October 1, 1999

Obesity: State-of-the-Art Update

Joel Mason, M.D., and Edward Saltzman, M.D.
Dr. Edward Saltzman teaches at the Tufts University School of Medicine and is a member of the Division of Clinical Nutrition. Dr. Saltzman is Medical Director of the Obesity Consult Center at New England Medical Center and his research interests focus on the control of energy metabolism.

How would you define obesity?

Obesity is a condition that is easy to recognize but difficult for many people, even doctors, to define precisely. Technically speaking, obesity is an excess of body fat. However, in any person, it's pretty difficult to measure their body fat. The old-fashioned way, involving calipers, a two-legged adjustable instrument that measures skin thickness, and the modern high-tech, costly alternative, dual photon absorptiometry (DEXA), which is also used in the diagnosis of osteoporosis, are not routinely done. Instead, we measure body weight and trust that it gives us a good approximation of an individual's body fat. The most common reference point for "ideal weight" has been the Metropolitan Life Insurance Company's Weight Tables.

A better measure of weight, however, is the body mass index (weight in kilograms divided by the height in meters squared). The BMI is a relatively height-independent measure of body weight. By convention, a body mass index of 30 or above is designated as obesity. For some of the large surveys done in the US and other countries, overweight is defined as a body mass index greater than 27.8 or 27.3 for men and women, respectively, because many of the medical problems that accompany obesity start to increase between the 27 to 30 range.


I have seen several news reports suggesting that the prevalence of obesity in North American society is increasing, especially among children. Is this really true, or is this increase simply related to changes in how we define obesity?

It's increasing. No doubt about it. In North America, Europe and even in some parts of the developing world. Obesity has become so frequent in the US that it is now often called an "obesity epidemic." The prevalence of obesity in the US is approximately 30%. Among some minority population age groups, almost 50% of the individuals are obese.

Associated Medical Problems

There are many medical and psycho-social complications of obesity. The common ones include an increased prevalence of Type II diabetes, hypertension and osteoarthritis. What are some other, less well-known problems?

Many moderate and severely overweight individuals have some degree of obstructive sleep apnea, a condition where they temporarily stop breathing during sleep. We always ask our patients if they fall asleep in the daytime or have disturbed sleep in the evening, and we also ask about more subtle changes, such as diminished cognitive capacity and mood disturbances. I think you will find a mild, smoldering type of depression is quite common in obese individuals and I strongly believe that disturbed sleep contributes to this in many persons.

One very important point for everyone to remember is that if an obese person receives effective treatment for these emotional issues, they will usually have an easier time losing weight.

Ed, given how many obese people suffer from sleep apnea, in one study more than 40%, do you think all obese individuals should be screened for sleep apnea?

We need to treat the patient and not just look for associated disorders. One exception to this may be the obese patient with hypertension who also has symptoms of sleep apnea, since there appears to be a link between hypertension and sleep apnea. Even those patients who appear to be functioning well during the day but are hypertensive should be considered candidates for a formal sleep study.

Pharmacologic Treatments

Given the great concern over potential side effects, what's your opinion about the new anti-obesity drugs?

There is a place for drug treatment in obesity but it has to be as part of the broader program — dietary modification, increase in physical activity and lifestyle changes. Medications make it easier to achieve the weight loss goals set forth in those basic treatments.

As of May 1999, the currently available medications include the adrenalin-type drugs, such as phenylephrine, appetite suppressant drugs, such as phentermine, which work on the central nervous system to decrease appetite and food intake and sibutramine (Meridian®), which is a selective serotonin re-uptake inhibitor, acting on the central nervous system to decrease food intake and make you feel "full." Compared to a sugar placebo, sibutramine promotes a 5-10% decrease in body weight when used over a 6-12 month period. This 5-10% decrease in body weight may seem small, compared to the total degree of overweight, but a 5-10% decrease confers dramatic improves an individual's health.

Another drug, tetrahydrolipstatin [Xenical® (orlistat)], recently approved by the FDA (April 1999), does not act on the nervous system to control appetite but instead blocks the work of a pancreatic enzyme involved in the body's absorption of fat. As a result, approximately 30% of ingested fat does not enter the bloodstream. Indeed, for people taking Xenical® (orlistat) eating high fat foods may be unpleasant because the unabsorbed fat appears in the stool, producing oil bowel movements.

There is a place for drug treatment in obesity, but it has to be as part of the broader program of dietary modification, increase in physical activity and lifestyle changes.

Drug Side Effects

Let's return, for a moment, to the drugs that act on the central nervous system. The Phen-Fen combination (phentermine and fenfluramine) was pulled off the market because there was some evidence that these drugs damaged heart valves. What do you think about one drug, either phentermine or subutramine, by itself? What are their side effects?

Recent reports appear to suggest that the incidence of valvular lesions with the fenfluramines may be less than the 30% prediction based on initial reports. Nonetheless, this research is yet to be completed. As far as we know, phentermine, as a single agent, is not associated with valvular heart disease. However, the use of phentermine with Prozac®, the so-called "phen-pro" combination, is not recommended because this combination may mimic the effects of the fen-phen combination. While there is no evidence to state that this is so, there is no evidence yet to refute this proposition.

We have found that phentermine (but not the newer agent, sibutramine) appears to be associated with a small risk (one in 20,000 individuals who take these drugs) of primary pulmonary hypertension. It would be prudent to consider all these agents as possibly inducing pulmonary hypertension until proven otherwise.

The common side effects of sibutramine include dry mouth, constipation, insomnia and headache. Of most concern would be increases in blood pressure or heart rate. For most patients, the average increase in blood pressure is very small but others may experience a rise greater than 15 millimeters. For this reason, patients with hypertension should have their blood pressure checked frequently when they use these medications.

Can you discuss some of the potential side effects of Xenical® (orlistat)?

Most of the side effects are almost entirely attributable to its mechanism of action — blocking the digestion and absorption of fat in the intestine. These side effects are common when patients first start taking Xenical® (orlistat), but it appears that patients quickly learn the degree to which they can tolerate a small amount of fat in the diet and adhere to that thereafter. The other complications of Xenical® (orlistat) theoretically result from decreases in absorption of some of the fat soluble micronutrients and that's why the manufacturer recommends the routine use of a multi-vitamin supplement. In the pre-marketing trials of Xenical® (orlistat), small (and probably clinically insignificant) decreases in the levels of some of the fat soluble vitamins were seen and were stable over a period of over one year. However, the long term effects of Xenical® (orlistat) on some of the more obscure or unmeasurable micronutrients remain unknown.

Other Treatment Modalities

Aside from drugs, what other regimens do you recommend?

As I said before, the cornerstones of treatment for overweight are long term dietary changes and increased physical activity. You need a comprehensive plan that pays attention to all the factors associated with an individual's given lifestyle that promote overeating.

Bariatric Surgery
In addition, we also, at times, recommend people for bariatric surgery. In the most commonly done surgery, the roux-en-y gastric bypass, the stomach is stapled in order to reduce its size and its ability to hold food. This is a treatment option for those individuals who are greater than 200% of ideal weight or whose body mass index is greater than 40 kg/m2. For individuals in this weight class, this is the single treatment most likely to result in a decrease to a healthy weight and maintenance of this healthy weight. Obviously, such a dramatic change in one's capacity to eat, via surgical intervention, is not for everyone.

Genetics and Obesity

Does genetics play a role in obesity?

Family studies and identical twin studies demonstrate that the heritability of body mass index is probably in the neighborhood of 30-40%. The knowledge that body composition has a significant genetic determinant doesn't help us, however, with an approach to individual patients. Clearly, there will be families in which obesity is very common. However, what enables one member of that family to lose weight will not necessarily work for the others.

There are a number of factors that are probably under genetic control that are thought to influence body weight. These include the protein, leptin, as well as other hormones such as neuropeptide Y.

There are a number of factors that are probably under genetic control that are thought to influence body weight. These include the protein, leptin, as well as other hormones such as neuropeptide Y. Leptin is a protein produced in fat cells that communicates with the brain and which decreases energy intake in animal models. An absence of this protein in animals results in severe obesity. To date, in humans, there have been extremely few individuals found to be deficient in this protein. Trials are now underway to look at pharmacologic doses of leptin in overweight individuals to see if this is an effective way to reduce body weight. For now, the bottom line about leptin and its effect on humans, is that it's still unknown.


Are there effective ways to prevent obesity?

Prevention is critically important because treatment of obesity is so difficult. Individuals who start to gain weight (even as little as 5-10 pounds) should be counseled to try and control their weight. It is much easier to keep those individuals from gaining further weight than it will be to reduce their weight once they are 30-40 lbs. overweight.

This same strategy should also apply to children. We now have data showing that childhood obesity is associated with subsequent adult obesity, as well as subsequent health problems in adulthood. For this reason, it is important to teach children, both by example and by nutrition education, the elements of a healthy lifestyle, including appropriate diet and appropriate levels of physical activity.

I would like to thank you very much for all your insights and comments regarding this very difficult and frustrating condition that all of us will be dealing with on an increasing basis in the decades to come.

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