Section One - Continue
OBESITY AND COMORBID* CONDITIONS
Obesity contributes to numerous and varied comorbid conditions. Complications
can occur in many organ systems, ranging from cardiovascular to respiratory
to orthopedic and even ophthalmologic. Overweight and obesity are known
risk factors for heart disease, diabetes, hypertension, gallbladder disease,
osteoarthritis, sleep apnea and other breathing problems, and some cancers
(uterine, breast, colorectal, kidney, and gallbladder). In addition, obesity
is associated with pregnancy complications, high blood cholesterol, menstrual
irregularities, hirsutism (excessive hair growth), stress incontinence,
psychological disorders, and increased surgical risk. Social discrimination
against obese persons has a strong negative effect on their quality of
Insulin Resistance Syndrome (Syndrome X). Obesity is
one of a constellation of markers for coronary heart disease and type
2 diabetes collectively known as Syndrome X, metabolic syndrome, or insulin
resistance syndrome. Visceral, or abdominal, fat is believed by many (but
not all) researchers to be more strongly associated with Syndrome X than
subcutaneous fat (34). Abdominal adiposity is an active metabolic tissue
and releases fatty acids, which accumulate in the liver and peripheral
tissues, reducing the effect of insulin on liver and muscle cells. The
free fatty acids are utilized by the muscles at the expense of glucose,
causing elevated levels of glucose in the blood that in turn result in
increased insulin output by the pancreas (34). Those individuals unable
to produce the large amounts of insulin needed to manage the elevated
glucose levels in the blood go on to develop type 2 diabetes (35). However,
even those individuals who do not develop type 2 diabetes are at increased
risk for coronary heart disease; hyperinsulinemia (elevated levels of
insulin) is associated with the other manifestations of Syndrome X: hypertension,
increased total cholesterol levels with low HDL and high LDL, and increased
triglyceride levels, all cardiovascular disease risk factors.
Data from the Bogalusa (Louisiana) Heart Study (36), an ongoing community-based
study of CVD risk factors in early life begun in 1972, were examined to
ascertain if childhood adiposity was also associated with Syndrome X.
Researchers found that childhood BMI and insulin levels were significant
predictors of adult Syndrome X clustering (obesity, hyperinsulinemia,
high blood pressure, and adverse levels of total cholesterol and triglycerides).
BMI was the strongest predictor, independent of familial insulin levels,
reinforcing the need to control weight in childhood and adolescence. A
separate study by Vanhala et al. found that children who were obese at
age seven were four times more likely to have Syndrome X as adults (37).
Weight loss can dramatically improve insulin resistance in obese persons,
with a resultant decrease in insulin and triglyceride levels, according
to Gerald Reaven, the researcher who first described Syndrome X (35).
A modest (15-pound) weight loss has been shown to improve Syndrome X manifestations,
including hypertension and high cholesterol and triglyceride levels. Regular
physical activity will also reduce Syndrome X risk factors . However,
while physical activity and weight loss each independently reduce insulin
resistance, the benefits of physical activity are reversed when the exercise
is stopped while weight loss benefits remain as long as weight is not
Diabetes. Obesity is the single most reliable predictor
of type 2 diabetes. As noted above, excess weight, especially abdominal
weight, causes insulin resistance, in part from increased fatty acid levels
released by adipose tissue. Higher levels of blood fats inhibit glucose
utilization by the muscles, increase accumulation of fats in the liver,
and stimulate insulin secretion, causing hyperinsulinemia, which plays
a significant role in the development of type 2 diabetes.
The link between elevated BMI and an increased risk for type 2 diabetes
has been demonstrated in various populations, including those with both
traditionally low and high rates of diabetes. Type 2 diabetes was formerly
called adult-onset diabetes, a designation no longer applicable as it
is now being diagnosed with alarming frequency among young adults, adolescents,
and even younger children (38). A recent study by researchers at Yale
University of 167 obese children and adolescents found that 25% of the
children and 21% of the adolescents had impaired glucose tolerance, an
established risk factor of type 2 diabetes (38). Pediatric type 2 diabetes
has been found to occur most frequently among obese females aged 12 to
14 years (39). As the prevalence of obesity increases across all ages,
races, and ethnicities, so does the risk of diabetes and its complications.
According to researchers presenting to the Academy of Managed Care Pharmacy
in 1999, obesity is responsible for 61% of type 2 diabetes reported in
the United States. Wolf and Colditz found that obese individuals have
a 27.6-times excess risk of developing type 2 than do normal-weight persons
(40). Severely obese people, those with BMIs of 40+, are over 53 times
at risk for type 2 diabetes. Even minimal overweight poses a risk; the
Nurses’ Health Study reported that women with BMIs in the range
of 24-24.9 had a 5-fold greater risk of diabetes when compared with women
with BMIs of less than 22 (41). Data from the Professionals Health Study
demonstrated the same relationship between body weight and type 2 diabetes
among men. The risk of diabetes among men with a BMI of 35+ was 42 times
that of men with a BMI of less than 23 (42).
Among both men and women in the aforementioned studies, changing body
weight was a significant predictor of the risk for type 2 diabetes. Those
individuals who gained weight in adulthood were more likely than those
who maintained a stable weight to develop diabetes. Conversely, persons
who lost that extra weight lowered their risk.
In an article published in 2001 in Diabetes Care, Boyle, Honeycutt et
al. projected that the number of persons in the United Sates with diagnosed
diabetes will increase 165% between 2000 and 2052, from approximately
11 million persons to 29 million persons (43). Their estimates, which
utilize demographic, population growth, and prevalence rate projections,
are based on a linear increase; they point out, however, that prevalence
increased 16% between 1980 and 1984 and 33% between 1990 and 1998. If
the rate of increase continues to be nonlinear, their projections are
underestimates and the problem will be even more severe. In 2000, it was
reported that Eli Lilly & Co. was building the largest pharmaceutical
factory in the history of the industry to be dedicated to the production
of a single drug: insulin (11).
Hypertension. High blood pressure is one of the most
common complications of obesity, especially abdominal adiposity. Obesity-related
hypertension appears to be associated with the same hormonal substances
(cytokines) produced by adipose tissue that result in hyperinsulinemia
and the frequent development of type 2 diabetes. It has been suggested
that hyperinsulinemia increases sodium absorption; kidney abnormalities
affecting sodium and water reabsorption are significantly correlated with
obesity-related hypertension. Increased cardiac output, heart rate, and
increased circulating blood volume are also associated with obesity-related
hypertension. All of the mechanisms by which obesity influences blood
pressure are to date not totally understood; what is clear is that obesity-related
hypertension is a well-documented phenomenon that is multifactorial and
King and Wofford write that one-third of all hypertension cases are
related to obesity, while being obese raises the risk for developing hypertension
threefold (44). Data from the cohort of 5,209 men and women in the Framingham
Heart Study indicate that for every 10-pound weight gain, systolic blood
pressure rose by an average of 4.5 mm Hg (44). Conversely, a decrease
of 1 kg. (2.2 pounds) in body weight results in a decrease of 0.3 to 1
Even a modest weight loss (i.e., 5%-10% of body weight) can reduce blood
pressure, and this appears to be independent of sodium reduction (45).
The Nurses’ Health Study reinforced the findings that weight gain
in middle age is a risk factor for hypertension (46). According to that
study, women gaining only 2.1 to 4.9 kg in middle age had a 29% increase
in risk; women gaining 5.0 to 9.9 kg had a 74% increase in risk. A dramatic
fivefold increase was found among women who gained 25 kg or more after
the age of 18. A weight loss of 10 or more kg resulted in a 26% reduction
in risk. Researchers using data from the Bogalusa Heart Study of five
to 17-year-olds found that overweight children were 2.4 times as likely
to have elevated diastolic blood pressures and 4.5 times as likely to
have elevated systolic blood pressures as were their normal-weight counterparts
Hypercholesterolemia. Elevated cholesterol levels have
long been recognized as having an association with obesity. Obesity tends
to result in an elevation in total cholesterol and triglycerides and a
reduction in high-density cholesterol (HDL). Abdominal obesity can cause
an increased production of low-density cholesterol (LDL) particles that
are smaller and denser than normal, putting an individual at greater risk
of atherosclerosis, as well as increased very-low-density lipoprotein
(VLDL) and decreased HDL (48). It has been estimated that, on average,
each 10 pounds of excess fat produces an additional 10 mg. of cholesterol
daily, the equivalent of eating one extra egg yolk every day (49).
Data from the Third National Health and Nutrition Examination Survey
(NHANES III) indicate that the prevalence of elevated cholesterol levels
increased among younger men and women (less than 55 years of age) in all
overweight and obese classes compared with the reference group (BMI of
18.5-24.9), but levels did not increase significantly with increasing
weight class. Among older persons, elevated cholesterol levels were significantly
increased only among overweight subjects (BMI of 25-29.9) (50). Overweight
children in the Bogalusa Study were 2.4 times more likely to have total
cholesterol levels of greater than 200 mg/dl than normal-weight children
and adolescents (47).
Low-Grade Inflammation. Recent studies have indicated
that obesity is also associated with low-grade systemic inflammation.
Adipose tissue produces interleukin-6, a component of the immune system
that stimulates chronic inflammation, a condition that can increase an
individual’s risk for cardiovascular disease. This inflammation
can be measured through the concentration of C-reactive protein (CRP)
in the blood, with an increased risk of CVD directly associated with increasing
CRP levels. A 1999 study by Visser et al. examined NHANES III data collected
on over 16,000 adults from 1988-94 and found that both overweight and
obese men and women were more likely to have elevated CRP levels than
their lower-weight counterparts (51). A separate study by Visser et al.
of 3,512 children aged eight to 16 showed that overweight children were
also more likely to have elevated CRP than normal-weight children (52).
The overweight children also had higher white blood cell counts, a further
indication of low-grade inflammation.
Cardiovascular Disease. Obesity leads to an increase
in both heart attacks and strokes, independent of the effects associated
with diabetes, hypertension, and elevated cholesterol (49). As with diabetes
and hypertension, abdominal fat appears to be of special concern in the
development of cardiovascular disease. Both young and middle-aged men
and women have been found to be more likely to develop heart disease than
their leaner counterparts (53). Again using data from the Nurses’
Health Study, the risk for developing coronary heart disease (CHD) almost
doubled among women with a BMI between 25 and 29 and more than tripled
among those with a BMI of greater than 29 when compared with women whose
BMI was less than 21 (48). In a study of British men published in the
British Medical Journal in 1997, an increase of 1 kg/m in BMI above 22
was associated with a 10% increase in CHD incidence (48).
In addition to an increased risk of CHD, obesity has been associated
with myocardial hypertrophy, cardiomyopathy, and congestive heart failure
(48). Excess adipose tissue requires an increase in blood flow, the supply
of which requires greater cardiac output and increased cardiac workload.
As with hypertension, weight gain after the young adult years results
in additional risk independent of initial weight or other risk factors
associated with the gain (54).
Gallbladder Disease. The increased production of cholesterol
in obese persons also results in the increased incidence of gallstones
in both men and women. Approximately one in four obese individuals develops
gallstones, often necessitating surgery (49). Women of all ages and men
under the age of 55 exhibited the strongest association between increasing
obesity and increased incidence of gallbladder disease, according to NHANES
III data (53).
Liver Disease. Obesity is also a risk factor for liver
disease, in particular nonalcoholic steatohepatitis (NASH) or “fatty
liver.” The degree of fatty change in the liver is directly related
to the category of obesity and is thought to result from the accumulation
of triglycerides in the liver. According to one study, 80% of morbidly
obese (BMI>40) individuals were found to have fatty changes in the
liver (48). If not identified and treated, NASH can progress to cirrhosis.
It is estimated that approximately 12% of all cirrhosis cases are related
to obesity (55).
Cancer. The World Health Organization estimates that
between one-fourth and one-third of cancer cases in the world are attributable
to excess weight and physical inactivity (56). Even moderate weight gain
can put an individual at risk for certain cancers. “Gaining half
a pound a year or five pounds per decade” can be dangerous, according
to Dr. George Bray of Louisiana State University Medical Center (56).
The American Cancer Society has published data showing increased mortality
for colorectal and prostate cancer among obese men and for postmenopausal
breast, endometrial, cervical, ovarian, and gallbladder cancer among obese
women (48). Recent data have suggested a link between obesity and colon
cancer for both sexes (53). In fact, the Centers for Disease Control and
Prevention released data showing odds ratios for colon cancer of 1.79
for an individual with a BMI of 22-24 and 3.72 for one with a BMI of 28-30
when compared with both men and women with BMIs of less than 22 (48).
Obesity increases the risk of women developing hormone-related cancers.
Among postmenopausal women, women who gained more than 44 pounds (20 kg)
after the age of 18 were twice as likely as other women to get breast
cancer. As adipose tissue is the main source of estrogen for postmenopausal
women, this risk is limited to those women who do not use hormone replacement
therapy (48). Endometrial cancer is the most common gynecological cancer
among U.S. women, and obesity has been shown to increase the risk of developing
this cancer, especially in older women (53).
Female Reproductive System Disorders. Decreased fertility
has been noted among obese premenopausal women, along with pregnancy complications,
menstrual irregularity, and anovulatory cycles (48). Hirsutism (the presence
of excess body and facial hair) has been associated with obesity, as has
stress incontinence caused by weak pelvic-floor muscles (57).
Osteoarthritis. The Arthritis Foundation estimated
that approximately 16 million people in the United States had osteoarthritis,
the breakdown of cartilage in the joints, in 2000 (53). Osteoarthritis
is most commonly found in the hip, knee, and carpometacarpal joint of
the hand. A study of middle-aged women published in 1996 in the Journal
of Rheumatology estimated that for every 1 kg of weight gained, the risk
of osteoarthritis of the knee and hand increased by 9%-11% (48). A Finnish
study of 7,000 adults found that the odds ratio for osteoarthritis was
2.8 among persons with a BMI of 35 compared with those with a BMI of 25
(48). Conversely, the Framingham study reported that a decrease in BMI
of 2 or more, even over a 10-year period, reduced the risk of developing
osteoarthritis in the knee by more than 50% (48).
Asthma. A 1999 study of NHANES II data examined the
link between childhood obesity and increased asthma incidence and found
that the heaviest children were 77% more likely to have asthma symptoms
(58). Researchers have suggested that the increased weight on the lungs
compromises the airways, causing asthma symptoms; in addition, excess
weight could lead to inflammation in the respiratory tract.
Obstructive Sleep Apnea. It has been estimated that
as many as 60% to 70% of persons suffering from obstructive sleep apnea
(OSA), a condition characterized by short repetitive episodes of impaired
breathing during sleep, are obese (59). Obesity, especially in the upper
body, increases the risk for OSA by narrowing the individual’s upper
airway. OSA can result in systemic hypertension, myocardial ischemia,
cardiac arrhythmia, and stroke.
Pseudotumor Cerebri. Pseudotumor cerebri, or idiopathic
intracranial hypertension, refers to a condition of elevated cerebrospinal
fluid pressure without having a mass in the brain. Pseudotumor cerebri
is characterized by headache, neck and back pain, double vision, and episodes
of vision loss due to swollen optic nerves. Unless treated, the condition
can lead to blindness. While the cause for the condition is as yet unknown,
it occurs most frequently among overweight and obese females of childbearing
age. Approximately 90% of affected persons are obese, with women two to
eight times more at risk than men (60).
Psychological Disorders. There are numerous theories
concerning the link between obesity and depression. Many causes have been
proposed, including social stigma, negative self-image, dieting issues,
the poor health that often accompanies obesity, and a neurochemical connection
between the two conditions.
Obesity has been associated with compulsive eating and binge eating
disorders, each of which is independently linked to major depression.
These disorders are forms of food addiction, a behavior typified by a
loss of control over the amount of food consumed, whether on a consistent
basis or in the form of binging. It has been estimated that over 30% of
persons seeking medical treatment for obesity are binge eaters, as are
50% of persons seen in nonmedical weight-reduction programs (61). Binge
eaters often crave and subsequently overeat carbohydrates, avoiding foods
that are protein-rich; perhaps two-thirds of all obese persons are carbohydrate
Social Disorders. In general, the obese have poorer
prospects than their leaner counterparts in many endeavors. Landlords
are less likely to rent to obese individuals (63). In the workplace, there
is increased absenteeism among obese persons (63). Several studies have
found that heavier women earn less than normal-weight women (64). This
association, however, held true only among obese versus nonobese white
women; little difference in income was found among African-American women.
In their examination of discrimination against the obese in the workplace,
Roe and Eichwort reported that 16% of employers interviewed would not
employ obese persons and 44% would only employ such persons under special
Two studies found that, even with comparable scholastic achievements,
obese students were not accepted at prestigious colleges as often as normal-weight
students (63). A study of 1,500 white, black, and Hispanic children followed
from age 10 until age 14 reported that significantly lower self-esteem
was observed by age 14 among obese children of all races. These children
were also found to be more likely to engage in risky behaviors such as
alcohol and tobacco use (65). Early adolescence was determined to be a
critical time for overweight and obese children, for it is during these
years that they are developing their sense of self-worth.
* Comorbid conditions refer to other conditions or diseases that can
accompany or result from obesity. Return to Top