| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Special Articles |
Louisiana State University Pennington Biomedical Research Center Baton Rouge, Louisiana 70808
 |
Introduction |
|---|
 Top Introduction References |
|---|
The basis for the worldwide epidemic of obesity is unknown, but its existence is beyond doubt. Between 1976–80 and 1988–94, the percent of obese Americans [defined as a body mass index (BMI) >30 kg/m2] rose from 16.5% in women and 12.3% in men to 24.9% in women and 20% in men—an increase in prevalence of 50% or more 4 . Similar increases have been observed in many other countries 1 . Some of the factors involved are: less physical activity, more time in sedentary activities, high levels of dietary fat, and increased relative energy intake.
As this epidemic has been unfolding, great strides have been made in understanding the genetic basis for obesity. Twin studies 5 and studies of adopted children 6 have both indicated a strong genetic basis for obesity and fat distribution. Putting several types of data together would suggest that approximately 30% of the variance in total fat and fat distribution can be explained by genetic factors 7 . A number of candidate genes and chromosomal locations for genes involved in obesity in humans and animals have been identified (8, 9). The role of gene/environment interaction has been established for fat gain by over-feeding and exercise studies in identical twins 10 . These exciting findings and the advancing understanding of the physiology of energy balance 11 have added to the excitement stimulated by the discovery of leptin 3 . A new age of biological obesity is before us.
The current epidemic of obesity is the result of a mismatch between our ancient genes and the realities of modern life. The abundance of food, the lack of required physical activity, the ease and pleasure of being sedentary, and the palatability and variety of the food supply make overconsumption and inactivity easy. The current epidemic is clearly environmental in origin, and if it is to be halted, preventive strategies must be implemented. The growing prevalence of obesity is a time bomb that will explode with an epidemic of diabetes, hypertension, and cardiovascular disease if it is not slowed or reversed 12 .
At birth the correlation between weights of identical and nonidentical twins are the same (r = 0.6) 13 Over the early years of life, the weights of identical twins converge, but those of dizygotic twins do not. Thus, at birth obesity can rarely be predicted. By age 12–17 yr, the prevalence of overweight is 10% in girls and 6% in boys 14 . Over the next three decades, up to 75% of the population becomes overweight. Thus, at birth 25% can be categorized as "never overweight" and another 75% as preoverweight individuals who are at risk of becoming overweight during their lifetime. One-third of these preoverweight individuals become overweight before age 20, two-thirds after that 15 . From this analysis it is clear that primary preventive strategies should be focused on younger individuals, from preschool to mid-life. When primary prevention fails, then treatment and secondary prevention aimed at maintaining a lower weight become the main focus.
Can we prevent preoverweight individuals from becoming overweight? The cross-cultural studies, data on migratory populations, and longitudinal data 16 and animal data 17 argue that a high fat diet is associated with weight gain in most settings (18). Thus slowing the increase in dietary fat intake in developing countries would be a beneficial strategy. Maintaining lower fat diet and lower energy density of the food supply of developed countries might also reduce the rising prevalence of obesity, because over-consumption is more likely with high fat foods 20 .
Reversing obesity by lowering fat is a less promising 16, 19 strategy than preventing it by keeping fat low. However, a low fat diet may slow the population shift in obesity by slowing the rate at which the "genetically" susceptible become more obese. Similarly, a low fat diet may be useful in slowing weight regain of postobese individuals (20). Intervention studies at the community and school level have been effective in reducing some risk factors, but in only one study 21 was it effective in reducing BMI.
Targeted strategies may help prevent weight gain or slow the acquisition of a sedentary lifestyle. In four studies, Epstein et al. 22 have shown that weights of overweight children could be kept at a lower level over a 10-yr period after effective interventions involving parent and child. The high likelihood that an overweight child with an overweight parent will become an overweight adult makes this group especially worth targeting 23 .
The BMI originally used by Quetelet 24 is now accepted as the initial step in evaluating risk associated with obesity (1, 25 . In honor of Quetelet and his work, the BMI index might be appropriately named the Quetelet Index or QI.
QI or BMI alone, however, is not a sufficient criterion by which to evaluate the detrimental effect of obesity. Gradations in central fatness, like differences in BMI, should be used to evaluate the risk of being overweight. In addition to higher mortality rates, the risks of diabetes, heart attacks, and some forms of cancer are increased by central fatness. Weight gain after age 18–20 also predicts increased risk. A gain of more than 10 kg, or 1 kg/yr, is the dividing line for high risk. Finally, a sedentary lifestyle by itself increases mortality rates from all causes 26 .
A risk-assessment of an overwieght patient is an essential prerequisite for any treatment program, as treatment for obesity carries its own risk. The lessons from the valvulopathy reported in patients treated with fen/phen 27 points up the risk of treating obesity. An appropriate evaluation of risk is important for deciding to use medication in treating obesity.
Aronne argues that "pharmacotherapy is not appropriate for cosmetic use." He then goes on to argue the similarities between hypertension and obesity. I agree with this analogy and have used it myself 28 . However, there is one fundamental difference between obesity and hypertension. The diagnosis of hypertension requires an intermediary instrument—a sphygmomanometer. You cannot tell hypertension by looking at the patient, but you can identify the overweight individual on sight. Obesity is a stigmatized disease 12 . The desire to be thinner fuels a multibillion dollar weight-loss industry. One of the clearest lessons from the popularity of the so-called fen/phen regimen for treating obesity was the demand for it by large numbers of people. It is now clear to me that any drug approved to treat obesity will be used for cosmetic purposes 29, 30 . Such use is likely to be short-term, as opposed to the longer term use that may be needed when obesity is associated with risk factors. What the cosmetic use of antiobesity drugs suggests is that they should be held to a very high level of safety compared with drugs for hypertension or atherosclerosis. However, the use of antiobesity drugs for cosmetic purposes should not lead us to "throw out the baby with the bathwater" by forbidding the marketing of safe and effective drugs 29 .
In addition to the analogy with hypertension, obesity can be analyzed from an epidemiological perspective. Food is the agent, men and women the host, and obesity the disease. We are exposed to a surfeit of the noxious agent, food. We swim in an ocean of food. Unlike many agents, prior exposure to excess food does not produce tolerance or immunity. Indeed one of the intriguing problems of leptin (as reported by Pi-Sunyer and Laferrère, and in ref. 3) is its strong association with body fat. If leptin is a signal that triggers suppression of food intake, why do so many people become obese with high leptin levels? Obese animals are susceptible to leptin injected into the brain, suggesting that leptin is not reaching the sites that might inhibit food intake. The ineffectiveness of endogenous leptin in responding to the surplus of energy produces a tolerant state.
Tolerance to food is enhanced by its palatability and its ready access. Host resistance is also limited. Some individuals do show a resistance to food, but most continue their exposure by passive overconsumption. The positive feedback effects of food are not adequately inhibited by internal mechanisms in most people. Thus, chronic but slow overconsumption will lead to an elevated QI (BMI). Chronic exposure to the elevated QI (BMI) is what "risks fate" for developing diabetes, hypertension, gallstones or atherosclerosis, and some forms of cancer 30 .
External controls can overcome the toxic effects of the food environment. Restrained eating is a common finding in normal weight, middle-aged women and in some men 31 . The use of restraint strategies probably explains why obesity is more prevalent in lower socio-economic groups. The stigma of obesity weighs heavily on upwardly mobile women, who thus restrain eating to maintain lower weight.
Predicting those at higher risk of shifting from the preoverweight category to the overweight category would help focus our prevention strategies. In addition to socio-economic status, a family history of overweight, multiple births, birth to a diabetic mother, cessation of smoking, recent marriage, and a few metabolic variables may be predictive 32, 33 . Individuals in the higher risk group can be encouraged to maintain a stable body weight by increasing physical activity and/or by reducing fat and calorie intake.
When primary prevention fails, treatment and secondary prevention become the order of the day. These techniques have been outlined by Aronne, in this Controversy, and in more detail in the Handbook of Obesity 34 . At present, a weight loss of 10–15% can be achieved, on average, by behavior therapy 35 , by diets 36 , or by drugs 34 . The plateau in weight after treatment indicates the presence of counter-regulatory mechanisms that have come into play. Agents are needed in new drugs that will overcome the plateau either singly or in combination with other drugs.
Should we treat obesity at all, given the high failure rates of treatment? Obesity is a chronic, stigmatized disease. Although it has many causes, it is rarely cured. Our treatments are thus palliative, and as with most chronic diseases, treatments only work when used. When treatment for obesity is terminated, patients regain weight, as expected when any effective treatment ends. It is not that the treatment didn’t work when used, but that it is no longer being used. Blood pressure won’t stay down when antihypertensive drugs are stopped and neither will body weight. For individuals at risk from their obesity a strategy of long-term therapy is needed. Because weight regain is slow following weight loss, intermittent therapy may be preferable to continuous therapy.
The introduction of orlistat, the first nonappetite suppressant approved for the treatment of obesity, may be a harbinger of things to come (37). Just as the introduction of thiazides in 1958 was followed by a wide ranging set of new drugs for treatment of hypertension, so the introduction of orlistat in 1998 may be a harbinger of new drugs to come, drugs we can use for treatment and secondary prevention when primary prevention fails.
|
Footnotes |
|---|
|
References |
|---|
|
TopIntroductionReferences |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
