Obesity - Good health

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10 Δεκ 2013 (πριν από 3 χρόνια και 11 μήνες)

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1


OBESITY

Obesity is a substantial public
-
health crisis in the United States and in the rest of
the developed world. The prevalence is increasing rapidly in numerous developing
nations worldwide. This growing rate represents a pandemic that needs urgent
attention if its potential morbidity, mortality, and economic tolls are to be avoided.

The image below shows central nervous system neurocircuitry for satiety and
feeding cycles.



Central nervous system neurocircuitry for satiety and feeding cycles.

2



Th
e annual cost of managing
obesity

in the United States alone amounts to
approximately $100 billion, of which approximately $52 billion are direct costs of
healthcare. These co
sts amount to approximately 5.7% of all US health
expenditure. The cost of lost productivity due to
obesity

is approximately $3.9
billion, and another $33 billion is spent an
nually on weight
-
loss products and
services.

Body fat percentage, body mass index, skin thicknesses, and
anthropomorphic measures

Obesity represents a state of excess storage of body fat. Although similar, the term
overweight is puristically defined as an
excess body weight for height. Although
men have a body fat percentage of 15
-
20%, women have approximately 25
-
30%.
[1]
Because differences in weight among individuals are only partly due to variat
ions
in body fat, body weight is a limited, though easily obtained, index of obesity.

The body mass index (BMI), also known as the Quetelet index, is used far more
commonly than body fat percentage to define obesity. BMI is closely correlated
with the deg
ree of body fat in most settings. BMI = weight/height
2
, where weight is
in kilograms and height is in meters.

The body fat percentage can be estimated by using the Deurenberg equation, as
follows: body fat percentage = 1.2(BMI) + 0.23(age)
-

10.8(sex)
-

5.
4, where age is
in years and sex is 1 for male and 0 for female. This equation has a standard error
of 4% and accounts for approximately 80% of the variation in body fat.

Although the BMI is typically closely correlated with percentage body fat in a
curvil
inear fashion, some important caveats to its interpretation apply. In
mesomorphic (muscular) persons, BMIs that usually indicate overweight or mild
obesity may be spurious, whereas in some persons with sarcopenia (especially
among persons of Asian descent)
, a typically normal BMI may conceal underlying
excess adiposity characterized by increased percentage fat mass and reduced
muscle mass.

In view of these limitations, some authorities advocate a definition of obesity based
on percentage body fat. For men,

percentage body fat greater than 25% defines
obesity, and 21
-
25% is borderline. For women, over 33% defines obesity, and 31
-
33% is borderline.

Taller children generally tend to be more obese than shorter peers, are more
insulin
-
resistant, and have increas
ed leptin levels.
[2]

3


Other indices used to estimate the degree and distribution of obesity include the 4
standard skin thicknesses (ie, subscapular, triceps, biceps, suprailiac) and various
anth
ropometric measures, of which waist and hip circumferences are the most
important.

Classifications and definitions of obesity

Although several classifications and definitions for degrees of obesity are accepted,
the most widely accepted is the World Health

Organization (WHO) criteria based
on BMI. Under this convention for adults, grade 1 overweight (commonly and
simply called overweight) is a BMI of 25
-
29.9 kg/m
2
. Grade 2 overweight
(commonly called obesity) is a BMI of 30
-
39.9 kg/m
2
. Grade 3 overweight
(c
ommonly called severe or morbid obesity) is a BMI greater than or equal to 40
kg/m
2
.

The surgical literature often uses a different classification to recognize particularly
severe obesity. In this setting, a BMI greater than 40 kg/m
2

is described as sever
e
obesity, a BMI of 40
-
50 kg/m
2

is termed morbid obesity, and a BMI greater than
50 kg/m
2

is termed super obese.

The definition of obesity in children involves BMIs greater than the 85th
(commonly used to define overweight) or the 95th (commonly used to d
efine
obesity) percentile, respectively, for age
-
matched and sex
-
matched control
subjects.

Comorbidities associated with obesity

Apart from total body fat mass, accumulating data suggest that regional fat
distribution substantially affects the incidence of

comorbidities associated with
obesity.
[3]
High abdominal fat content (including visceral and, to a lesser extent,
subcutaneous abdominal fat) is strongly correlated with worsened metabolic and
c
linical consequences of obesity. As a result, android obesity, which is
predominantly abdominal, is more predictive of adipose
-
related comorbidities than
gynecoid obesity, which has a relatively peripheral (gluteal) distribution. See
image below.


4


5


Comorbidities of obesity.


Waist circumferences greater than 94 cm in men and greater than 80 cm in women
and waist
-
to
-
hip ratios greater than 0.95 in men and greater than 0.8 in women are
the thresholds for significantly increased potential cardiovascular risk.
Circumferences of 10
2 cm in men and 88 cm in women indicate a markedly
increased potential risk requiring urgent therapeutic intervention; these are the
thresholds used in the Adult Treatment Panel III (ATPIII) definition of the
metabolic syndrome.

A study by Losina et al ex
plored the association of obesity and knee
osteoarthritis.
[4]
The study found that a substantial number of quality
-
adjusted life
-
years were lost due to knee osteoarthritis and obesity, most notab
ly among black
and Hispanic women.

An elevated BMI during adolescence (within the range currently considered
normal) strongly associates with the risk of developing obesity
-
related disorders
later in life.
[5]
Although the BMI closer to onset of diabetes predicts risk of
diabetes, elevated BMI both during adolescence and adulthood strongly predict the
risk of CAD later in life. This observation lends support to the notion that process
of atherogene
sis CAD begins earlier than the manifestation of diabetes.

Obesity is associated with a host of potential comorbidities that significantly
increase the potential morbidity and mortality associated with the condition.
Although no cause
-
and
-
effect relations
hip is exhaustively demonstrated for all
these comorbidities, amelioration of these conditions after substantial weight loss
suggests that obesity probably plays an important role in their development.

Pathophysiology

The pathogenesis of obesity is far more complex than the simple paradigm of an
imbalance between energy intake and energy output. Although this concept allows
easy conceptualization
of the various mechanisms involved in the development of
obesity, obesity is far more than the mere result of too much eating and/or too little
exercise. However, the prevalence of inactivity in developed countries is
considerable and relevant. In the Unit
ed States, only approximately 22% of adults
and 25% of adolescents report notable regular physical activity. Approximately
25% of adults in the United States report no remarkable physical activity during
leisure, while approximately 14% of adolescents have

similar reports of inactivity.
See energy balance equation below.

6




Energy balance equation.

7



Two major groups of factors with a balance that variably intertwines in the
development of obesity are genetics, which is presumed to explain 40
-
70% of the
var
iance in obesity, and environmental factors. Although the high prevalence of
obesity in the children of parents who are obese and the high concordance of
obesity in identical twins suggest a substantial genetic component to the
pathogenesis of obesity, the

secular trends of the last few decades, which have
been coincident with changes in dietary habits and activity, also suggest an
important role for environmental factors.

Leptin

Friedman and colleagues discovered leptin (from the Greek word
leptos,

meanin
g
thin) in 1994 and ushered in an explosion of research and a great increase in
knowledge about regulation of the human feeding and satiation cycle. Since this
discovery, neuromodulation of satiety and hunger with feeding has been found to
be far more comp
lex than the old, simplistic model of the ventromedial
hypothalamic nucleus and limbic centers of satiety and the feeding centers of the
lateral hypothalamus. Leptin is a 16
-
kD protein produced predominantly in white
adipose tissue and, to a lesser extent,

in the placenta, skeletal muscle, and stomach
fundus in rats. Leptin has a myriad of functions in carbohydrate, bone, and
reproductive metabolism that are still being unraveled, but its role in body weight
regulation is the main reason it came to prominen
ce.

The major role of leptin in body
-
weight regulation is to signal satiety to the
hypothalamus and, thus, reduce dietary intake and fat storage while modulating
energy expenditure and carbohydrate metabolism to prevent further weight gain.
Unlike the Ob/
Ob mouse model in which this peptide was first characterized, most
humans who are obese are not leptin deficient but rather leptin resistant. Therefore,
they have elevated circulating levels of leptin.

Lieb et al assayed plasma leptin in 818 elderly partic
ipants in the Framingham
Heart Study.
[8]
Leptin levels, which were higher in women, were strongly
correlated with BMI. On follow
-
up (mean, 8 y), it was found that congestive heart
failure had dev
eloped in 129 participants (out of 775 individuals who had been free
of congestive heart failure), a first cardiovascular disease event had occurred in
187 participants (out of 532 individuals who had been free of cardiovascular
disease), and 391 persons h
ad died. The authors' data indicated that higher
circulating leptin levels were associated with a greater risk of congestive heart
8


failure and cardiovascular disease but that leptin did not offer incremental
prognostic information beyond BMI.

Although more

than 90% of human cases of obesity are polygenic, the recognition
of monogenic variants has greatly enhanced our knowledge about the
etiopathogenesis of obesity.
[9]

Epidemiology

Frequency

International

The prevalence of obesity worldwide is increasing, particularly in the developed
nations of the Northern hemisphere, such as the United States, Canada, and most
countries of Europe. Available data from the Multinational Monitoring of Trends
and Determinant
s in Cardiovascular Disease (MONICA) project suggest that at
least 15% of men and 22% of women in Europe are obese.

Similar data now are being reported from many developing countries, particularly
in those in Asia and, to a lesser extent, those in Africa.

Reports from countries such
as Malaysia, Japan, Australia, New Zealand, and China detail an epidemic of
obesity in the past 2
-
3 decades. Data from the Middle Eastern countries of Bahrain,
Saudi Arabia, Egypt, Jordan, Tunisia, and Lebanon, among others, in
dicate this
same disturbing trend, with alarming levels of obesity often exceeding 40% and
particularly worse in women than in men.

Data from the Caribbean and from South America also highlight similar trends.
Although data from Africa on this issue are sc
ant, a clear and distinct secular trend
of profoundly increased BMIs is clearly observed when people from Africa
immigrate to northwestern hemispheric countries. Comparisons of these indices
among Nigerians and Ghanaians residing in their native countries
with indices in
recent immigrants to the United States show this trend poignantly.

Conservative estimates suggest that as many as 250 million people (approximately
7% of the estimated current world population) are obese. Two
-

to three
-
times more
people th
an this are probably overweight. Although socioeconomic class and the
prevalence of obesity are negatively correlated in most developed countries,
including the United States, this correlation is distinctly reversed in many
relatively undeveloped areas, in
cluding China, Malaysia, parts of South America,
and sub
-
Saharan Africa.

9


Finucane et al conducted a comprehensive, constructive study that revealed
growing global trends in BMI. This study may serve as wake
-
up call and initiate
large
-
scale interventions in

an effort to combat increasing body weight and
associated adverse health consequences.
[12]

Mortality/Morbidity

Some evidence suggests that, if unchecked, trends in obesity in the United States
may be associated with overall reduced longevity of the population in the next few
years. Data also show that obesity is associated with an increased risk and duration
of lifetime disability. Furthermore, obesity in middle age is associated with poor
indic
es of quality of life at old age.

The mortality data appear to have a
U

-

or
J

-
shaped conformation in relation to
weight distribution.
[14]
However, the degree of obesity (generally indicated by

the
BMI) at which mortality discernibly increases in African Americans and Hispanic
Americans than in white Americans; this observation suggests a notable racial
spectrum and difference in this effect. Underweight was associated with
substantially high ri
sk of death in a study of Asian populations. A high BMI is also
associated with an increased risk of death, except in Indians and Bangladeshis.
[15]

The optimal BMI in terms of life expectancy is

about 23
-
25 for whites and 23
-
30
for blacks. Emerging data suggest that the ideal BMI for Asians is substantially
lower than that for Caucasians. For subjects with severe obesity (BMIs ≥40), life
expectancy is reduced by as much as 20 years in men and by
about 5 years in
women. Coexisting obesity and smoking are associated with even greater risks
than these for premature mortality.

A study by Berrington de Gonzalez et al confirms health advantages of normal
BMI (20
-
24.9) and reinforces that both overweigh
t and underweight have
deleterious consequences

increased death risk.
[16]

Several factors modulate the morbidity and mortality associated with obesity. They
include age of onset and duration of
obesity, severity of obesity, amount of central
adiposity, other comorbidities, sex, and level of cardiorespiratory fitness.

Race

Obesity is a cosmopolitan disease that affects all races worldwide. However,
certain ethnic and racial groups appear to be pa
rticularly predisposed. The Pima
Indians of Arizona and other ethnic groups native to North America have a
particularly high prevalence of obesity. In addition, Polynesians, Micronesians,
10


Anurans, Maoris of the West and East Indies, African Americans in No
rth
America, and the Hispanic populations (both Mexican and Puerto Rican in origin)
in North America also have particularly high predispositions to developing obesity.

Secular trends clearly emphasize the importance of environmental factors
(particularly
dietary issues) in the development of obesity. In many genetically
similar cohorts of the high
-
risk ethnic and racial groups mentioned above, the
prevalence for obesity in their countries of origin might be low, but this rate
considerably changes when such

groups emigrate to the affluent countries of the
Northern hemisphere, where they alter their dietary and activity habits. These
findings form the core concept of the thrifty gene hypothesis that Neal and
colleagues espoused.

See also Mortality/Morbidity
above.

Sex

No significant sex difference is reported in the prevalence of obesity.

Age

The prevalence and age distribution of obesity has substantially changed in the last
2
-
3 decades.

Although the prevalence has remained at 30
-
50% of the adult population

in the
United States, the prevalence in children has increased to 15
-
25%.

As evidenced in secular trends, children and particularly adolescents who are obese
have a high probability of growing to be adults who are obese; hence, the bimodal
distribution o
f obesity portends a large
-
scale obesity epidemic in the next few
decades.

Adolescent obesity poses a serious risk for severe obesity during early adulthood,
particularly in non
-
Hispanic black women. This would call for stronger emphasis
on reduction duri
ng early adolescence specifically targeting groups with greater
risk.
[17]



History

11


In most patients, the presentation is straightforward, with the patient indicating
problems with weight or repeated failure in achieving sustained weight loss.
However, in other cases, the subject may present with complications and/or
associations of obesi
ty.

A full history must include a dietary inventory and an analysis of the subject's
activity level.

Screening questions to exclude depression are vital because this may be a
consequence or a cause of excessive dietary intake and reduced activity.

Becaus
e almost 30% of patients who are obese have eating disorders, screen for
these in the history. The possibility of binging, purging, lack of satiety, food
-
seeking behavior, and other abnormal feeding habits must be identified because
management of these hab
its is crucial to the success of any weight
-
management
program.

Also, determine if any of the previously mentioned comorbidities have occurred,
and include questions to exclude the possible and rare secondary causes of obesity.
See image below.


12



Seconda
ry causes of obesity.


When asking patients about their history, investigate whether the rest of the
patient's family has weight problems, inquire about the patient's expectations, and
estimate the patient's level of motivation.

Comorbidities related to

obesity include the following
:



Cardiovascular
-

Essential
hypertension
,
coronary artery
disease
,
[18]
left
ventricular hypertrophy,
cor pulmonale
, obesity
-
associated
cardiomyopathy
,
accelerated
atherosclerosis
,
pulm
onary hypertension

of obesity



CNS
-
Stroke
,
idiopathic intracranial hypertension
,
meralgia paresthetica



GI
-

Gall bladder disease (
cholecystitis
,
cholelithiasis
), nonalcoholic
steatohepatitis (NASH),
fatty liver

infiltration, reflux
esophagitis



Respiratory
-
Obstructive sleep apnea
,
[19]
obesity hypoventilation syndrome

(Pickwickian syndrome), increased predisposition to respiratory infections,
increased incidence of bronchial
asthma



Malignant
-

Association with endometrial, prostate, gall bladder, breast,
colon, and, possibly, lung cancer
[20]



Psycholo
gic
-

Social stigmatization, depression



Orthopedic
-
Osteoarthritis
, coxa vera, slipped capital femoral epiphyses,
Blount disease and
Legg
-
Calvé
-
Perthes disease
, chronic lumbago



Metabolic
-
Insulin resistance
,
hyperinsulinemia
,
type 2 diabetes mellitus

(see image below), dyslipidemia (characterized by high total cholesterol,
high triglycerides, normal or elevate
d low
-
density lipoprotein, and low high
-
density lipoprotein)


13



Simplified scheme for the pathophysiology of type 2 diabetes mellitus.



Reproductive
-

Anovulation, early puberty, infertility,
hyperandrogenism

and
polycystic ovaries

in women,
hypogonadotropic hypogonadism

in men



Obstetric and perinatal
-
Pregnancy
-
related hypertension
,
fetal macrosomia
,
pelvic dystocia
[21]



Surgical
-

Increased surgical risk and postoperative complications, including
wound infection
,
deep venous thrombosis
,
pulmonary embo
lism
, and
postoperative pneumonia



Pelvic
-

Stress incontinence



Cutaneous
-

Intertrigo (bacterial and/or fungal), acanthosis nigricans,
hirsutism
, increased risk for celluliti
s and carbuncles



Extremity
-

Venous varicosities, lower extremity venous and/or lymphatic
edema



Miscellaneous
-

Reduced mobility, difficulty maintaining personal hygiene

Physical

In the clinical examination, measure anthropometric parameters and perform the
standard, detailed examination required in evaluating people with any chronic
multisystemic disorder, such as obesity. Waist and hip circumferen
ce are useful
14


surrogates in estimating visceral fat. Serial tracking of these measurements helps in
estimating the clinical risk over time.

Neck circumference is predictive of a risk of sleep apnea, and its serial
measurement in the individual patient is
clinically useful for risk stratification.
[19]

In the skin examination, include a search for hirsutism in women, intertriginous
rashes, acanthosis nigricans, and possible contact dermatoses.

A
detailed cardiac and respiratory evaluation is crucial to exclude cardiomegaly
and respiratory insufficiency.

In the abdominal examination, attempt to exclude tender hepatomegaly (which
may suggest nonalcoholic steatohepatitis [NASH]) and distinguishing th
e striae
distensae from the pink and broad striae that suggest cortisol excess.

When examining the extremities, search for joint deformities (eg, coxa vara),
evidence of osteoarthrosis, and any pressure ulcerations.

Causes

The etiology of obesity is multifactorial.

Among the facets to be considered in the development of obesity are the following:



Metabolic factors



Genetic factors



Level of
activity



Behavior



Endocrine factors



Race, sex, and age factors



Ethnic and cultural factors



Socioeconomic status



Dietary habits



Smoking cessation



Pregnancy and menopause



Psychologic factors



History of gestational diabetes



Lactational history in mothers

Seco
ndary causes of obesity may include the following (see also the image below):


15


Secondary causes of obesity.


Diagnostic Considerations



Adiposa dolorosa (Dercum disease)



Partial lipodystrophies associated with localized lipohypertrophy

Mesomorphic body
states, as seen in body builders and people in related
occupations (eg, professional wrestling) may be associated with elevated BMIs
because of increased muscle mass rather than excess adiposity.

Various causes of anasarca may be mistaken as obesity if not

carefully evaluated
clinically.




16


Laboratory Studies

Full lipid panel, at minimum, test of fasting cholesterol, triglycerides,
and high
-
density lipoprotein cholesterol (HDL
-
C) levels

These levels may be normal, or the typical dyslipidemia associated with metabolic
syndrome X may be found.

This is characterized by reduced HDL
-
C, increased low
-
density lipoprotein
cholesterol (LDL
-
C), normal
-
to
-
marginally increased total cholesterol, and
elevated fasting triglyceride concentrations.

Hepatic panel

This test is expected to yield normal results,

but findings may be abnormal (eg,
elevated transaminase levels in the setting of NASH or fatty infiltration of the
liver).

Thyroid function tests

The results are typically normal, but checking them to detect primary
hypothyroidism (characterized by incre
ased serum thyrotropin and normal or
reduced levothyroxine and/or triiodothyronine levels) is worthwhile.

Screening with a serum thyrotropin level is usually sufficient. Of importance,
hypothyroidism itself rarely causes more than mild obesity.

For screen
ing purposes, 24
-
hour urinary free cortisol test

This test is needed only when Cushing syndrome or other hypercortisolemic states
are clinically suspected.

Approximately 4% of patients with Cushing syndrome have normal urinary free
cortisol values.

Fastin
g glucose and insulin test

Obesity is associated with insulin resistance, though these levels are normal in
many subjects who are obese.

In other people, insulin levels may be elevated.

17


In those with impaired glucose tolerance, the fasting serum glucose l
evel is
elevated to higher than 100 mg/dL.

Procedures

Among the various procedures relevant to the treatment of patients who are obese
are procedures t
o estimate the degree of visceral and subcutaneous fat.

These procedures include the standard anthropometric measurements and caliper
-
derived estimates of skin thickness.




Medical Care

Although obesity in itself is associated with increased morbidity and mortality,
massive poorly monitored weight loss and/or weight cycling can have equally dire
consequences. Among the important potential complications to watch out for in the
setting of w
eight loss are cardiac arrhythmias; electrolyte derangements, of which
hypokalemia is the most important; hyperuricemia; and psychologic sequelae,
including depression and the development of eating disorders (particularly binge
-
eating disorders).

The 3 ma
jor phases of any successful weight
-
loss program are (1) a preinclusion
screening phase; (2) a definitive weight
-
loss program; and (3) a maintenance
phase, which can conceivably last for the rest of the subject's life but which must
last for at least 2 yea
rs after the weight
-
loss program is completed.

Weight loss as medical treatment

A reasonable goal for weight
-
loss in the setting of a medical treatment program is
approximately 0.9
-
1.5 kg/wk. The concept that the weight
-
loss goal for each
subject must be individualized and cannot be unilaterally based on standard
weight
-
for
-
height nor
ms is becoming increasingly apparent.

One must consider the family's weight, as well as the patient's weight and cultural,
ethnic, and racial background in setting individualized goals of weight loss. In a
study of approximately 200 obese black women, the

Obesity Reduction Black
Intervention Trial (ORBIT) investigated whether greater weight loss could be
achieved with a culturally adapted weight
-
loss program than with a more general
health program.
[22]

The women were randomly divided into a general health program or a 6
-
month
culturally adapted program aimed at altering the women's dietary and physical
18


activity patterns (followed by 1 year of maintenance intervention). Women in the
latter group l
ost significantly more weight than did participants in the general
program, although the report also found that, despite this success, the average
weight loss in the culturally adapted program was still relatively modest and that
the amount of weight loss
varied greatly among the women in the program.

Like all chronic medical conditions, effective management of obesity must be
based on a partnership between a highly motivated patient and a committed team
of health professionals, including the physician, ps
ychologists or psychiatrist,
physical and exercise therapists, dietitians, and other subspecialists, depending on
the comorbidities of the individual patient.

Results of weight
-
loss management

Results of most weight loss management programs are dismal. On

average,
participants in the best weight
-
loss programs lose approximately 10% of their body
weight, but people generally regain two thirds of the weight lost within a year, and
they regain almost all of it within 5 years.

When defined as sustained weight

loss over a 5
-
year follow
-
up period, the success
of even the best medical weight
-
loss programs is next to nil. Most available data
indicate that, irrespective of the method of medical intervention, 90
-
95% of the
weight lost is regained in 5 years.

In gen
eral, body weight and body fat generally tenaciously regulated. Available
data suggest that a loss of approximately 10% of body weight in subjects who are
obese (BMI < 40) is associated with virtually maximal benefits regarding obesity
-
elated comorbidities
; therefore, further attempts at weight loss beyond this level
are generally spurred by cosmetic considerations that may be not only unrealistic
but also potentially dangerous. This possibility is the basis of a shift in paradigms
in the medical management

of obesity from a goal of massive weight loss to a goal
of maintaining the highest weight possible while still eliminating obesity
-
related
comorbidities or reducing them to minimum.

A study by Rock et al found that a structured weight loss program resulte
d in
greater risk reduction than usual care.
[23]

Childhood obesity

For childhood obesity,
[24, 25, 26]
the goal is to reduce the rate
of weight gain to fit the
profile expected based on normal growth curves. The intent here is not to cause
weight loss.

19


The basic principles of management include (1) modifying diet, (2) increasing
appropriate physical activity and exercise, (3) reducing t
ime spent in sedentary
activities (eg, watching television), and (4) modifying behavior.

Added to these principles is medication therapy. However, such therapy is still
rudimentary in the management of pediatric obesity, and close combination with
all the

aforementioned modalities is required to achieve substantial and sustained
weight loss. At the present, orlistat is the only medication the US Food and Drug
Administration (FDA) has approved for use as an adjunct for weight loss in
adolescents.

Dietary p
rograms

Starvation is a caloric intake of less than 200 kcal/d and is not medically indicated.
Starvation is potentially dangerous and can lead to clinically significant starvation
ketosis; electrolyte derangements; vitamin, mineral, and other micronutrien
t
deficiencies; and a marked potential for morbidity and mortality. Starvation is not
validated as an effective method of achieving substantial and sustained weight loss.

Achieving a caloric deficit is still the most important component to achieving
susta
ined weight loss. However, the considerable variance in individual energy
expenditures and compliances to calorie
-
deficient plans make it difficult to reliably
predict how much weight an individual subject may lose.

Among the caveats are the fact that ene
rgy expenditure is related to body weight;
about 22 kcal/kg of energy required for basal maintenance of 1 kg of weight in a
typical adult. Therefore, obese subjects tend to reduce their energy expenditure as
they lose weight, dampening the effect of calori
c deficits as weight loss progresses.

Presumably because of their greater lean mass proportions, men tend to lose more
weight than women do when caloric deficits are similar.

Because of their lowered energy expenditure, older subjects have increased
diff
iculty is achieving sustained weight loss. The estimated reduction in energy
expenditure is 100 kcal per decade after the age of 30 years.

Dennis et al found that in overweight and obese middle
-
aged and older adults on a
hypocaloric diet, drinking water be
fore each main meal aided weight loss. In 48
adults aged 55
-
75 years with a BMI of 25
-
40 kg/m
2
, those who consumed 500 mL
of water prior to each daily meal had a 44% greater decline in weight over 12
weeks than did individuals on a hypocaloric diet without

premeal water
consumption.
[27]

20


Very

low
-
calorie diets

Very

low
-
calorie diets (VLCDs) are best used in an established, comprehensive
program. VLCDs involve reducing caloric intake to 800 kcal/d
or less. When used
in optimal settings, they can achieve weight loss of 1.5
-
2.5 kg/wk, with a total loss
of as much as 20 kg over 12 weeks. No good
-
quality evidence suggests that a daily
calorie intake of less than 800 kcal/d achieves any additional weight

loss.

Use special caution whenever VLCDs are prescribed to children, adolescents, or
elderly subjects. Use is contraindicated in pregnancy and in protein
-
wasting states;
clinically significant cardiac, renal, hepatic, psychiatric, or cerebrovascular
dise
ase; or any other chronic disease. VLCDs are associated with profound initial
weight loss, much of which is from lean mass loss in the first few weeks. However,
this loss rapidly ceases, and weight
-
loss velocity then flattens. Although these diets
associat
ed with notable short
-
term weight loss sometimes less than 15% of
baseline weight and though they are associated with improved blood pressure and
glycemic control, they cannot be sustained longer than 3
-
6 months. Compliance
beyond a few weeks is poor, and
close supervision is required to avoid mishaps.

Unless a long
-
term maintenance calorie
-
deficit program is developed and adhered,
to recidivism after the diet is stopped is rapid. Most subjects quickly regain all the
weight they lose and often gain more.

Among the major complications to monitor are hair loss, skin thinning,
hypothermia
,
cholelithiasis
, and electrolyte derangement. VLCDs have little or no
utility in long
-
term weight management and are probably best used as stop
-
gap
measures before
bariatric su
rgery

or a long
-
term comprehensive weight
-
loss
program in subjects with very severe or morbid obesity and associated
comorbidities (BMI ≥50).

Conventional diets

Conventional diets can be broadly subclassified as (1) balanced, low
-
calorie diets
(or reduced portion sizes), (2) low
-
fat diets, (3) low
-
carbohydrate diets, (4)
midlevel diets (eg, Zone diet in which the 3 major macronutrients [fat,
carbohydrate, protein]

are eaten in similar proportions of 30
-
40%), and (5) fad
diets.

Balanced LCDs or reduced portion sizes diets are the types that dietitians and other
weight
-
management professionals most commonly prescribe. These diets underlie
most of the popular, commer
cial weight
-
loss programs such as those advocated by
Jenny Craig, Weight Watchers, Take Off Pounds Sensibly (TOPs), and Overweight
21


Anonymous. The basic premise involves obtaining a detailed dietary inventory of
the subject, which is used to estimate his or

her mean daily caloric intake.

A reasonable goal for the caloric deficit is based on the new goal for total daily
calories. Meal plans are then devised to provide this total in ≥3 divided meals
throughout the day. Although the meals may be based on regul
ar, everyday foods
(with which strategies for effective reduction of portion sizes become central),
meal
-
replacement shakes, bars, prepackaged meals, frozen entrees, and other meals
also have adequate amounts of the major macronutrients based on the food
p
yramid from the US Department of Agriculture and recommended daily
allowances (RDAs). These sources also have adequate micronutrients and trace
elements. Because alcohol, sodas, most fruit juices, and highly concentrated sweets
are generally calorie dense
and nutrient deficient (empty calories), these are
generally prohibited or reduced to the minimum.

Low
-
calorie diets involve a caloric intake of 800
-
1200 kcal/d and are associated
with a mean weight loss of 0.4
-
0.5 kg/wk, with a total loss of 6
-
8 kg in id
eal
settings. With any low
-
calorie diet, maintaining intake of protein with high
biologic value of ≥1 g/kg is vital to preserve lean body mass. Major potential
complications to watch for include vitamin deficiency, starvation ketosis,
electrolyte derangeme
nts, and cholelithiasis. Although these diets are useful for
short
-
term weight loss, none alone is associated with reliable, sustained weight
loss.

Normal
-
calorie diets involve diets with a caloric intake greater than 1200 kcal/d.
The aim with this type o
f diet is to reduce the caloric intake by 500
-
1000 kcal/d
from the patient's current dietary intake. The suggested composition for the best
-
validated dietary programs are protein intake of 0.8
-
1.5 g/kg of body weight (not to
exceed 100 g/d), 10
-
30% of tota
l calories from fat (preferably ≥90% as
polyunsaturated fat and < 10% as saturated fat), carbohydrate intake of ≥50 g/d,
and water intake of ≥1 L. Ensure that the dietary plan provides adequate
micronutrients and macronutrients based on RDAs.

Low
-
carbohyd
rate diets have become popular in the past few decades, with the
Atkins diet being the most popular. Little rigorous scientific data supports the use
of the Atkins diet. It is a high
-
protein and/or high
-
fat, very
-
low
-
carbohydrate diet
that induces ketosis.

The very low carbohydrate content is critical in inducing
short
-
term weight loss in the first 2
-
4 weeks; this is largely due to fluid
mobilization. Ketone bodies tend to be generated with daily dietary carbohydrate
intake of < 50 g, force sodium diuresis,

which causes most of the short
-
term weight
loss. No robust data about the safety or long
-
term effectiveness of this diet are
available. The premise of the diet is that caloric intake as protein is less prone to fat
22


storage than the equivalent caloric inta
ke as carbohydrate; however, no physiologic
data support this premise.

Data on the long
-
term effects of a high
-
protein in rodents causes concern because
these diets may be associated with a reduced life span and predisposition to
neoplasia.

In 2 randomiz
ed trials weight loss with Atkins
-
type diets were compared with
conventional low
-
fat or balanced calorie
-
deficit diets. Although the Atkins
-
type
diet had the greatest initial weight loss, weight loss became similar within 1 year.
Furthermore, though lipids

did not appear to be deleteriously affected, follow
-
up
was only about 1 year, and noncompliance rates in the Atkins
-
type group was close
to 50%.

The South Beach diet is another low
-
carbohydrate diet. This program is more
liberal than the Atkins diet in i
ts carbohydrate allowance; therefore, compliance
rates are enhanced. The South Beach diet distinguishes between what it considered
to be good and bad carbohydrates on the basis of their glycemic index. Although
the relevance and importance of the glycemic
index is controversial, the diet
encourages increased fiber intake, which is associated with lowered weight even
when total caloric intake is relatively unchanged. Low
-
glycemic index diets plus
modest increase in protein intake are better at helping mainta
in weight loss.
[28]

The National Weight loss database, tracks indices and predictors in subjects with
sustained (≥5 y) weight loss of 15% or greater. The data indicate that sustained
compliance
to diet programs is by far a more important predictor of sustained
weight loss than consistently increased levels of physical activity. Caloric deficits
are more important than any specific composition of dietary macronutrient. When
types of diets are comp
ared, low
-
fat diets are better than low
-
carbohydrate diets in
achieving sustained weight loss (probably because of generally improved
compliance).

Dansinger and colleagues (2005) compared the Zone, Ornish, and Atkins diets and
a typical balanced, calorie
-
restricted (Weight Watchers) diet.
[29]
The Ornish diet,
very
-
low
-
fat diet, and the Atkins diets had the poorest compliance rates. The
researchers observed no significant differences in weight los
s based on the diet.
Compliance and caloric deficits were more important predictors of weight loss and
improvement in cardiovascular risk surrogates than specific dietary composition.
However, a recent study found low
-
carbohydrate and low
-
fat diets equally

efficacious in inducing weight loss but that fuel partitioning may impact
cardiovascular markers differently.
[30]

23


For subjects who decide to use a low
-
carbohydrate diet, they should choose hear
t
-
healthy sources of fat (monounsaturated fats, polyunsaturated fats, and fats rich in
omega 3 fatty acids rather than saturated fat) and protein (fish, nuts, legumes, and
lean poultry rather than pork chops, steak, or mutton).

Exercise programs

Before re
ceiving an exercise
-
program prescription, patients should undergo
screening for cardiovascular and respiratory adequacy. Any clinically significant
anomalies found require full evaluation by appropriate subspecialist physicians,
and only after these issues

are adequately managed and stabilized should an active
exercise program be begun.

Aerobic isotonic exercise is of the greatest value for subjects who are obese. The
ultimate minimum goal should be to achieve 30
-
60 minutes of continuous aerobic
exercise 5
-
7 times per week.

Anaerobic isometric exercise, including resistance training, can be cautiously
added as an adjunct after the aerobic goal described above is achieved.

Exercise is vital to any weight
-
management program because it helps build muscle
mas
s, increasing metabolic activity of the whole
-
body mass. Exercise also helps
reduce body
-
fat proportions and decreases the amount of compensatory muscle
mass loss that is typical in the setting of weight loss. Although most laypersons
may be unable to sust
ain enough regular exercise to achieve weight loss, consistent
moderate exercise is important in maintaining weight and in improving overall
cardiorespiratory fitness.

A study by Goodpaster et al showed that patients with severe obesity who
introduced exer
cise concurrently with or after dietary intervention had significant
weight loss and modification of cardiometabolic risk factors.
[31]
Furthermore, a
study by Hankinson et al indicated that benef
its of exercise in young age may
translate into benefits beyond, particularly in young women.
[32]
This information is
useful for patients and physicians who may be discouraged by the initial inab
ility
of patients to engage in exercise.

A combination of weight loss and exercise is better than either alone in improving
physical fitness.
[33]

Behavioral changes

24


This treatment requires a tra
ined professional to have an in
-
depth discussion with
the patient regarding the changes required, subsequent to a detailed inventory of
the patients' daily activities. This inventory is used to identify activities, cues,
circumstances, and practices that f
avor nonmeal eating and snacking. An
individualized plan to change these practices is then developed in conjunction with
the subject. The effectiveness of this modality depends on both a highly motivated
subject and a dedicated counselor who is willing to
maintain long
-
term follow
-
up.

A sufficient amount of human sleep favorably impacts maintenance of fat
-
free
mass during times of decreased energy intake. On the contrary, insufficient sleep
would undermine the body's ability to limit expansion of fat mass.
A healthy sleep
pattern would be important to harness weight loss benefits from other
interventions.
[34]

A 3
-
month intervention (face
-
to
-
face education sessions) led to significant weight
loss a
nd better health
-
related outcomes in fathers and improved eating and physical
activity among children.
[35]
Involvement of fathers in the weight management of
children needs to be encouraged and further explored.

Medications

Not many medications are available for the treatment of obesity, and those that are
available have minimal long
-
term effectiveness.

The
increasing knowledge that has come on the heels of the discovery of leptin by
Friedman and colleagues in 1994 has spurred a whirlwind of research, with several
potential pharmaceuticals now being evaluated in various phases of clinical trial.

Murray et al
first reported on a sequence variant within the leptin gene that
enhances the intrinsic bioactivity of leptin, leading to reduced weight rather than
obesity.
[36]
This sequence variant within the
leptin gene is associated with delayed
puberty as well.

The major groups of drugs used to manage obesity are (1) centrally acting
medications that impair dietary intake, (2) medications that act peripherally to
impair dietary absorption, and (3) medicatio
ns that increase energy expenditure.

Standards for the development of obesity medications are necessarily high because
most persons who are obese are fairly healthy in the short
-
term and must take these
medications for extended periods (possibly for the r
est of their lives).

The history of obesity medications is replete with numerous disasters that have
taught us caution in the use of this group of medicines.

25


Among the initial medications used for obesity management were amphetamine,
methamphetamine, and

phenmetrazine. These were all withdrawn because of their
high potential for abuse.

Other former antiobesity medications are thyroid hormone (which caused
hyperthyroidism with its attendant sequelae), dinitrophenol (which caused cataracts
and neuropathy),

rainbow pills (which are a mixture of digitalis and diuretics
[which caused deaths from arrhythmias and electrolyte derangements]), aminorex
(which caused pulmonary hypertension), and collagen
-
based VLCDs (which
caused sudden deaths).

D
-
fenfluramine was
withdrawn because of problems with cardiac valvulopathies
and primary pulmonary hypertension (PPH).

Fluoxetine is not approved for use in achieving weight loss, but it has been known
to cause minimal weight loss as an adverse effect, which is sometimes exp
loited.

Fenfluramine, although effectively used in combination with phentermine, was
withdrawn in 1997 (along with D
-
fenfluramine) because of the potential for
adverse cardiac, valvular, and pulmonary hypertensive effects.

The combination of fenfluramine

and phentermine was used in some long
-
term
trials with fair results.

The combination of low
-
dose phentermine and topiramate in conjunction with
office
-
based lifestyle intervention might improve the success rate in the treatment
of obesity.
[37]

Diethylpropion (25 mg 3 times/d [tid]) and phentermine are available in the US for
short
-
term use.

Phendimetrazine (30 mg/d) and benzphetamine (20
-
50 mg tid) are not longer
available in the US.

Mazindol, w
hich was withdrawn from the US market in 2001, was another drug
that was only for short
-
term use (1 mg tid).

Phenylpropanolamine, which was also for short
-
term use (25 mg tid), was recalled
from the US market. Phenylpropanolamine is an alpha
-
adrenoreceptor

agonist.
Some reports suggested a potential association between the use of
phenylpropanolamine and ischemic stroke; therefore, this drug should be used with
caution in elderly individuals and only after carotid atherosclerosis is excluded.

26


Methylphenidat
e is not approved by the FDA for obesity management, although
several anecdotal reports have described it as having variable success for this
purpose.
[38]

Sibutramine (Meridia) is a centrally ac
ting appetite suppressant that inhibits
reuptake of noradrenalin, serotonin, and dopamine.
[39]
The Sibutramine Trial of
Obesity Reduction and Maintenance (STORM) revealed that a 9% weight loss
pe
rsisted for as long as 18 months after the start of therapy. Sibutramine is fraught
with adverse cardiovascular outcomes, and the drug has been withdrawn from the
market in Europe. The US FDA is asking its advisory panel to review sibutramine
safety in lig
ht of the recently published Sibutramine Cardiovascular Outcomes
(SCOUT) trial.
[40]

On October 8, 2010, Abbott and the US Food and Drug Administration (FDA)
announced sibutramine (Meridia) is be
ing withdrawn from the market because of
increased risk of myocardial infarction (MI) and stroke. Europe suspended
sibutramine from the market earlier this year.

The FDA requested the market withdrawal after reviewing data from the
Sibutramine Cardiovascu
lar Outcomes Trial (SCOUT). SCOUT was initiated as
part of a postmarket requirement to look at cardiovascular safety of sibutramine
after the European approval of this drug. The trial demonstrated a 16% increase in
the risk of serious heart events, includi
ng nonfatal MI, nonfatal stroke, the need to
be resuscitated once the heart stopped, and death, in a group of patients given
sibutramine and another given placebo. A very small difference (2.5%) in weight
loss was noted between the placebo group and the gr
oup that received
sibutramine.
[41]

Orlistat is the only FDA
-
approved antiobesity drug on the market. Orlistat
(Xenical) blocks the action of pancreatic lipase, reducing triglyceride digestion
an
d, thus, absorption.
[42]
Two major clinical trials showed sustained weight loss of
9
-
10% over 2 years.

Ephedrine and caffeine are second
-
line options in the medical management of
obesity. They b
oth act by increasing energy expenditure, but they are associated
with the potential for tachycardia, hypertension, and palpitations. These
medications are associated with more weight loss when used in combination than
when used alone. They cause 25
-
40% of

their weight loss by inducing
thermogenesis, but they also decrease food intake, which accounts for 60
-
75% of
the weight
-
loss effect.

27


Although not FDA approved for this purpose, several selective serotonin reuptake
inhibitors (SSRIs; eg, fluoxetine, paro
xetine) may cause anorexia as one of their
major adverse effects. Some of these medications have been used as adjuncts in the
medical management of obesity, with variable success.

Bupropion, which is licensed for use as an antidepressant and in smoking
ce
ssation, is associated with minimal to moderate weight loss.
[43]
Preliminary
reports have suggested similar findings with venlafaxine.

Topiramate, licensed as an adjunctive antiepileptic agent,
was associated with
profound weight loss of as much as 15
-
18% of the baseline weight. The amount of
weight loss appears to be greater with greater baseline weights. The exact
mechanism of this effect is being actively investigated. Although the degree of
e
fficacy is exciting, the propensity for adverse effects, especially CNS effects such
as drowsiness, paresthesias, memory loss, and confusion, is concerning. Doses for
weight management are lower than those for seizure management (usually 25
-
100
mg/day in d
ivided doses). Doses >200 mg/d are rarely tolerated when administered
for weight loss. Topiramate does not have an FDA
-
approved indication for weight
loss at this time.
[44]

The central cannabino
id system and feeding disorders

The importance of the central cannabinoid system in the understanding and
management of feeding disorders has increased.
[45, 46, 47, 48]

In particular, activation of the cannabinoid type 1 (CB1) receptor is associated with
increased appetite and appears to be the basis for the effectiveness of dronabinol in
enhancing diet in AIDS and other wasting syndromes. CB1 antagonists showed
great pot
ential for weight management in several human trials.

Rimonabant, the most
-
developed CB1 antagonist, caused mean weight loss of 3
-
6
kg over 1
-
year follow
-
up at doses of 5
-
20 mg/d. Adverse effects, which were most
prevalent at high doses, included dizzines
s, mood swings, headaches, nausea,
vomiting, and diarrhea. Rimonabant may obtain FDA approval as an adjunct for
weight loss in the next 2
-
3 years based on the accumulating data from phase 3
trials of human obesity.

Investigational drugs

Agents in early ph
ases of investigation that may yet prove of use include ghrelin
antagonists, alpha
-
MSH analogs, enterostatin, neuropeptide YY antagonists, beta3
-
adrenergic agonists, and various nutraceuticals and herbal products (including the
28


extract from the African cac
tus
Hoodia gordonii
, which may cause clinically
significant appetite suppression).

Metformin does not have an indication for obesity, but it was useful in preventing
diabetes and improving insulin resistance in conditions such as polycystic ovary
syndrome

[PCOS]. Its use was associated with weight neutrality or mild weight
loss.
[49]

Gadde and colleagues reported that randomized use of the antiepileptic drug
zonisamide in a cohort of 60 obese sub
jects was associated with a weight loss of
about 6% of baseline weight, with few adverse effects.
[50]

Lustig and colleagues reported the potential utility of octreotide in ameliorating the
disti
nct subclass of hypothalamic obesity.
[51]

The first glucagon
-
like peptide (GLP)
-
1 analog, exenatide, although not FDA
approved for obesity management, has been associated with modest weight loss

in
subjects with type 2 diabetes.

Peptide YY (3
-
36) is being developed as a nasal inhaler. Preliminary, ongoing
phase 1 and 2 trials yielded encouraging results.
[52, 53, 54]

Amylin is the synt
hetic version of pramlintide and does not have an FDA
indication for obesity management. However, this drug is clearly associated with
variable weight loss in people with type 1 or 2 diabetes, while improving overall
glycemic control.

Drugs no longer used

Some agents that initially showed promise were later demonstrated to be poor
prospects in rigorous randomized intervention trials. These include guar gum,
chitosan, axokine (or ciliary neurotrophic factor, the use of which was associated
with development
of autoantibodies and marked reduction in anorexiant potency in
about 30% of subjects), leptin (except in the rare subclass of leptin
-
deficient
obesity), St John's wort, psyllium, conjugated linoleic acid, chromium, and
ginseng, among others.

Comorbiditie
s

The management of obesity is not complete without attention being paid to various
potential comorbidities.

29


Addressing these issues can have profound effects on the patient's well
-
being and
risk of morbidity and mortality.

Public policy and obesity manage
ment

Although management of obesity in the individual subject is important, realizing
that obesity is a public
-
health problem is vital. Successful management of the
obesity pandemic requires public health professionals and administrators to make
tough poli
cy decisions.

The multibillion
-
dollar food industry and the link between this industry and the
consumer (including retailers and caterers) must be included in this public
-
health
effort. The high
-
density foods, snacks, and drinks that are so common in the
developed world and that now are infiltrating developing countries must be
recognized as major factors in this pandemic.

Large
-
scale public
-
health education aimed at all age groups must be implemented
with the same fervor and zeal that characterized past
advertisements for tobacco.
Such public
-
health initiatives must be accompanied by an equally spirited effort to
educate the public and to encourage regular participation in exercise and outdoor
recreational activities among individuals of all ages.

Fat su
bstitutes

One strategy to prevent obesity that is being explored in the dietary industry
involves use of fat substitutes.

Olestra (Olean) has been approved for use as a dietary supplement and additive in
various fast foods, such as potato chips and cracker
s. Olestra has a calorie value of
0 kcal/g, whereas fat has approximately 9.1 kcal/g. Olestra consists of a sucrose
polyester backbone with 6
-
8 fatty
-
acid side chains; this structure making it too
large for digestive enzymes of the gut to hydrolyze it. In
many trials, olestra had
fairly good tolerability, though it apparently is less tasty than materials cooked in
regular fat. The major adverse effects reported were flatulence, bloating, diarrhea,
and loose stools. Because of the concern for possible malabs
orption of fat
-
soluble
vitamins, the FDA requires all olestra
-
prepared foods to be supplemented with
these vitamins.

Sitostanol (Benecol) is a plant stanol ester preparation that is used as a spread
similar to margarine. It blocks cholesterol absorption i
n the intestine, with no
clinically significant alterations in triglyceride or HDL
-
C values.

30


Preliminary reports suggest the potential utility of agents that impede dietary
carbohydrate absorption. Tagatose is one of the agents in this class that is
under
going trials.





Surgic
al Care

Surgical therapy for obesity

(
bariatric surgery
) is the only available therapeutic
modality associated with clinically significant and sustained weight loss in subjects
with morbid obesity associated with comorbidities. Evidence shows that well
-
performed bariatric surgery in carefully selected patients

and a good
multidisciplinary support team substantially ameliorates the morbidities associated
with severe obesity. Although bariatric surgery is the only therapeutic method
associated with consistently demonstrable sustained weight loss, it is expensive,

highly procedure and surgeon specific, and certainly not the solution for the
burgeoning obesity epidemic.

Patient selection for these procedures must be addressed along the same stringent
lines as those discussed above for potential patients for medical

weight
-
management programs (see Medical Care).

The presence of comorbidities is not a contraindication to these surgical
procedures; however, the patient's condition must be stabilized and adequately
treated before surgery. At a minimum, consider these p
rocedures only in subjects
with a BMI greater than 40 kg/m
2

and/or a weight greater than 45 kg above the
age
-
defined and sex
-
defined ideal weight. For subjects with BMIs of 35
-
40 kg/m
2
,
several other comorbidities must be present to justify these procedure
s.

Among the comorbidities reported to be ameliorated and/or resolved by bariatric
surgery are type 2 diabetes mellitus, hypertension, heart failure, peripheral edema,
respiratory insufficiency, asthma, dyslipidemia, esophagitis, pseudotumor cerebri,
slee
p disorders, operative risk, osteoarthrosis, thromboembolism, and urinary
incontinence. Other reports suggest improved quality of life and fertility among
postsurgical patients. Although other outcomes are difficult to demonstrate and are
awaiting clear do
cumentation, these procedures may substantially reduce
macrovascular complications (eg, myocardial infarction); stroke; amputations;
obesity
-
related malignancies; and a predisposition to infection, hernias, and
varicose veins.

31


Although most bariatric proc
edures were initially developed in the setting of
laparotomies, they now are increasingly performed laparoscopically, with reduced
postoperative morbidity. The laparoscopic approach to bariatric surgery is
particularly well developed in Europe.

Among the
standard bariatric procedures are (1) horizontal gastroplasty, (2) roux
-
en
-
Y gastric bypass, (3) biliopancreatic bypass, (4) silicone gastric banding, (5)
adjustable gastric banding, (6) jejunoileal bypass procedures, and (7)
biliopancreatic bypass with du
odenal
-
switch procedures.

Although available data on the effectiveness of all these procedures are still
relatively scant, anecdotal reports of individual patients and a few reports of the
most commonly performed procedures (gastric restriction and gastric

bypass
procedures) lend veracity to the long
-
term effectiveness of bariatric surgery.

Ashley and colleagues (1993) examined 114 subjects who underwent vertical
-
band
gastroplasty.
[55]
About 60% l
ost more than 50% of their excess body weight over 1
year. No patient lost less than 25%, and, within a year of the surgery, mean BMI
had decreased from 44.8 to 32.5 kg/m
2
.

Flickinger and associates (1984) examined 210 subjects who received roux
-
en
-
y
gast
ric bypass.
[56]
The mean weight loss was 51 kg in 18 months, which was then
maintained over 36 months of follow
-
up. Only 4% required a repeat operation.

Sugerman and colleagues (1992) reported t
hat, among patients undergoing gastric
bypass, two thirds of their excess body weight was lost over 2 years, 60% of the
excess body weight lost was maintained, and more than 50% of excess body
weight lost was maintained at 9
-
years follow
-
up.
[57]

Roux
-
en
-
y and other gastric
-
bypass procedures generally result in more weight
loss than gastric
-
restriction procedures. When 329 subjects receiving vertical
gastroplasty procedures were compared with 623
subjects undergoing roux
-
en
-
Y
gastric bypass, weight loss was maintained in 47% and 62%, respectively, over 5
-
9
years of follow
-
up.
[57]

Other adjunctive procedures that may be performed but that

have an unclear utility
include visceral fat removal, omentectomy, subcutaneous fat panniculectomy, and
large
-
volume subcutaneous fat liposuction. Klein and colleagues (2004) indicated
that liposuction in itself has no utility in improving cardiac risk fa
ctor among
subjects with obesity.
[58]

Previous procedures, such as jaw wiring, insertions of gastric balloon, and
insertions of gastric wrap are no longer popular because of their poor results
32


c
ompared with those newer procedures and because of their high complication
rates.

Vagotomy has declined in popularity. On its own, vagotomy is associated with
some weight loss, but the weight is typically regained within a few years. A few
reports suggest

that, when vagotomy is performed with gastric bypass, it increases
weight loss by as much as 20%, but this finding has not been consistently
replicable.

Among the major procedure
-
specific postoperative complications to watch for are
wound dehiscence, sto
mal strictures, erosions or ulcers, postprocedure diarrhea,
malabsorption, dumping syndrome, and anastomotic leaks with a potential for
mediastinitis or peritonitis. In addition, gastric
-
specific operations can be
associated with persistent vomiting, metab
olic alkalosis, thiamine deficiency, and
malabsorption of iron and vitamin B
-
12. These operations are more commonly
associated with weight
-
loss failure and inadvertent splenectomy than other
methods.

Prevalences for adverse events are approximately 70% for

dumping, 50% for dairy
intolerance, 40% for constipation and headaches, 15% for depression, and 33% for
hair loss. Vitamin B
-
12 deficiency was found in 25% of patients; incisional
hernias, anemia, diarrhea, or abdominal pain, in 15% each; and arrhythmias
or
single or multiple vitamin deficiencies not involving vitamin B
-
12, in 10% each.

The mortality rate associated with standard bariatric surgical procedures in an
experienced center should not exceed 1.5
-
2%. The surgical mortality rate is less
than 0.5%
at centers specializing in bariatric surgery. Mortality rates exceeding this
rate suggest a risk
-
to
-
benefit ratio that probably is unacceptable.

Subjects who receive bypass procedures are particularly prone to micronutrient
deficiency states, especially o
f calcium, vitamin B
-
12, folate, and iron.

Among the major specific complications associated with malabsorptive operations
are uncontrolled diarrhea, steatorrhea, malabsorption of fat
-
soluble vitamins,
potassium and/or magnesium deficiency, blind
-
loop syn
drome (which includes
enteritis, arthropathy, and liver cirrhosis), gallstone development, urolithiasis, and
metabolic encephalopathy.

If failure is defined as an inability to ameliorate comorbidities or prevent
recurrence of such comorbidities, gastric b
ypass appears to have a failure rate of
approximately 20%. Failure rates based on weight loss are controversial. The
overall failure rates for malabsorptive procedures are relatively low, though the
33


need for reversal of the surgery because of resulting adv
erse effects appears to be
relatively high.

Despite the morbidity and mortality risk associated with bariatric surgery, the few
reports on the follow
-
up of subjects undergoing these procedures suggest overall
improvement in quality of life. Even more conv
incing than this finding is that most
subjects who undergo these procedures, irrespective of their postoperative
complications and difficulties, indicate that they would undergo the procedures
again if necessary.

Emerging data suggest that gastric pacing
achieved by using implantable
electrodes may have substantial significant weight
-
loss effects. This outcome was
initially discovered with the use of gastric pacemaker

devices for gastroparesis in
subjects with diabetes.

Transneuronix conducted the first s
et of trials of a device, and findings were
largely reported in abstracts. Medtronic, an established company in the arena of
medical devices that developed continuous, subcutaneous insulin
-
pump
technology, acquired Transneuronix, as seen in the image below
. Recruitment is
ongoing for the Appetite Suppression Induced by Stimulation Trial (ASSIST) to
evaluate this technology in patients with obesity and type 2 diabetes.

Gastric electrical
-
stimulation device
.


Cigaina (2002) reported that 10 patients in whom

the pacing device was
laparoscopically implanted showed a mean excess weight loss of about 25% at 3
-
year follow
-
up.
[59]

Similar findings were replicated in several European studies with a total

cohort of
about 50 patients.


34


Consultations



Psychiatrist: Consultation with a psychiatrist is vital for identifying persons
with psychiatric disorders and personality disorders such as depression,
mania, and obsessive disorders that may be worsened by attempts at weight
loss if not adequately treate
d and controlled.



Dietitians



Exercise and physical therapists



Behavioral scientists and/or psychologists



Bariatric surgeon, in appropriate setting

Diet

See Medical Care.

Activity

See Medical Care.



Medication Summary

Few medications are available for the management of obesity. The list

of putative
therapeutic agents being investigated has increased considerably with the explosion
in our knowledge of the pathogenesis of obesity. Improved understanding of the
neurocircuitry of the feeding
-
satiety cycle has provided many potential targets
for
designer therapeutic agents that are being developed (see image below).


35



Central nervous system neurocircuitry for satiety and feeding cycles.


Most medications available for managing obesity are approved only for short
-
term
use. Available literature indicates that their utility is severely limited when they are
given in this fashion. Obesity is a chronic medical condition. As with similar
chronic

conditions (eg, diabetes, hypertension), after therapeutic agents are
stopped, the relapse rate is high. The need for any pharmaceutical regimen to be
combined with a sustained exercise, dietary adjustment, and a behavioral
-
change
regimen to sustain weigh
t loss further complicates the successful management of
obesity.

The only FDA
-
approved medication for long
-
term management of obesity in
adults and adolescents is orlistat. Adolescents represent the next wave of the
obesity pandemic that is anticipated in

the next few decades.

A Japanese study found evidence that beverages containing high amounts of
catechin, a flavonoid found in green tea, may aid in preventing obesity.
[60]
Patients
in the inves
tigation, all of whom had type 2 diabetes mellitus, ingested either 582.8
mg or 96.3 mg of catechins per day, by drinking green tea. By the 12th week,
participants receiving the higher catechin dose had undergone a significantly
greater reduction in waist
circumference than did patients receiving the lower dose.

Anorexiants

Class Summary

Anorexiants are administered to manage obesity. Indications
included weight loss
and maintenance of weight loss, in conjunction with a reduced calorie diet,
specifically in patients who are obese with an initial BMI of 30 or 27 mg/m
2
and
other risk factors (eg, diabetes mellitus, dyslipidemia, hypertension).

Orlistat (Xenical)



GI lipase inhibitor that induces weight loss by inhibiting nutrient absorption.
Effectiveness in producing weight loss does not depend on systemic absorption.
M
ay reduce absorption of some fat
-
soluble vitamins (A, D, E, K) and beta
-
carotene. Administer multivitamin supplement containing fat
-
soluble vitamins PO
qd 2 h ac or 1 h pc.

36


Adrenergic Agonists

Class Summary

Stimulants release tissue stores of epinephrine, causing subsequent alpha
-

and/or
beta
-
adrenergic stimulation, have provided benefits to patients with obesity.
Approved in adults for short
-
term use (8
-
12 wk).

Caffeine



Natural xanthine derivative that directly stimulates all levels of CNS,
cardiovascular system, and voluntary muscles. Increases gastric acid secretion and
renal blood flow. Has mild diuretic activity.

Phentermine (Adipex
-
P)



Sympathomimetic amine that increases release and reuptake of norepinephrine and
dopamine. Anorexiant effect occurs as result of satiety
-
center stimulation in
hypothalamic and limbic areas of brain. Pharmacologic component of
comprehensive weight
-
reduction program (including behavioral modification,
caloric restriction, exercise) intended for patients with initial BMI 30 or 27 kg/m
2

and other risk factors (eg, d
iabetes, hyperlipidemia, hypertension).

Diethylpropion



Sympathomimetic amine effective as adjunct anoretic therapy of exogenous
obesity. Anorexiant effect occurs as a result of
satiety
-
center stimulation in
hypothalamic and limbic areas of brain. Controlled substance with high potential
for abuse and addiction.


Further Inpatient Care

Although weight
-
management programs may be based in an outpatient or inpatient
setting, no rigorous evidence suggests that inpatient programs are necessarily
superior to outpatient programs of similar structure and content.

37


Inpatient programs may offer the convenience of easy access to patients and ease
of monitoring, but they are ex
pensive to run, difficult to reimburse, and generally
considerably disrupt the patients' regular routine. In addition, they offer little
guarantee of sustained effect.

The major role for inpatient evaluations is in the immediate postoperative period
after

antiobesity surgery and in the management of major complications, such as
clinically significant respiratory or cardiac compromise.

Fu
rther Outpatient Care

As with the management of other chronic medical conditions that are not presently
curable (eg, diabetes mellitus, hypertension, bronchial asthma), long
-
term success
in the management of obesity is contingent on long
-
standing follow
-
up

with the
program.

Visits may not need to occur as frequently during follow
-
up as during the initial
weight
-
loss phase, but they are paramount if the lessons learned regarding diet,
exercise habits, and behavioral patterns are to be maintained.

Experience

from the lifestyle intervention group of subjects in the Diabetes
Prevention Program and the ongoing Diabetes Prevention Program Observation
study have borne out the importance of regular follow
-
up.

Deterrence/Prevention

Because of the sheer prevalence of obesity and the anticipated worsening of the
pandemic in the next few decades, prevention is by far the most desirable means
to
curb the consequences and economic load of obesity. However, few trials have
addressed this issue, and those performed thus far have had mixed results.

Results of some public health education initiatives in Singapore and parts of China
that are only no
w being evaluated suggest, as hoped, that such programs have the
potential for reducing the incidence and prevalence of obesity and the major
comorbidities of obesity, such as type 2 diabetes and hypertension.

Until recombinant DNA methods are developed e
nough to enable the alteration of
genes that predispose individuals to obesity, the only options available are to
develop a massive public health education program aimed at both adults and
children to change their eating, activity, and behavioral habits.

The potential for possible leptin sensitizers may assist in changing feeding habits.

38


Given the global proportions of obesity, a concerted approach is needed and should
involve cooperative efforts among public health authorities, caterers, the fast food
ind
ustry, and organizers of sports and outdoor games.

In 2010, the American Heart Association
-
American Stroke Association (AHA
-
ASA) issued guidelines for the primary prevention of stroke, with the following
recommendations:
[61]



Diet and nutrition: A diet that is low in sodium and high in potassium is
recommended to reduce blood pressure. Diets that promote the consumption
of fruits, vegetables, and low
-
fat dairy products such as the DASH
-
style diet
help lower blood pressure and may lower risk of stroke.



Physical inactivity: Increasing physical activity is associated with a
reduction in the risk of stroke. The goal is to engage in at least 30 minutes of
moderate intensity activity on a daily basis.



Obesity and body fat distribution: Weight reduction among overweight and
obese persons, is recommended to reduce blood pressure and risk of stroke.

Complications

The potential complications and associations of obesity are detailed in the image
below.


Comorbidities of obesity.


The so
-
called Pickwickian syndrome named after the boy who was obese in
Charles Dickens’
Pickwick
Papers

is a combined syndrome of obesity
-
related
hypoventilation (related to the severe mechanical respiratory limitations to chest
excursion from severe obesity) and sleep apnea (which may be from obstructive,
central, or both mechanisms).

39


Apart from the

metabolic complications associated with obesity, a paradigm of
increased intra
-
abdominal pressure has been recognized. This pressure effect is
most apparent in the setting of marked obesity (BMI ≤50) and is espoused by
bariatric surgeons, including Sugerm
an and colleagues (1992).
[57]

Given findings from bariatric surgery and animal models, this change in pressure
may play a (potentially major) role in the pathogenesis of comorbidities of obesity
,
such as pseudotumor cerebri, lower
-
limb stasis, ulcers, dermatitis,
thrombophlebitis, reflux esophagitis, abdominal hernias, and possibly hypertension
and nephrotic syndrome.

Some reports, including those by Adelman and colleagues and Kasiske and
Jennet
te, suggest an association between severe obesity and focal
glomerulosclerosis.
[62, 63, 64]
These complications, in particular, improve substantially
or resolve early after bariatric surgery, well before clinically significant weight loss
is achieved.

Prognosis

The association between obesity and morbidity is not in doubt.

However, the previous notion that the increased mortality and morbidity in patients
who are obese was not entirely due to comorbidities was controver
sial.

Results of several observational studies detailed by the Expert Panel on the
Identification, Evaluation, and Treatment of Overweight Adults and results from
other reports by Allison, Bray, and others exhaustively show that obesity, on its
own, is as
sociated with increased cardiovascular morbidity and mortality and
increased all
-
cause mortality.

For a person with a BMI of 25
-
28.9 kg/m
2
, the relative risk for coronary heart
disease is 1.72. This risk progressively increases with an increasing BMI.
Therefore, with BMIs greater than 33 kg/m
2
, the relative risk is 3.44.

Similar trends were demonstrated in the relationship between obesity and stroke or
congestive heart failure.

Overall, obesity is estimated to increase the cardiovascular mortality rate

4
-
fold
and the cancer
-
related mortality rate 2
-
fold.
[20]

As a group, people who are severely obese have a 6
-

to 12
-
fold increase in the all
-
cause mortality rate.

40


A longitudinal study by Stessma
n et al of more than 1000 individuals indicated that
a normal BMI, rather than obesity, is associated with a higher mortality rate in
elderly people. The investigators determined that a unit increase in BMI in female
members of the cohort could be linked t
o hazard ratios (HRs) of 0.94 at age 70
years, 0.95 at age 78 years, and 0.91 at age 85 years. In men, a unit increase in
BMI was associated with HRs of 0.99 at age 70 years, 0.94 at age 78 years, and
0.91 at age 85 years. According to a time
-
dependent ana
lysis of 450 cohort
members followed from age 70 to age 88 years, a unit increase in BMI produced
an HR of 0.93 in women and in men.
[65]

Similar results to those in the Stessman study were found

in a Japanese
investigation of 26,747 older persons (aged 65
-
79 years at baseline). Tamakoshi et
al found no elevation in all
-
cause mortality risk in overweight (measured as BMI
25.0
-
29.9 in this study) or obese (BMI ≥ 30.0) males; slightly elevated hazar
d
ratios were found in women in the obese group, but not in the overweight group, in
comparison with women in the mid


normal
-
range group. In contrast, an
association was found between a low BMI and an increased risk of all
-
cause
mortality, even among per
sons in the lower
-
normal BMI range.
[66]

Patient Education

In
studies among low
-
income families, both adults and adolescents noted caloric
information when reading labels.
[67]
However, it did not affect food selection by
adolescents or the parental food sel
ections for their children. It appears that the
caloric content and distribution did not impact decision
-
making.


http://emedicine.medscape.com/article/123702
-
overview