study for 1 year 29% of those in the placebo group achieved [greater than] 5% weight loss, compared with 56% of those in the sibutramine group receiving a daily dose of 10 mg, and 66% of those in the sibutramine group receiving a daily dose of 15 mg. On the other hand, weight loss [greater than] 10% of initial weight was achieved by 6% in the placebo group, 30% in the sibutramine at 10 mg group and 39% in the sibutramine at 15 mg group (10).

The most common adverse effects of sibutramine include constipation, dry mouth, headache, and insomnia. Sibutramine may also increase blood pressure and heart rate. The average increase in blood pressure is 4 mm Hg (9), and the more weight patients lose, the less likely they are to have an increase in blood pressure. However, 1 in 8 patients may have an increase in blood pressure of 15 mm Hg or greater, and blood pressure and pulse must be monitored regularly. Blood pressure returns to normal when the medication is stopped. Only 0.8% of patients had to be withdrawn from the clinical trials for either hypertension or tachycardia, compared with 0.5% in the placebo-treated group. Sibutramine must be used cautiously in patients with hypertension, and its use is not recommended in patients with coronary artery disease, arrhythmias, congestive heart failure, or stroke.

Orlistat

A promising antiobesity medication on the horizon is orlistat. Orlistat is a gastrointestinal lipase inhibitor that competes with dietary fat for sites on the lipase molecules in the gastrointestinal tract. Only trace amounts of orlistat are absorbed through the gastrointestinal tract, and orlistat has been shown to have no systemic effects. It blocks the absorption of about 30% of dietary fat at a therapeutic oral dose of 120 mg three times a day. It has no apparent effect on appetite.

In addition to preventing the absorption of fat, orlistat may enhance dietary compliance with a low-fat diet. It gives patients a strong gastrointestinal feedback message if they eat too much fat in their diet. In our clinical experience with this drug, some patients tested its efficacy by eating more fat than recommended. If they experienced side effects such as oily stools, they adjusted their dietary fat intake accordingly to prevent the side effects.

In a 1-year trial (11) of patients prescribed a dietitian-supervised low-fat, energy-restricted diet and either 120 mg orlistat 3 times a day or placebo, a mean weight loss of 9% was found in the patients who received orlistat vs a mean weight loss of 5.8% in the placebo group (P [less than].05). In a responder analysis, 33% of patients receiving placebo vs 55% of patients in the orlistat group lost more than 5% of their initial body weight. Fifteen percent of the patients in the placebo group vs 25% of patients in the orlistat group lost [greater than] 10% of their initial body weight.

HEALTH BENEFITS ASSOCIATED WITH MEDICAL MANAGEMENT

Weight loss is not the only goal of obesity treatment. Improvement in the comorbidities associated with obesity is an important endpoint in current clinical trials. With sibutramine, there is evidence that some of the comorbidities associated with obesity improve: metabolic parameters such as uric acid concentration, glucose levels, and lipid levels improve in direct relationship to the amount of weight lost (10,12).

In addition to the health benefits brought on by weight loss, orlistat induced a further 8% reduction in low-density lipoprotein cholesterol independent of weight loss. Other health improvements include decreased blood pressure, improved fasting insulin levels, and improved glycemic control in study patients with diabetes.(13).

An improvement in glucose tolerance status is among the most exciting findings of the orlistat clinical studies. In addition to helping patients comply with a low-fat weight loss diet, orlistat may help to improve impaired glucose tolerance and thus prevent diabetes. The pooled clinical data indicate that of patients whose initial oral glucose tolerance test results showed diabetes in the diet alone (placebo) condition, 15% improved to normal glucose tolerance and 15% improved to impaired glucose tolerance (14). In the patients who received orlistat, of those who tested positive for diabetes at baseline, 25% improved to normal, and 43% improved from diabetic to impaired glucose tolerance. Two thirds of patients receiving orlistat improved their glucose tolerance, compared to less than one third on diet alone, a strikingly better result with orlistat compared with placebo. This is a substantial improvement in health outcome, and in view of the economic burden of diabetes, this finding has important public health implications.

Of the patients who had impaired glucose tolerance at baseline, 10% of those receiving a placebo progressed to diabetes, while the glucose tolerance of only 2.6% of those receiving orlistat worsened, a 4-fold difference in outcome. Of the patients with impaired glucose tolerance at baseline, 46% of those in the placebo group and 72% of those receiving orlistat shifted to having normal glucose tolerance at 1 year.

The frequency of gastrointestinal side effects was 41% greater in those receiving orlistat than in the placebo group, although few patients dropped out as a result of side effects. Of interest, 82.3% of patients receiving orlistat completed 1-year trials, compared with only 75.1% of those receiving a placebo, suggesting that the gastrointestinal side effects of orlistat were not great enough to dissuade them from taking the drug. During the second year of the 2-year trials, the number of gastrointestinal side effects decreased substantially, so that there were only 17% more side effects in the patients receiving orlistat than in those receiving a placebo. In general, the gastrointestinal side effects were described as being mild to moderate, occurred early in treatment and resolved spontaneously. Our own personal experience, based on anecdotal evidence from patients, suggested that they tested the drug by eating a high-fat food to see what happened. If they experienced a gastrointestinal side effect, they would cut back on the portion size, or try a low-fat alternative. Patients learned how much fat they could tolerated while on the medication and kept their fat intake to a level slightly below this threshold. It is the consumption of excess dietary fat, not the drug, that triggers the gastrointestinal side effects. Thus, patient education will be crucial to prevent gastrointestinal side effects when prescribing a drug such as orlistat.

SUMMARY

In conclusion, obesity is an epidemic in our society. It is associated with at least 1 comorbidity in most patients with a BMI of 27 or greater. Dietitians, as well as physicians, play an integral role in the management of obesity. As better medical treatments for obesity become available, the focus in dietary prescription may shift away from reducing energy and fat intake toward healthier eating for disease prevention. A comprehensive approach, which, in some patients, may include medical therapy as an adjunct, is necessary to treat obesity effectively. Candidates for treatment with medication include patients with a BMI greater than 30, or greater than 27 if they have comorbidities. Antiobesity agents with novel mechanisms of action will supply

Drug Development Fat Blocker Anti-Obesity Drug Launched in United Kingdom.

World Disease Weekly Plus (Oct 5, 1998):NA.

Copyright 1998 Charles W Henderson

An anti-obesity drug that works by reducing fat absorption in the body was launched in Britain.

Doctors said a two-year clinical trial showed that Xenical, plus a reduced fat diet, helped obese people lose more than 10 percent of their body weight in one year.

"Xenical produces and maintains clinically significant weight loss," Dr. Nick Finer, a consultant endocrinologist, told a news conference to launch the treatment.

Unlike slimming pills that suppress the appetite, Swiss drugs giant Roche Holding' "fat blocker" drug is an approach to treating obesity, a condition that affects tens of millions of people worldwide.

Pencil, known generically as orlistat, works in the gut where it prevents absorption of 30 percent of dietary fat. Too much fat in the diet and lack of exercise are the main causes of obesity.

But doctors said that Xenical was not a wonder drug, or the Viagra for obesity, and would be available only on prescription for obese people who must take it with a reduced fat diet.

"Obesity is now being recognized as a medical problem. We are now being given the tools to do something useful about it," said Professor Gareth Williams, University of Liverpool, in northwest England. "We have to do this as part of a plan," he added.

People are prescribed the drug only if they are clinically obese and have lost 2.5kg(5.5 pounds) over four consecutive weeks on a special Medical Action Plan designed as part of the treatment.

Roche denied media reports that Xenical would cost Britain's government-funded National Health Service (NHS) 700 million pounds ($1.18 billion), more than Pfizer's impotence drug Viagra, if most of the nation's 7.5 million obese adults received it.

"We don't anticipated it being anywhere near the number," Vic Ackerman, Roche U.K., told reporters.

He added that the company expected that less than five percent of obese people in Britain would be eligible to receive Xenical.

In September 1998, Britain's Department of Health banned doctors from prescribing Viagra on the health service because of financial concerns. There are no restrictions on the obesity treatment, but the British Medical Association called for government guidelines on who should receive it.

Mulrow, Cynthia D.Helping an obese patient make informed choices. (Clinical Review) British Medical Journal v317, n7153 (July 25, 1998): 266 (2 pages).

Copyright 1998 British Medical Association (U.K.)

Not long ago, a patient, whom I will call Mrs. Bariatrico, asked me to prescribe a diet pill for her. Mrs. Bariatrico is a middle class woman aged 48 years. She is 1.6m tall and weighs 77.2 kg. Her body mass index is 30.2 and her waist to hip ratio is 1.0 Mrs. Bariatrico is healthy and does not smoke. She told me she plans to enroll in a commercial diet programme and believes her ability to change her lifestyle is good? Her main concern is cosmetic--she values "looking good" and considers weight loss an important outcome.

As her primary care provider, I had several concerns. I knew the health insurance system that serves Mrs. Bariatrico has no formal weight loss programmes, and the cost of appetite suppressing drugs in not reimbursed. I had some doubts about my own ability to manage obesity and asked the following questions:

Expected benefits and hazards

Randomised trials confirm several physiological benefits--including reductions in blood pressure and glucose and lipid concentrations--when weight is reduced by 10-15%. [2] Trials are neither large enough nor long enough to identify survival benefits.One observational study that lasted 12 years showed that an intentional weight loss of 0.5-9.0 kg in overweight women with disorders related to obesity was associated with a 20% reduction in all cause mortality (relative risk = 0.80; 0.68 to 0.94). [6] Potential hazards of weight loss include increased risks of gallstones during rapid weight loss and loss of bone density.[2]

Treatment options

A comprehensive systematic review from the Centre for Reviews and Dissemination evaluates treatment options appropriate for Mrs. Bariatrico.[7] These include diet, exercise, and appetite suppressing drugs.A recent book describes many complementary therapies, including herbal remedies and chromium, but none have been adequately evaluated in controlled trials?

Diet and exercise

Randomised controlled trials show that diets allowing an intake of 1200 kcal/day coupled with behavior modification result in an approximate weight loss of 8.5 kg at 20 weeks.[9] Providing patients with food and meal plans, focusing on restricting fat as well as calories, and encouraging daily self monitoring of weight may be particularly effective strategies.[7] Very low calorie diets of less than 800 kcal/day result in a weight loss of approximately 20 kg at 12 to 16 weeks. One half to two thirds of the weight loss is maintained at one year. [9] Adding regular aerobic exercise results in minimal additional weight loss (approximately 2.5 kg after six months) and limits the amount of weight regained.[10] Resistance exercise has little effect on weight but increases the lean body mass.[10]

Appetite suppressants

Double blind randomised trials of longer than six months' duration show that antidepressant serotenergic agents such as fluoxetine are not effective weight loss treatments.[7.11] Other serotonergic agents, dexfenfluramine and fenfluramine (a racemic mixture of D-fenfluramine and L-fenfluramine), are effective when combined with diet. [7.11] Five trials, in which 1029 patients participated, showed that the weight loss with dexfenfluramine was 2.5 to 8.7 kg greater than with placebo at six months; two trials showed losses of 2.6 and 4.2 kg at 12 months.[11] The combination of fenfluramine and phentermine (colloquially known as fen-phen) resulted in a loss of 9.7 kg after six months compared with placebo. The two drug are sibutramine (serotonin and noradrenergic reuptake inhibitor) and orlistat (a fat absorption inhibitor). In one multicentre randomised trial, sibutramine showed a 2.8 kg loss compared with placebo at 12 months.[7] In a preliminary report from one centre of a multicentre trial comparing orlistat with placebo, weight reduction with orlistat was 3.1 kg more than with placebo at six months.[12] Trial data beyond 12 months of active treatment are not available for either of the two agents, and effects on mortality are not known.

Adverse effects that occur in more than 10% of patients taking dexfenfluramine include tiredness, diarrhea, and dry mouth. Use of appetite suppressants (mostly dexfenfluramine) for more than three months is associated with pulmonary hypertension.[13] The risk is estimated at 23-46 cases per million per year or one in 22,000-44,000 patients taking appetite suppressing drugs. Highly publicized case series describe unusual heart valve deterioration in 60 otherwise healthy women taking newer agents.[1415] Most were taking the combination of fenfluramine and phentermine, but six were taking either fenfluramine or dexfenfluramine alone. [14 15] In addition, a case series of 291 asymptomatic people taking these drugs showed that 92 had evidence of valvular disease, primarily aortic regurgitation.[16] This information prompted manufacturers to withdraw dexfenfluramine and fenfluramine from the market in September 1997.

The informed decision

I gave Mrs. Bariatrico feedback on the health risks of obesity, listed the treatment options, and advised her about the expected effects. She viewed the health risks of obesity as relatively minor and reiterated her primary value of losing weight so she would "look and feel good." She was surprised that the weight loss expected from diet pills was not greater and worried about possible serious adverse heart effects. She was determined to try a low fat, low calorie diet and daily exercise. I praised her willing ness to tackle difficult lifestyle changes. On her way out the door, she turned, smiled at me, and requested a prescription for phentermine--one of the few remaining appetite suppressants available on the market.

Work Janis A.. Exercise for the overweight patient.Physician and Sportsmedicine v18, n7 (July, 1990): 113 (2 pages).

Exercise alone is not enough to achieve weight loss for an obese patient. The overweight patient must exercise to keep off the pounds lost through dieting. Exercise programs must involve a minimum of 20 to 30 minutes maintained at a conversational level (i.e. being able to maintain a conversation during exercise) and patients should exercise lasting one hour per session and performed three to fives times a week is recommended to burn calories and avoid injuries.

Exercise performed on a regular basis is as important as the duration and therefore walking three times a week or every day is highly recommended, since it is safe and can be performed anywhere. There is reduced risk of trauma and overuse injuries form swimming; however, patients may be self-conscious in a swimsuit and this type of exercise may not be a good first choice.

Cross country ski machines, stationary bicycles, and rowing machines may be used, and in fact, any form of activity is good so long as it is safe for the patient. Exercise for overweigh patients should involve total body motion of the use of large muscle groups. It is important to remember that the dropout rate from all exercise programs is high; statistics show that only 20 percent of those that start an exercise program continue it for one year. Exercise must become part of a patient's life and it may be a social event if the patient joins a gym or exercises with a friend. Patients should be encouraged to follow a routine in a health club before purchasing equipment and attempting to exercise at home. Physicians should motivate patients in order to achieve the benefits of exercise. The patient and the physician should plan a program that is realistic and includes activities that the patient will enjoy in order to achieve long lasting results. Physicians should communicate to the patient both the benefits of exercise and the health risks of not exercising.Some obese patients may have multiple musculoskeletal problems, and before initiating an exercise program it would be useful to encourage patients to simply become more active. Patients should avoid the use of television remote controls, they should walk instead of driving a car, and should climb stairs instead of using an elevator. Patients with health problems such as hypertension or diabetes, or those on very low caloric diets may require special considerations. Exercise is an important component of maintaining weight loss and should be a positive lifestyle change. (Consumer Summary produced by Reliance Medical Information, Inc.) 7.

Wadden, Thomas A.; Van Itallie, Theodore B.; Blackburn, George L. Responsible and irresponsible use of very-low-calorie diets in the treatment of obesity, JAMA, The Journal of the American Medical Association v263, nl (Jan 5, 1990):83 (2 pages).

Oprah Winfrey's experience of losing 67 lbs in only four months by the use of a medically supervised very-low-calorie diet used in the 1970s and were associated with a large number of deaths. In general these diets were used by individuals who were not under the care of a physician, and were dificient in protein and other essential vitamins and minerals. Athough the present version of very-low-calorie diets contains essential nutrients with high-quality protein, and are much safer than their predecessors, they should only be used by individuals who are severely obese and only when under strict medical supervision. These diets provide between 400 to 800 calories/day and are designed to cause the greatest weight loss possible without a significant effect on the lean (muscle) mass of the body. These diets provide between 45 to 100 grams per day of protein (30 grams equal to one ounce) which is contained in a powder derived from egg or milk products. The diet powder is stirred into water and consumed three to five times per day. In some forms of this diet portions of lean meat, fish or fowl are also included in the daily food intake. Dieters also take supplements of vitamins, minerals and drink at least 2 liters of water or non-caloric fluid per day. An average woman will lose approximately 1.5 kg/week and a man 2.0 kg/week (1 kilogram is equal 2.2 lbs). Patients in controlled experimental conditions have been kept on this type of diet for 12 to 16 weeks; this period of dieting is usually sufficient to produce satisfactory results. Following this phase of the diet the patient enters a refeeding period in which conventional foods are gradually introduced into the patient's diet. This is followed by a weight-maintenance period. Medical supervision is required for all three: weight loss, refeeding, and maintenance. Patients require weekly physician examinations and should have their electrolyte levels (level of ions such as sodium and potassium) checked at least every other week. The authors strongly advise that no modification from the above guidelines be taken as there are risks associated with irresponsible use of this method of dieting, particularly by individuals who are not grossly obese. Physicians wishing to use very-low-calorie diets within their practice are similarly warned that they must posses adequate knowledge and training concerning these diets.

Dietary Diversity and Body Fat. Harvard Women's Health Watch v6, n9 (May, 1999):HARV99141006.

COPYRIGHT 1999 President and Fellows of Harvard College

It may be the spice of life, but variety can also be the bane of weight control, according to a study published in the March 1999 issue of The American Journal of Clinical Nutrition. A team of nutritionists from Tufts University found that having a wide array of foods from which to choose is often an enticement to consume more calories than we need.

The Tufts researchers inspiration came from earlier studies in both laboratory animals and humans. Those investigations indicated that lab animals eat more and eat more often when the selection of foods is greater. Similarly, in single-meal experiments, men and women tended to eat more when there were several different items on their plate instead of a single item, regardless of portion size.

The researchers recruited 71 healthy men and women, ages 20 to 80 years old. All participants were weighed and measured and underwent a body-composition analysis. In addition, each one filled out a questionnaire in which they recorded the types of foods they consumed over a 6-month period.

The questionnaires listed as many as 20 types of food in each of eight major categories breakfast foods, lunch and dinner entrees, sweets, snacks, and carbohydrates, condiments, fruit, vegetables, calorie-containing beverages, dairy products. Breakfast-food condiments (i.e. cream, milk, and sugar) and beverage condiments (i.e. sugar, cream) were also included, lest any calories go unaccounted for. Variety in eating was calculated as a percentage of the total number of foods in a group. For example, participants who ate only two of the 10 types of fruit listed received a 20% variety score for that category. Each participants scores in each category were matched to the numbers of calories consumed and to their proportion of body fat.

The researchers determined that people who ate a wide variety from any category tended to consume a greater number of calories from that category. Moreover, consuming a large variety (and a large number of calories) from certain food categories sweets, snacks, condiments, entrees, and carbohydrates was linked to increased body fat. In contrast, participants who consumed a larger variety of vegetables and took a greater proportion of calories from vegetables tended to be thinner.

In many respects, the study provided a mirror of the real world. Since 1980, the introduction of new snack foods, bakery products, and entrees has far outpaced the arrival of new varieties of fruits and vegetables. At the same time, the percentage of the population considered obese has risen precipitously.

That two-decade interval has witnessed mounting evidence that a diet rich in green, leafy, and yellow vegetables offers protection against heart disease, cancer, and vision loss. That information alone should be reason enough to increase the array of vegetables we consume.

Apgar, Barbara Does Weight Loss Plus Exercise Improve Insulin Sensitivity?American Family Physician v59, n6 (March 15, 1999):1641 (1 pages).

COPYRIGHT 1999 American Academy of Family Physicians

Weight loss in obese persons is associated with a decrease in insulin resistance and postprandial glucose and insulin levels. It has been suggested that additional benefit may be derived by combining weight loss and exercise. Weinstock and associates investigated the effects of diet and exercise on weight loss and insulin sensitivity in 45 obese women without diabetes. The subjects were randomly assigned to one of three 48- week weight loss programs: diet alone; diet and aerobic training; and diet and strength training. All women participated in the same group behavior modification program and diet program. They consumed a diet of 925 calories per day for the first 16 weeks, followed by an increase to 1,500 calories per day for the remainder of the supervised diet and exercise program. Exercise consisted of three sessions per week for the first 28 weeks and two sessions per week for the next 20 weeks. Exercise was unsupervised during the remainder of the follow-up period. Twenty-two subjects were also evaluated approximately one year after the study (week 96).

To assess the effects of weight loss and exercise on insulin sensitivity, oral glucose tolerance tests were performed at baseline and at weeks 16, 24, 44 and 96. Subjects in all three groups lost weight during the first 16 weeks. At week 16, the mean weight loss was 13.8 kg (30.4 lb), and this weight loss was maintained through weeks 24 and 44. In the 22 subjects who returned for a final visit at week 96, weight had increased from the 44th week to the 96th week, resulting in a mean net weight loss of 9.9 kg (21.8 lb) from baseline weight. At week 44, these subjects demonstrated a mean 15.2-kg (33.4-lb) weight loss. From weeks 44 to 96, during the unsupervised period, 14 of the 22 subjects (64 percent) gained more than 5 kg (11 lb). No significant differences were observed among the women in the three diet and exercise groups at week 96. Assessment of glucose tolerance during the study period revealed that fasting glucose levels and glucose levels obtained after a 75-g glucose load did not differ among the groups throughout the study.

The mean fasting insulin level and the mean insulin level in response to oral glucose decreased significantly from baseline to the 44th week, after weight loss had been achieved. The type of exercise program (i.e., aerobic or strength training) or the lack of an exercise program did not have a bearing on insulin levels. In the 22 subjects followed for 96 weeks, fasting insulin levels and insulin levels after the glucose load rose from baseline in 19 of the subjects (86 percent) so that at week 96 their insulin levels were not significantly different from baseline levels.

This was in contrast to weight, which remained significantly lower than baseline weight. The authors conclude that their study corroborates the benefit of weight loss on hyperinsulinemia in obese persons. The addition of exercise, however, was not found to provide additional improvement, and a marked increase in insulin levels was noted with only a partial regaining of weight. Further studies are needed to investigate whether insulin sensitivity can be improved with more sustained weight loss or whether a defined basal metabolic index is required to improve insulin sensitivity.

Weight-loss news that's easy to stomach. University Diet & Nutrition Letter v14, n2 (April, 1996):1 (1 pages).

COPYRIGHT Tufts University Diet and Nutrition Letter 1996

Ever hear talk about how the stomach shrinks after a person has been dieting, resulting in less hunger than previously? Well, the stomach - a grapefruit-sized organ when empty - can't really get any smaller. But new research shows it does lose its capacity to stretch as much as it did when it was accustomed to holding more food. And that makes a dieter feel full on less.

Investigators at Columbia University's Obesity Research Center proved the point when they measured the holding capacity of 14 obese people's stomachs both before and after putting them on a weight-loss regimen. To make the measurements, the researchers threaded balloons into the subjects' stomachs through their mouths and throats and gradually filled them with water. After each two-fifths of a cup, the men and women rated their feelings of fullness, nausea, and abdominal bloating on a scale of 1 to 10, with 10 being the worst. When a participant rated discomfort at 10, the balloon filling stopped.

Before beginning the diet, the men and women, who weighed on the order of 220 pounds, could hold an average of almost four cups of water in their stomachs.Four weeks later, when they had lost anywhere from 12 to 28 pounds, their average holding capacity before they reached 10 on the discomfort scale was less than three cups - a decline in stomach capacity of 27 percent.

A second test in the same subjects relied not on their subjective responses but instead used a machine to measure the pressure exerted on the stomach wall with increasing amounts of water. In this test, stomach capacity went down by 36 percent In fact, after four weeks of dieting, the women could no longer hold any more volume in their stomachs than a group of normal-weight women observed in a separate study.

The researchers hypothesize that it is not obesity per se that increases stomach capacity but overeating. Specifically, the problem appears to be eating large individual meals rather than eating too many calories over the course of the day. Consider that normal-weight bulimics, who sometimes eat thousands of calories at a time during binges, have even greater stomach capacity than obese people of the same age.

A larger stomach capacity not only makes it easier to eat larger meals; it also apparently increases the desire for them. The researchers point out that the stomach has special "stretching sensors" responsible for sending signals to the brain to induce satiety. But they believe the sensors may not get the signals going until the stomach has been distended to a certain proportion of its capacity. Therefore, the more the stomach can hold, the larger the meal needed to inform the brain that a person is full.

Fortunately, the converse appears to be true as well. The less food the stomach becomes used to holding comfortably, the less it takes to inform the brain that the body has had enough to eat. That's good news for dieters.

Bovsun, Mara The diet dilemma. (includes related articles) (Cover Story) Medical World News v33, n5 (May, 1992):17 (6 pages).

COPYRIGHT Medical Tribune Inc. 1992

At age seven, Helena Spring started dieting. After 34 years of grapefruit, 270-calorie-a-day hospital plans, fat camps and weight-loss clinics, she stopped. Now 43, the 5 foot 3 inch nurse weighs about 300 pounds. "I'm much happier with myself since I stopped dieting," she said. "I think the word diet should become extinct."

Spring, a member of the Sacramento, Calif.-based National Association to Advance Fat Acceptance, is part of a growing rebellion against calorie counting, starvation diets and the $33-billion-a-year diet industry. For people like her, the question is no longer "which diet" but whether to diet at all.

"Diets don't work and permanent weight loss is elusive," said Sally Smith, executive director of the 3,500-member group, herself a 300-pound woman, who also started dieting when she was seven. "Fat people are here to stay."

A small group of physicians and therapists have joined the diet backlash, according to Joseph McVoy, Ph.D., director of the 120-member Association for Health Enrichment of Large Persons.

"We are at a crossroads," Dr. McVoy said. "It is time we have to change our underlying assumptions about the world.

" Dr. McVoy, who runs an eating disorders clinic at St. Albans Psychiatric Hospital in Radford, Va., said that for 30 years there has been research showing that dieting is not effective for long-term weight control. "There is no diet that can show you a success rate of five years," he said. "Why do we continue to torture these people when we know it doesn't work?"

Practicing physicians are beginning to question whether everyone can, or should, reduce. "It's a kind of madness to say that everybody should lose weight," said Dr. Alvin J. Ciccone, a Norfolk, Va., family physician who admits that he is an "overweight doctor," and does not practice what he preaches. He said he lost about 100 pounds, only to gain back half of the weight.

"The problem with America is that everybody feels that to be thin is to be healthy," he said. "I wonder if this is not a gimmick of America."

The anti-diet revolution alarms Dr. Theodore VanItallie, a leader in obesity research since 1952. "It is a disheartening spectacle to observe so many victims of our obesity-promoting environment collaborating actively in their own downfall," he said. "They shouldn't participate."

Dr. VanItallie says there is overshelming evidence that fat people have an increased risk of diabetes, coronary heart disease, hypertension, gout, gallbladder disease, and endometrial and breast cancer. Fat women, for example, run six times the risk of developing gallstones as their slim counterparts.

"The doctor has the responsibility to inform patients of these risks," he said. "To say that no one should diet is ridiculous."

The health paradox

At a National Institutes of Health (NIH) consensus development conference held in early April, a panel of obesity experts observed a "health paradox" in modern America--many people who do not need to diet are trying to do so, while others who may need to lose weight for health reasons are not succeeding.About one-third of American women and a quarter of American men are trying to lose weight at any given time, according to the NIH, and they spent about six months of the last year on the various weight-loss regimens. The panel also concluded in its consensus statement that those who take part in weight-loss programs quickly regain whatever they lose. The long-term failure rate is estimated at 95%.

"We're in an epidemic of dieting inappropriately," according to internis/endocrinologist Dr. C. Wayne Callaway, of Washington, D.C., and a member of the Dietary Guidelines Advisory Committee of the U.S. Department of Agriculture. Dr. Callaway estimates that only one in 10 women who diets does so for health reasons. "The guys with the beer bellies are not trying to lose weight," he said. "Ironically, those are the people who most need to drop pounds, because abdominal fat poses the greatest health risk."

Despite the dieting craze, Americans are getting fatter. The latest data from the National Center for Health Statistics' health and nutrition survey show that 25% of the adult population, or 34 million Americans, are 20% or more over ideal body weight.That number is within one percentage point of the figure given for the previous two studies, covering five-year spans. NIH statistics put the figure for overweight Americans closer to 34%, said Dr. Jay H. Hoofnagle, director of the division of digestive diseases and nutrition for the NIH.

Fast and abundant food and hectic but sedentary lifestyles helped to put on the weight, and spawned the diet industry. The Calorie Control Council, a diet-food trade group in Atlanta, Ga., said that about 48 million Americans are on diets, and 101 million are eating light, surgar-free or low-calorie fare, according to a 1991 survey.The number of dieters is down from the 1986 figure of 65 million. But at that time, there were only 78 million consumers of pared-down foods.

In 1989, about 1,000 new light products were introduced. Estimates for the total industry--diet books, fitness spas, commercial and hospital-based reducing plans, foods, pills and supplements--were in the range of $33 billion in 1991, according to Marketdata Enterprises, Inc., a consulting firm in Valley Stream, N.Y.

If the diets are doing little to slim down the American population overall, they have been wreaking havoc with those people caught on the diet merry-go-round, commonly known as yoyo dieting. The psychological impact of losing and regaining over and over can be devastating.

"I felt like a total failure. I had no sense of self-worth," said Aleta Walker, 35, who carries about 300 pounds on her 5 foot 6 inch frame. She started her life-long diet, which she said cost "tens of thousands of dollars," at age 12, when her doctor prescribed amphetamines and a 500-calorie meal plan. She quit just five years ago, after her second attempt at a liquid diet gave her gout. "All the diets have contributed to my being the size I am today," she said. "I was hungry all the time, constantly hungry and deprived."

That deprivation leads to depression and binge eating, said San Diego therapist Susan Ward, who runs a group she calls Beyond Feast or Famine. Her patients are encouraged to throw away the diet books and eat when they are hungry. But her major goal is getting her patients to abandon the self-loathing that accompanies repeated failed diets. Do they lose weight during her 12-week program? Ward admitted that some do, but most don't. When Ward takes people off diets, they "run rampant," she said. "Maintaining weight, not gaining, is a big goal." She focuses on getting her patients to start an exercise program, and make healthier food choices.

Dr. Callaway said that the idea that people can control their body fat is simplistic, and "based on the notion that all fat people are gluttons." This idea totally ignores heredity, he added. "Physicians think it is a matter of control, when 50% of the variation in weight is genetic," he said, citing studies on adopted twins that showed that no matter where a child was raised, weight patterns reflected those of the biological parents. "We start out with a pre-set tendency to be a specific height and weight," he explained.

Research is also indicating that genetically heavy people are sabotaged by their own bodies each time they try to lose weight.

"Our many years of research into the biological effects of weight reduction have shown that weight reduction is accompanied by metabolic changes that return the patient to the antecedent weight," said Dr. Rudolph L. Leibel, an associate professor at Rockefeller University in New York City, who has been studying obesity for 12 years. Long-terms efficacy is very difficult to achieve because calorie restriction provokes compensatory alterations in the body's use of energy.

Human bodies were designed to survive famines, and that mechanism undermines low-calorie diets. "If you cut back on your food, your body will adapt to starvation by burning less and less," Dr. Callaway said. In a normal person, food decreases appetite, he said, but it has the exact opposite effect in a person who has starved.

More harm than good?

A big surprise at the NIH meeting was a collection of epidemiologic studies contradicting the conventional wisdom that extra fat shortens lives. David F. Williamson, Ph.D., an epidemiologist in the division of nutrition at the Centers for Disease Control, Atlanta, said that what "made people sit up and take notice" were 15 studies observing trends among several hundreds of thousands of people, all pointing to the possibility that dieting--not being fat--may increase a person's relative mortality risk about 1.5 to 2.5 times. "I was surprised by the consistency of the data," Dr. Williamson said. Another issue that "struck a number of us" was the strong relationship between weight loss and cardiovascular mortality, he said. "That is a twist that has puzzled folks." Dr. Williamson hypothesized that the cardiovascular complications may be a result of the loss of lean muscle tissue that is commonly seen with low-calorie diets.

Since epidemiology is an inexact science at best, Dr. Williamson said that the studies reported at the NIH need to be taken seriously, but require further study in a more controlled setting before they can be used to determine medical recommendations. "The anti-diet people are looking at this as another brick in the wall of their argument," he said.

Dr. F. Xavier Pi-Sunyer, co-director of the Center for Research in Clinical Nutrition at St. Luke's/Roosevelt Hospital Center in New York City, views the research on the dangers of weight cycling as "inconclusive." But he said that trying to set a predetermined weight goal for a fat person is not advisable.

Dr. Pi-Sunyer said that obesity-related health risks do not start until a patient is 20% or more above ideal body weight, or if there is an existing condition, such as hypertension. "There is reasonable data to suggest these people will benefit from losing," he said. "But they don't have to lose all their weight, reach a goal on the actuarial tables, to get a health benefit.

"If a person weighs 290 pounds, it makes no sense to choose a goal weight based on the average height-weight tables," Dr. Pi-Sunyer continued. "The initial weight loss might be 15 pounds, achieved slowly at a maximum rate of about two pounds per week. We do it in increments; we don't set the patient up for failure by moving too quickly."

Reducing programs should be based on an invididual's metabolism, not a pre-printed menu card, and a great emphasis should be placed on improving diet composition, reducing fats, for example, Dr. Callaway said. "The idea that everyone will lose weight on a 1,200-calorie diet is silly," he said.

Extreme measures, such as gastric reduction and 400-calorie liquid diets, should only be considered when there is a clear sign that a patient has an obesity-related disease, Dr. Pi-Sunyer said. "We consider gastric reduction only for people who have serious effects of obesity, such as heart disease," he said.

Ironically, by removing the patient's contact with a realistic eating environment, these techniques succeed in helping patients dro pounds, but fail in helping them keep the weigh off. "They don't have to think about it," said Dr. Pi-Sunyer, who added the same is true of ultra-low-calorie liquid diets. "When people are on a liquid diet, they don't deal with food, so they don't learn much," he said. "What one wants to do is get them to change lifestyles."

Both anti-diet and traditional weight-loss advocates agree that some form of exercise is crucial in maintaining weight loss or establishing a healthier lifestyle, no matter what the scales say.

Whether patients weight 150 pounds or 600 pounds, they require "healthy physical activity" like walking, Dr. McVoy said. But shoving a formerly sedentary 500-pound person into "an aerobics class with mirrors, and a lot of lycra and spandex" is sure to fail. Slowly, painlessly introduce the activity, Dr. McVoy said, and the patient will continue and make it part of a daily routine. With one of his larger patients, he said he recommends five minutes on a treadmill. "Now that patient walks about a mile a day, and has slowly lost 100 pounds," Dr. McVoy said. "Water aerobics is another good choice because the water's buoyancy reduces joint stress."

Dr. VanItallie said that the activity level recommended for cardiovascular fitness--20 minutes a day, three times a week--is not adequate if you want to burn calories. "It does not have to be rigorous," he said, nothing that two hours of walking a day consumes nearly 500 calories.

Unless a person is willing to make exercise and eating less a lifetime commitment, Dr. VanItallie believes that it is a waste of time to start a weight-loss program. "The physician has to assess whether the patient has an understanding of the problem and the intellectual ability to change lifestyle and manner of eating," he said.

As in other chronic conditions, earlier intervention may keep the problem from getting out of hand. "Don't wait until a patient is 300 pounds," Dr. Pi-Sunyer advised. If weight starts to drift about 20% above normal, he said it is time to alter lifestyle with small increases in activity and decreases in caloric intake. Early interventions can be valuable for preventing obesity in women, who in general continue to gain weight throughout adulthood.

On the flip side, he said that his clinic turns away people who say that they want to lose 15 pounds just to fit a cultural image. "There, I tend to agree with the anti-diet people," he said. "The ideal image out there of women who are so thin is biologically incorrect." He estimated that fashion models may have body fat around 6%, where an average woman will carry around 20% to 25% of her weight in fat.

Dr. VanItallie summed up the problem by stating, "In prehistoric times, primitive man hunted for food; modern man is hunted by food. While we can't change society, patients have to learn to defend themselves against this."