Defining Obesity

As you know, obesity is a common problem in the States, affecting on the order of 35-40 million adults. One may assess obesity by determining a person's excess weight in comparison to an "ideal body weight (IBW)" or by using body mass index (BMI = body weight in kg/height in m2). In general, most medical literature uses BMI to determine obesity, with values greater than 27 considered obese. IBW is determined by referring to the Metropolitan Life Tables. The most recent update is from 1983. My impression is that the upper end of the large frame group serves as a useful reference for a practical IBW. The following will give you an idea of how to grade obesity, and relate it to increased mortality risk:

The risk of dying is greatly increased in those with severe and morbid obesity. In fact a subgroup of the morbidly obese (the "super morbids", with body mass ≥250 % of IBW), are at extremely high risk, with most dying prior to the age of 60 yo. The increased mortality in obesity is secondary to the associated diseases it contributes to (e.g. DM and Htn), as multivariate analysis shows little increased risk from obesity, per se. In addition to DM and Htn, with the consequent effects on blood vessels, those with moderate or greater obesity are also at increased risk of endometrial Ca and GB pathology (cholelithiasis and Ca). Even less serious disorders like osteoarthritis are twice as common in the obese versus non-obese, as are menstrual disorders such as amenorrhea (the elevated estrone levels derived from peripheral conversion by fat cells likely contributes to this as well as the increased risk of endometrial Ca).

In general, it is clear intervening in moderate and severe obesity can be helpful. This has been demonstrated by the fact that about 1/3 of these patients will no longer require pharmacologic treatment of Htn or DM after significant weight loss (generally on the order of 30-50 pounds). In addition, another 1/3 will require less medication. Similar benefits can be seen in the morbidly obese population, but the amount of weight they need to lose to derive these benefits is usually greater.

The more difficult question arises in the mildly obese. Is there sufficient reason to recommend weight loss in this population? As usual, the answer depends on their exact risk profile, in addition, to their active disease burden. Thus, your approach to managing a 30 yo person who is 130% of IBW, will depend on whether they are well otherwise, or not.

The etiology of obesity, as you would expect is multi-factorial. The range of metabolic rates (adjusted for body weight) tends to follow a Gaussian distribution (i.e. bell shaped curve). Thus, 2/3 of people will be within 50-75 kcal of that calculated by the Harris-Benedict equation (i.e. the approx. mean metabolic rate for a given age, sex, height and weight). Going out 2 SD to include 95% of people will lead to 125-150 kcal deviations from the mean metabolic rate. On top of this presumed "genetic" component are other factors such as a sedentary life style, use of food for reasons other than nutritive value and pharmacologic factors (e.g. the effects of nicotine in smokers). The effect of smoking on RMR is about 50 kcal per day. Thus, every 80 days after quitting smoking, assuming food intake remains constant, a person would gain one pound of fat. As a result, weight gains in excessive of 5 pounds per year after quitting smoking can not be attributed to the metabolic effects (improved gustatory sense after quitting seems to be a more notable contributor to post-smoking cessation weight gain).

Methods of Weight Loss

1. Balanced Deficit Diet (BDD): this method, as implied by the name, involves on overall decrease in calories from the major sources (fat, protein, carbohydrate and alcohol, potentially). In general, fat is the major focus, though portion size changes may also be important.

   A reasonable approach in the moderately obese is to identify very high fat sources using 24 hour recall and through specific questions (re: cheese consumption, fried foods, butter or margarine, mayo and the deadly pizza). You may be able to identify enough of these to decrease calories by several hundred a day. Each 50 kcal decrease in consumption will lead to a 5 pound fat loss in a year.

   At follow-up, food records may helpful to further identify problematic foods, and to monitor adherence to a meal plan. The number of calories prescribed each day can be decreased to as low as 1200 per day without problems. How closely one is monitored medically is dependent on the rate of weight loss. A morbidly obese person can lose 4-6 pounds a week on a 1500 kcal/day diet. This rate of weight loss would require monitoring as noted below for VLCD.

   When setting up a meal plan, one tries to determine the food preferences of the patient, and help them define an attainable organization of their daily food intake. One will usually define it as follows:

   Food	Serving Size	kcal/serving	protein	fat
   Fruit	one small to medium piece	60	none	none
   Starch	(e.g. Bread one slice)	80	3 g	0-1g
   Vegetable	1/2 cup cooked	25	none	0
   Protein, Lean (cooked)	1 oz. poultry or fish	55	7g	2-3g
   Protein, Medium fat	1 oz pork, ham, lean beef or 1 egg	75	7g	5g
   Protein, High fat	1 oz steak or corned beef	95	7g	7g
   Milk, low fat	1 cup skim or fat-free yogurt	80	9g	0g

   Thus, a meal plan (BDD) may look like:

   Breakfast:	2 breads (toast or a bowl of cereal) and 1 milk (1 cup of skim or 1%)	OR	2 fruits (a grapefruit) or 1 fruit and 1 bread (e.g. toast with spreadable fruit)
   Lunch:	2 breads, 3 lean meat and 1 veg. (e.g. a sandwich w/ lettuce, tomato and mustard)	OR	2 veg. and 1 bread or milk (fat-free yogurt) (e.g. a salad with low fat dressing)
   Dinner:	4-6 oz of meat, 2-3 veg. and 1 bread	OR	3-5 bread with 2-3 veg. (e.g. pasta w/ fat-free tom. sauce and small salad)
   AM/PM snack:	1 fruit serving	OR	1 bread serving (e.g. 5 low fat crackers)

   This would amount to 1100-1500 kcal/day, depending on how it is embellished, with 40 g of protein, and a good balance of vitamins and micronutrients. Depending on weight loss and feed back you receive from food records or questioning about food choices, modifications can be made.

2. VLCD (very low calorie diet): this type of diet is also referred to as a protein- sparing modified fast (PSMF). It evolved from studies on complete fasting in the 1950s. It was noted during fasting that significant lean tissue losses led to complications. Thus, protein supplements were added to the fasting protocol. In the late '60s, liquid protein diets gained popularity. What we learned, was that the quality in addition to the quantity of protein was important. Initial products utilized hydrolyzed collagen as the protein source, with fatal consequences (nobody needs that much proline). In addition to improved liquid protein supplements to accomplish rapid, effective and safe weight loss, it was noted that large amounts of meat with limited carbohydrates could serve the same purpose.

   The liquid shakes which are used in VLCDs (e.g. HMR at Evans Nutrition, OptiFast, Medifast, etc.), are supplemented with vitamins, though an additional K+ supplement is often used. When using meat as the protein source (PSMF), ideally 1.5 g/kg of body weight is used, though often a total of 70-100 g per day is sufficient. In the case of a PSMF, a multi-vitamin, 1 g of elemental Ca++, and 20 meq of K+ is required.

   Physiologically, a VLCD/PSMF will lead to ketosis, which allows fat to serve as a major energy source. In addition, when high quality protein is used (i.e. biologic value near 1), there is good preservation of lean tissue. The consequences of these physiologic changes can help one to focus on the potential complications, and thus, what aspects of one's medical care requires monitoring:

   • Diuresis from ketosis: due to the negative charges of ketone bodies, significant Na+ losses occur. Thus, patients on diuretics often have them stopped when they begin a VLCD. The diuresis is greatest in the first few weeks of the diet, and most patients will note increased urination. Often the diuresis is so brisk that patients become dehydrated. Dehydration requires the oral equivalent of normal saline, bouillon. Each bouillon cube contains approx. one gram of sodium. Generally, 3-4 cups of bouillon are required for 2-3 days to relieve symptomatic dehydration.

     There is a general recommendation that people on VLCDs drink at least 2 quarts of non-caloric beverages each day to avoid dehydration. It is often stated, for reasons unclear to me, that people should drink at least eight 8 oz. glasses of water a day when dieting (a Weight Watchers favorite). Water is actually generated by the oxidation of fats, and thus, this consumption couldn't logically enhance that process (if anything, by mass action, it would retard it).

   • Nitrogen Balance: it takes 7-10 days in women and 14-20 days in men to get into nitrogen balance with onset of a VLCD. Thus, care needs to be taken to ensure that compliance with the dietary prescription is not lax. Patients who need to lose sufficient weight to qualify for a VLCD (i.e. generally, severely or morbidly obese), are so obsessed with losing weight that they don't mind missing a meal or protein supplement. This can actually be quite dangerous, as it may exaggerate lean tissue losses.

     The vital organ which gets the most attention on VLCDs is the heart. It turns out, based on the data generated during the spat of deaths during the late '60s with the collagen based liquid protein diets, that the QTc interval is the best predictor of someone having excessive lean tissue losses from the heart. Thus, an ECG at baseline and with every 30-40 pounds of weight loss is accepted as adequate monitoring.

   • Constipation: the residue of a VLCD/PSMF can be quite low. Thus, fiber supplements such as metamucil are often helpful in maintaining regularity (as is attention to fluid status).

   • Gall Stones: there is a high incidence of new gallstone formation in people on VLCDs. 25% of those with normal GB by U/S at the start of a VLCD, will develop gallstones in 8 weeks time. However, the vast majority of these stones will redisolve on continued follow-up, and symptomatic gallstones become evident in less than 1% of pts. on a VLCD (which includes people with stones pre-VLCD, as the obese are much more likely to have stones than the non-obese). Concerned patients can essentially eliminate this risk by taking 600 mg bid of ursodiol while on the VLCD.

   Weight loss on a VLCD is on the order of 2-4 pounds of fat per week for women, and 4-6 pounds per week for men. The most likely reason for lack of sufficient weight loss in any week or two week period is fluid retention (which is quite common in women peri-menstrually). However, this cannot serve as justification for inadequate weight loss over several months. Calories range from 500-800 per day on VLCDs. The advantage of a 500 kcal/day (i.e. more rapid weight loss) is short lived, and when studied over 12-20 week time periods, people lose as much weight on 800 kcal/day diets (this initial difference may in part be due to decreased metabolism which occurs with severe caloric restriction).

   These types of diets (VLCDs) are usually done in conjunction with a program which includes nutritional education and behavioral modification. There is no good 5 year data to date with these types of programs. The five year data on medical treatment of obesity in general, which would include BDD and VLCD, is that only 2% of those treated maintain their weight loss. It is not clear what level of success these multi-disciplinary treatment programs will have, or if the maintenance programs they have devised will have any effect. My guess based on the 500+ such patients I have personally treated is that at best it would be on the order of 10%.

3. Surgery: if you want good data 5 years later, then surgery is the answer. In experienced hands, gastric restriction with bypass can yield maintenance of weight loss in more than 50% of those treated.

   The side effects can be well managed, especially if medical therapy with a VLCD is done to get 50-100 pounds off pre-surgery, to minimize the fluid shifts and lean tissue losses that will occur with any form of rapid weight loss. This type of surgery is reserved for the morbidly obese, though it could very well be beneficial in the severely obese, also.

   Other forms of surgery are no longer performed, due to unacceptably high complication rates. Besides post-prandial pain, and N/V, the side effects of gastric stapling are similar to those at the beginning of a VLCD.

4. Pharmacologic therapy: in the mid-1990s,drug therapy has came back into vogue for obesity. In the past, amphetamines had been used with significant weight loss, but also unacceptable side effects. In 1991, Michael Weintraub published a detailed series of reports on low dose therapy of two medications to treat obesity. His premise was that continued treatment, over long time periods, with low doses of effective medications, could yield adequate results with minimal side effects, not unlike the treatment of Htn.

   He studied the use of phentermine, 15 mg a day (an amphetamine), along with 60 mg of a slow-release form of fenfluramine. He found that people lost weight, and could sustain that weight loss, as long as they continued on the medication (his study lasted 4 years). Side effects, were largely GI for fenfluramine, and nervousness/insomnia for the phentermine. The only problem with the study was a high drop out rate, which may have made the results appear more favorable.

   Subsequent studies showed that this combination, often referred to as "phen-fen" or dex-fenfluramine as monotherapy, could produce sustained, weight loss, as long as patients remained on therapy. Initial concerns of toxicity included an increased incidence of pulmonary hypertension (1 in 100,000). However, since this disorder may be increased in the obese due to its relationship to obstructive sleep apnea, its importance was unclear.

   By 1997, it became clear that valvular heart disease could occur in people who took fenfluramine, even for short periods of time. The incidence was initially overstated at 30%, but subsequent, prospective studies found the actual incidence to be on the order of 2-5%. Yet, in previously healthy people, this was clearly an unacceptable rate of serious side effects. Thus, fenfluramine was withdrawn from the market, but its more innocuous partner, phentermine, has remained.

   The exact mechanism of weight loss with amphetamines is not clear, but they have been used for many years to help with weight loss (the generic term for such drugs is "anorexiants"). Ephedrine has been studied in short term studies, with effects similar to phentermine. (In fact, many of the "herbal" weight loss therapies use a combination of ephedra and caffeine, which have been established as effective agents for sustaining SHORT TERM weight loss). Finally, second generation stimulants have been released, such as Meridia, and agents to affect absorption of fat, Xenical. These agents, haven't passed the test of time, and thus, are still, used with caution at this time.

   Other drugs which act via serotonin are the SSRIs. Drugs such as fluoxetine (Prozac) and sertraline (Zoloft), have been studied as anorexiants. They have shown efficacy in 4-8 week trials, but the effects tend to wear off. In contrast, the anorexiant effect of fenfluramine appears to be durable. The long term side effects of such treatment regimens are just being worked out.

Weight "Cycling"

This topic gained much lay press a couple years ago, when a group of researchers, using several major, prospectively collected data bases (e.g. Framingham), found a relationship between weight "change" and mortality. The measure of weight change they studied was the "coefficient of variation", which served as a statistical measure of weight "changes" over time (the authors assumed this represented weight "cycling").

The problem is knowing what the coefficient of variation actually measures. It may not be related to what we refer to clinically as "weight cycling" (i.e. the weight is lost and regained, over and over again). In fact, Rena Wing of the U. of Pitt, showed quite clearly that a slow continuous weight gain, or loss over time would yield a coefficient of variation which implied "cycling". In addition, when animals have their weights cycled, no impact on mortality is noted, nor is it clear, what the mechanism of increased mortality would be in humans. Finally, the effects noted were quite variable. Men would have a slightly increased mortality (e.g. 30% increase versus control) in one study, and women in another.

Thus, in summary, weight cycling is a real clinical problem. However, it has never been studied in a clinical situation. As a result, no clear answer exists about potential risks, if any, which may exist.

Getting back to the basics

• Define extent of obesity (in BMI or % IBW)
• Establish active medical problems related to obesity, and associated RF.
• Set-up a management plan. Try to be clear about your goals, and what your likelihood of attaining them are. If risk and disease burden are low, and degree of obesity is moderate, there is plenty of time to focus on gradual life-style modifications. If the disease burden warrants, seeking additional help from consultants may be helpful.
• Try to keep expectations in line with reality. Patients cannot expect to lose large amounts of weight weekly, or even monthly on a BDD. Use your knowledge of how to calculate metabolic rates and their estimated caloric intake to help define expected fat loss per week (e.g. If the patient weighs 250 lb., their estimated MR is about 2500 kcal per day. If they adhere to a 1200 kcal/d diet, they will burn about 1 pound of fat every three days. Thus, two pounds of fat would be burned each week.
• Keep in mind the role of exercise. Exercise can burn an additional 100-150 kcal/mile walked or jogged. Thus, the patient above would have to walk about 10 miles a day to "lose" as many calories as they do from their caloric deficit. This doesn't mean exercise should be ignored, but it also is not a panacea. In the apt pt., exercise may be a great modality, especially if the amount of weight to lose is not great, and if they display the patience to comply. However, exercise has clearly demonstrated its importance in weight maintenance, after the initial weight loss. It also may be helpful in preserving lean tissue during weight loss (though this data is still quite equivocal).