The Metabolic Syndrome and Obesity

307 Pages·2007·2.932 MB·English

by  George A. Bray MD (auth.)

The Metabolic Syndrome and Obesity
The Metabolic
Syndrome and Obesity
by
George A. Bray,
MD
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge, LA
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Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1
eISBN: 978-1-59745-431-5
Library of Congress Cataloging in Publication Data
Bray, George A.
The metabolic syndrome and obesity/ by George A. Bray.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-802-7 (alk. paper)
1. Obesity. 2. Metabolic syndrome. I. Title.
[DNLM: 1. Obesity. 2. Metabolic Syndrome X. WD 210 B827o 2007]
RA645.O23B73 2007
616.3'98--dc22
2006024452
Introduction
Thirty years ago, I published my first monograph on obesity (Bray, 1976). Many things have
changed in these 30 years, but many have remained the same. Preparation of The Metabolic
Syndrome and Obesity has given me a chance to survey the changes to the field and to present an
update of the scientific information. In retrospect, I conclude that a major component of the
current “epidemic” of overweight is not medical, not genetic, not psychological, and will not be
effectively treated by “lifestyle” changes that require individual choices.
We are all influenced by the prices of the goods we buy. With the reduction in food prices and
distortion of commercially profitable products resulting from federal subsidies of corn, sugar,
and rice, the food industry has been able to produce cheap, good-tasting, energy-dense foods and
can sell them cheaply in large portion sizes. In contrast, foods like fruits and vegetables receive
little in the way of subsidies, and are thus more expensive; thus we buy less. Providing more
“healthy” food alternatives, as some advocate, will put items with “higher costs” on the shelves
and is, in my view, unlikely to alter consumer choices as long as good-tasting, energy-dense foods
remain cheap.
HISTORICAL CONTEXT FOR OBESITY
Obesity was already a problem before my first monograph was published. Between the
writing of that monograph and The Metabolic Syndrome and Obesity, I was fortunate enough
to find a short book in French, written by an American from Cincinnati named Worthington.
The book summarized the history of obesity up to 1875 (Worthington, 1875). Obesity as a
clinical problem has been described in medical writings from the Egyptian, Babylonian, Chinese,
Indian, Meso-American, and Greco-Roman medical traditions (Bray, 2004). Causes for
obesity were proposed and many treatments suggested. However, the problem is still with us,
meaning that we neither understand it nor have effective therapy for its treatment. This state-
ment also applies to the interval between my first monograph and this book. We have greatly
increased our knowledge, as I outline here, as well as our treatments, yet at this writing the
problem continues to get worse.
Numerous books dealing with obesity have been published. The first books dedicated solely
to the subject of obesity in the English language were published in 1727 (Short, 1727) and 1760
(Flemyng, 1760). These volumes were followed by books in French, German, and many other
languages during the next two centuries, until the first American monograph dealing with obesity
was published by Rony (1940).
By the time Rony wrote his book, the basic concept of energy conservation and metabolism
had been well established. Just prior to the French Revolution, Lavoisier (1789) had clearly
confirmed that metabolism was similar to a slow oxidation and that more energy was consumed
by human beings during exercise and after a meal. Some 50 years later, the Law of Conservation
of Energy (First Law of Thermodynamics) was clearly stated independently by two Germans,
Hermann von Helmholtz and Robert Mayer. Their work and the calorimeter developed earlier by
Lavoisier stimulated the American Wilbur Atwater to develop the first effective human respira-
v
vi Introduction
tion calorimeter and to show that the Law of Conservation of Energy applied to human beings as
it did to other animals.
While all of this basic science was developing, the first popular diet, a high-protein diet, was
published in Great Britain in 1863 by William Banting in a small pamphlet titled “Letter
on Corpulence, Addressed to the Public” (Banting, 1863). His publication excited the same
fervor as some of the modern popular diet books that are reviewed in The Metabolic Syndrome
and Obesity.
Another important contribution to the science of obesity from the era prior to World War II was
the recognition that it could be caused by many distinct diseases. The first clear-cut examples were
the presence of hypothalamic tumors that produced overweight, and are often associated with
visual problems and endocrine dysfunction. Shortly afterward, Harvey Cushing (1912) showed
that a pituitary tumor could also produce weight gain.
Finally, the life insurance industry has done its best to convince the public, based on its
analysis of life insurance data, that being overweight was dangerous to health and tended to
shorten life span. Beginning in the early 20th century, the life insurance industry published a
number of studies making this point and showing that even modest increases in excess weight
were associated with shortening of life span over many years.
LESSONS LEARNED ABOUT OBESITY
IN THE PAST 30 YEARS
The National Institutes of Health (NIH) is an evolving group of institutes designed to combat
specific problems. In the late 1960s, the Fogarty International Center for Preventive Diseases was
formed in honor of Congressman Fogarty, a Congressional Representative from the State of
Rhode Island who had been a long-time and vocal supporter of expanded support for the NIH. One
of the first activities of this new center was to organize a series of conferences on preventive
medicine. The second of these conferences was on “obesity” because it was perceived to be a
major public health issue, even in 1970. This conference was held at NIH in 1973, and the
proceedings published in 1975.
The impetus to the field from the Fogarty Conference on Obesity led to the first in a series of
international congresses on obesity. The first of these was held in London in 1974 and others were
held at 3-year intervals until 1986 and then at 4-year intervals since. In addition to the develop-
ment of these international meetings came the publication of the first volume of International
Journal of Obesity in 1977.
The first edition of my monograph entitled The Obese Patientwas published in 1976, and
provided for me an opportunity to survey the field in which I had been working. At the same
time, and without adequate recognition at the time, US agricultural policies were undergoing
changes that made some food products cheaper. It was also the time when the “isomerase”
process was developed that allowed the starch from corn to be converted to “fructose,” thus
producing high-fructose corn syrup, which is cheap to make and has displaced much of the
sucrose used in foods and essentially all of the sucrose used to sweeten soft drinks and fruit
drinks. As food prices fell, they represented a smaller fraction of household budget allowing
more people to eat out and to enjoy the tasty, energy-dense foods provided by the increasing
number of fast-food outlets.
The US government has been surveying the weight status of the American public in periodic
surveys beginning in 1960. Between 1960 and the time of my first monograph in 1976, there had
been a slow rise in the prevalence of obesity, which was comparable to the increase from other
Introduction vii
figures dating back to the Civil War in the 19th century. Between the survey completed between
1976 and 1980 and the next one dating from 1988 to 1994, the prevalence of obesity began to rise
more rapidly. This increased rate at which people are becoming overweight has led some to label
this as an “epidemic.”
The major biological advance since 1976 has been the discovery of leptin. This peptide is
produced in fat cells. Its absence produces massive obesity as found in the leptin-deficient,
genetically obese ob/ob mice and in leptin-deficient human beings. Defects in the leptin recep-
tor are responsible for three other varieties of animal obesity (fatty rat, Koletsky rat, and the
diabetes mouse). Similar defects have been shown to produce obesity in human beings. In
addition to the leptin-related genes, the other genes that produce obesity in animals have been
shown to play a role in human obesity. One gene in particular, the one that encodes for the
melanocortin-4 receptor, has been found to be defective in up to 5% of markedly overweight
youngsters. This is one of the most frequent genetic causes of a chronic human disease yet
reported.
Just prior to the Fogarty Center Conference in 1973, a report appeared showing that behavior-
modification strategies could be used to treat overweight subjects. As this technique was explored
in detail, it became one of the three pillars, along with diet and exercise for treatment of over-
weight people. Because of the response to behavioral strategies, obesity has been labeled a
lifestyle disease. Efforts have been made to adapt these behavioral techniques for prevention of
weight gain at the population level, but the effectiveness has been disappointing, to say the least.
Behavior strategies are cognitive strategies, in that they require obese individuals to do something
active—diet, exercise, and modify the way they live. As the literature clearly shows, these cog-
nitive strategies do not translate well in preventive studies, and the weight that is initially lost
using them is usually regained.
One of the most striking developments of the last 30 years has been the internet. This procedure
for communication has now been applied to deliver behavioral management of obesity and offers
promise of further important additions in the future.
The alternative to the cognitive approaches of lifestyle intervention is the use of noncognitive
strategies—strategies that do not require continuing individual involvement. One example is
fluoride used for dental caries. When fluoride was added to the water supply, dental caries were
dramatically reduced without activity of the individual. One noncognitive strategy would be to
use the fact that human beings are price-sensitive, and that using pricing strategies enhances the
choice of appropriate foods.
At the time of my first monograph, the fat cell was viewed as a cell whose primary respon-
sibility was the storage of fat. That view has now dramatically changed. With the discovery of
leptin, it became clear that the fat cell had a much more significant function. Fat cells are part
of the largest endocrine tissue in the body. They produce numerous peptides, which are released
into the circulation and act on other cells. Among these are cytokines, peptides involved in
regulating blood pressure, cell growth, regulation of triglyceride, metabolism, and blood clot-
ting.
The past 30 years has also seen a plethora of new drugs introduced into the treatment of many
diseases. One consequence of this new armamentarium is that some of these medications produce
weight gain. One clear message for physicians who see overweight patients is to evaluate whether
they are taking medications that produce weight gain.
Central adiposity as a risk factor for health was initially identified nearly 100 years ago, but
it wasn’t until 1982 that it became widely appreciated that people with central adiposity were at
risk for diabetes and heart disease. Waist circumference has become the standard for assessing
viii Introduction
central adiposity. Increased waist circumference is also a criterion for the diagnosing the meta-
bolic syndrome—a syndrome that is composed of a number of cardiovascular and diabetes risk
factors, including high blood pressure, impaired fasting glucose, low levels of high-density
lipoprotein cholesterol, and high levels of triglycerides.
Recently, the duration of sleep has been recognized as a factor related to obesity. Children and
adults who sleep only short periods of time are more likely to be overweight. Metabolic studies
provide a basis for understanding the changes produced by sleep.
Several prospective multicenter trials have shown that diets can influence disease risk. The
Dietary Approaches to Stop Hypertension (DASH) diet trial compared the effect of three diets on
blood pressure. One diet was the standard American diet, a second was a diet enriched with fruits
and vegetables aimed at increasing magnesium and potassium levels to the 75th percentile of
normal. The third diet—the DASH or Combination Diet—was enriched with fruits, vegetables,
low-fat dairy products, but also had lowered total fat intake, more fiber, higher protein from
vegetable sources, and reduced intake of calorically sweetened beverages and other sweets. Blood
pressure was significantly reduced in people following the DASH diet. Another large clinical trial
showed that a lifestyle-intervention program with reduced fat and exercise could significantly
delay the onset of diabetes in people with impaired glucose tolerance (The Diabetes Prevention
Program).
Obesity remains a stigmatized condition. Prejudice and dislike for the obese individual are
commonplace. The efforts, particularly of women, to lose weight cost billions of dollars per year.
This is captured in this poem from Ogden Nash:
The human body is composed
of head and limbs and torso
Kept slim by gents
At great expense
By ladies even more so.
As the prospective studies described here indicate, weight loss of modest degrees (5–10%) can
produce a significant reduction in risk factors and thus a significant clinical benefit. In addition
to this clinical benefit from weight loss, there is a self-image or cosmetic benefit. Weight loss
improves quality of life. When the degree of weight loss is not sufficient to produce a cosmetic
benefit from the patient’s perspective, the patient may not be willing to pay the cost and continue
the effort needed to maintain the clinical benefit that is evident to the physician.
Surgery for obesity has its roots in the 1960s, but the current popularity is the result of the
lowered risk related to the use of laparoscopic techniques. Using laparoscopy for surgical treat-
ment of the very overweight patient has reduced the risk and increased the number of treated
patients. It is estimated that in 2005 more than 100,000 had this surgery. The mortality has been
reduced and many of the complications associated with open surgical techniques have been
reduced.
It is against this background of immense change over 30 years that I offer this new volume The
Metabolic Syndrome and Obesity for your consideration.
George A. Bray, MD
REFERENCES
Banting, W. (1863). Letter on corpulence, addressed to the public. London: Harrison and Sons.
Bray, G. A. (1976). The Obese Patient: Major Problems in Internal Medicine. Philadelphia: WB Saunders.
Introduction ix
Bray, G. A. (2004). Historical framework for the development of ideas about obesity. In G. Bray & C. Bouchard (Eds.),
Handbook of Obesity: Etiology and Pathophysiology. New York, Marcel Dekker.
Cushing, H. W. (1912). The pituitary body and its disorders. Clinical states produced by the disorders of the hypophysis
cerebri. Philadelphia: J. B. Lippincott.
Flemyng, M. (1760). A discourse on the nature, causes, and cure of corpulency. Illustrated by a remarkable case. Read
before the Royal Society November 1757. London: L. Davis and C. Reymers.
Rony, H. R. (1940). Obesity and Leanness. Philadelphia: Lea & Febiger.
Short, T. (1727). A discourse concerning the causes and effects of corpulency together with the method for its preven-
tion and cure. London: J. Roberts.
Worthington, L. S. (1875). De l’obesite. Etiologie, therapeutique et hygiene. Paris: E. Martinet.
Contents
Introduction............................................................................................................................................v
Part I. The Problem
1. Definitions and Prevalence.....................................................................................................3
2. How Do We Get Fat?: An Epidemiological and Metabolic Approach.................................31
3. Costs, Pathology, and Health Risks of Obesity
and the Metabolic Syndrome...........................................................................................67
4. Natural History of Obesity: Differential Diagnosis,
Clinical Types, and Age-Related Changes..........................................................................93
Part II. The Solutions
5. Evaluation, Prevention, and Introduction to Treatment ..............................................123
6. Diet..........................................................................................................................................147
7. Behavior Modification.........................................................................................................173
8. Physical Activity and Exercise in the Obese...................................................................185
9. Pharmacological Treatment of the Overweight Patient................................................203
10. Should We Treat the Metabolic Syndrome
or Its Components? .........................................................................................................257
11. Surgical Treatment for the Overweight Patient .............................................................273
Index..................................................................................................................................................... 291
xi