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5/14/2016 Obesity in adults: Health hazards

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Official reprint from UpToDatewww.uptodate.com ©2016 UpToDate

Author George A Bray, MD

Section Editor F Xavier Pi-Sunyer, MD, MPH

Deputy Editor Kathryn A Martin, MD

Obesity in adults: Health hazards

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Apr 2016. | This topic last updated: Jan 02, 2016.

INTRODUCTION — The mor bidity and mortality associated with being overweight or obese have been known

to the medical profession for more than 2000 years [1]. Overweight refers to a weight above the “normal” range.

This is determined by calculating the body mass index (BMI, defined as the weight in kilograms divided by

height in meters squared). Overweight is defined as a BMI of 25 to 29.9 kg/m , obesity as a BMI of >30 kg/m .

Severe obesity is defined as a BMI >40 kg/m (or ≥35 kg/m in the presence of comorbidities).

The health hazards associated with obesity are reviewed here. The prevalence of and therapy for obesity, and

the evaluation of the overweight patient are discussed elsewhere. (See "Obesity in adults: Overview of

management" and "Obesity in adults: Prevalence, screening, and evaluation".)

MORTALITY

Effect of BMI on mortality — In general, greater body mass index (BMI) is associated with increased rate of

death from all causes and from cardiovascular disease (CVD) (figure 1). This is particularly true for those with

severe obesity [2]. Obesity is typically defined on the basis of the BMI, which is measured using a patient's

weight (in kg) divided by height (in m ).

A number of large epidemiologic studies have evaluated the relationship between obesity and mortality [2-13].

As an example, a meta-analysis of 97 studies (2.88 million individuals) showed that, compared with normal

weight, being obese was associated with higher all-cause mortality (hazard ratio [HR] 1.18, 95% CI 1.12-1.25

for all grades of obesity combined) [14]. Estimates for the annual number of excess deaths attributable to

obesity in the United States are variable and range from 111,909 to 365,000 [15,16].

Being overweight also appears to be associated with decreased survival in some [ 5,10,17], but not all

[12,14,18], studies. As examples:

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A prospective study from the United States evaluated the relationship between BMI and risk of death

over a maximum follow-up period of 10 years among over 500,000 men and women aged 50 to 71 years

[5]. Among the subset of individuals 50 years of age (when prevalence of chronic disease is low) who had

never smoked, an increased risk of death was associated with being either overweight (20 to 50 percent

increase in those between 26.5 to 29.9 kg/m ) or obese (two- to over threefold increase in those ≥30

kg/m ). The risk of all-cause mortality with increasing BMI of 25 kg/m or higher appears to be

independent of gender and ethnicity [5,19].

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In the Prospective Studies Collaboration analysis of 57 pr ospective studies (894,000 European and North

American adults followed for a mean of eight years), mortality was lowest among men and women with a

BMI between 22.5 to 25 kg/m , and there was a 30 percent increase in overall mortality for each 5 kg/m

increase in BMI (figure 1) [10].

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In a pooled analysis of 19 prospective studies (1.4 million Caucasian adults with median follow-up of 10

years) from the National Cancer Institute Cohort Consortium (NCICC), that was restricted to participants

who never smoked and did not have diagnosed cancer or heart disease, a BMI of 20 to 24.9 kg/m was

associated with the lowest all-cause mortality, and there was a similar 30 percent increase in mortality

per 5 unit increase in BMI in the 25 to 49.9 kg/m range [17].

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In a pooled analysis of 19 prospective cohort studies (1.1 million Asian adults with mean follow-up of nine

years) from the Asia Cohort Consortium, the lowest risk of death was among persons with a BMI in the

range of 22.6 to 27.5 kg/m2 [20].

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There are a number of factors that may help explain the variability in the overweight-related mortality estimates.

Variable choice of statistical techniques and study populations affect estimates of mortality risk [ 21]. In

addition, BMI is affected by diet and exercise habits, which may affect health (and mortality) in ways that may

be mediated by BMI or independent of it.

Normal weight central obesity — Both overall obesity, defined by BMI, and abdominal obesity or central

obesity (assessed by measuring waist circumference, waist-to-hip ratio [WHR], or waist/height ratio), are

associated with an excess risk of CVD (see 'Heart disease' below). The WHR is infrequently used by

clinicians and is not currently recommended as part of the routine obesity evaluation by the American Heart

Association/American College of Cardiology/Obesity Society guideline, although it was in the previous version.

Data from the Third National Health and Nutrition Examination Survey (NHANES III) suggest that normal-

weight central obesity (normal BMI with increased WHR) is associated with higher mortality than BMI-defined

mortality, particularly when compared to individuals without central obesity [22]. In a cross-sectional survey of

over 15,000 individuals, men with a normal BMI (18.5 to 24.9 kg/m ) but central obesity (WHR ≥0.90) had the

highest total mortality risk when compared to men without central obesity who were normal weight, overweight

(25 to 29.9 kg/m ), or obese (≥30 kg/m ) (HR 1.87, 2.24, and 2.42, respectively). Normal weight women with

central obesity (WHR ≥0.85) also had higher mortality risk compared to normal weight and obese women

without central obesity (HR 1.48 and 1.32, respectively). A limitation of the study is that central obesity was

determined by WHR only; no quantitative imaging studies of adipose tissue were performed. These data

suggest that normal weight individuals with central obesity appear to have an increased mortality risk and

should be targeted for lifestyle modification strategies.

Metabolically healthy obese patients — The term “metabolically healthy” obese and overweight refers to

individuals who do not have adiposity-associated cardiometabolic abnormalities (hypertension,

hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, impaired fasting glucose and/or evidenceof insulin resistance, abnormal C-reactive protein) [23]. Although obese people are at increased risk for adverse

long-term outcomes even in the absence of metabolic abnormalities, it is less certain whether this applies to

metabolically healthy overweight individuals. In a pooled analysis of four studies with 10-year follow-up,

metabolically healthy obese individuals had a significantly increased risk of mortality compared with

metabolically healthy normal weight individuals [13] However, in metabolically healthy overweight individuals,

the increased risk of mortality did not reach statistical significance, even when the analysis was restricted to

studies with at least 10 years of follow-up (relative risk [RR] 1.21, 95% CI 0.91-1.61). Thus, some of the

variability in mortality estimates among overweight people may be due to inadequate adjustment in the

analyses for these metabolic factors or a follow-up which is too short to demonstrate a significantly increased

mortality risk in overweight metabolically healthy individuals.

Low BMI — A separate question is related to outcomes in individuals with lower BMI values. The following

observations illustrate the range of findings from variably-defined patient populations:

In a meta-analysis of 97 studies (2.88 million individuals), compared with normal weight, being overweight

was associated with a lower all-cause mortality (HR 0.94, 95% CI 0.91-0.96) [14]. These results were

similar after adjustment for smoking status, preexisting disease, and weight and height reporting method

(measured or self reported).

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In the Prospective Studies Collaboration, subjects with BMI below 22.5 kg/m had higher mortality

compared with subjects with a BMI of 22.5 to 25 kg/m [10]. The excess mortality was predominantly

due to smoking-related diseases (respiratory and cancer).

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In the analysis of studies from the NCICC, mortality risk was significantly higher among participants with

BMI below 22.5 kg/m (HR 2.02, 95% CI 1.94-2.11 for women with a BMI of 15 to 18.4 compared with

22.5 to 24.9 kg/m ) [17]. However, the increased mortality rate among those with a BMI below 22.5 kg/m

was lower in those who were healthy and never smoked compared with all participants (HR 1.47 versus2.02 and 1.37 versus 1.98 for women and men, respectively, with BMI 15 to 18.4 versus 22.5 to 24.9 kg/m

). In addition, the association between underweight and increased mortality among healthy subjects who

never smoked was weaker after 15 years of follow-up than after five years of follow-up (HRs 1.21 and

1.73, respectively).

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These findings, taken together, suggest that the association between a low BMI and increased mortality is

probably, in part, an artifact of preexisting disease and/or smoking.

Cause-specific mortality — The association between BMI and cause-specific mortality was illustrated in the

Prospective Studies Collaboration analysis [10]. In the upper BMI range (25 to 50 kg/m ), each 5 kg/m

increase in BMI was associated with a significant increase in mortality from each of the following disorders:

Similar findings were noted for cardiovascular mortality (overall cardiovascular disease, coronary heart disease

[CHD], ischemic stroke, and hemorrhagic stroke) in the Asian Cohort Consortium. Compared with a BMI of

22.5 to 24.9 kg/m , East Asians with a higher BMI showed a “dose-effect” with a significantly-increased risk of

total cardiovascular death (HRs 1.09, 1.27, 1.59, 1.74, and 1.97 for BMI ranges 25 to 27.4, 27.5 to 29.9, 30 to

32.4, 32.5 to 34.9, and 35 to 50, respectively) [24]. East Asians with a BMI below 17.5 kg/m also had an

increased risk of cardiovascular mortality (HRs 2.16 and 1.19 for BMI less than 15 and 15.0 to 17.4,

respectively). The association between BMI and cardiovascular disease mortality was weaker in South Asians(HR 1.27, 95 percent CI 0.81-1.97 for South Asians with a BMI of 35 to 50 compared with 22.5 to 24.9 kg/m ).

Overweight during adolescence — Being overweight during adolescence may also increase the risk of

premature death as an adult. This was illustrated in an analysis of the Nurses' Health Study where the risk of

premature death increased with higher BMIs at age 18 years. Compared with a BMI of 18.5 to 21.9 kg/m at

age 18 years, the risk of premature death significantly increased with a BMI greater than 25 kg/m (HRs 1.66

and 2.79 for a BMI of 25 to 29.9 and ≥30 kg/m , respectively) [25]. This association could only partly be

explained by being overweight as an adult.

Trends in cardiovascular risk factors — The NHANES study reported that although the prevalence of

obesity (BMI >30 kg/m ) increased dramatically in the United States between 1960 and 2000 (15 to 30percent), the impact of obesity on mortality decreased over time, thought to be related to more aggressive and

effective management of cardiovascular risk factors [16,26]. As expected, there was an increase in diagnosed

diabetes (1.8 to 5.0 percent) between 1960 and 2000 that was most prominent in obese subjects (2.9 to 10.1

percent) [26]. In contrast, the prevalence of other major cardiovascular risk factors declined substantially

between 1960 and 2000:

These changes occurred in all weight groups, including obese individuals, and were associated with increases

in the use of lipid-lowering drugs and antihypertensive medications. As a result, the impact of obesity on

mortality appeared to decrease over time [16]. However, the NHANES study also reported that these

cardiovascular improvements have not been accompanied by reduced disability in the obese older population

In the Asian Cohort Consortium, both East Asian and Indian and Bangladeshi populations with BMI below

20.1 kg/m had significantly higher mortality compared with subjects with BMI of 22.6 to 25 kg/m (HRs

1.84 and 1.59, respectively, for BMI 15.1 to 17.5 kg/m ) [ 20]. When the analysis was limited to

nonsmokers, the elevated risk was attenuated but remained significant (HRs 1.72 and 1.54).

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A report from the NHANES defined underweight as a BMI


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[27]. In fact, obese participants were more likely than the non-obese to report functional impairments over time.

In contrast to the NHANES data, in an analysis based upon a much larger cohort followed for over 20 years,

there was no evidence that the magnitude of the association between obesity and mortality had decreased over

time [28].

Effect of fitness — Fitness level is also an important factor in obese individuals, as shown in a meta-analysis

of 10 studies. Compared to normal weight-fit individuals, unfit individuals had twice the risk of mortality

regardless of BMI [29]. Overweight and obese-fit individuals had similar mortality risks as normal weight-fit

individuals. In contrast, in the Lipids Research Clinics and the Nurses' Health Studies, both physical fitness

and adiposity were independent predictors of mortality, and higher levels of physical activity did not negate the

association between obesity and mortality [30,31].

Life expectancy — Obesity in adulthood is also associated with a striking reduction in life expectancy for both

men and women. Among 3457 subjects in the Framingham Study, those who were obese (BMI ≥30 kg/m ) at

age 40 years lived six to seven years fewer than those who were not (BMI ≤24.9 kg/m ). Those who were

overweight (BMI 25 to 29.9 km/m ) at age 40 years lived about three years fewer, and those who were both

obese and smoked lived 13 to 14 years fewer than normal-weight nonsmokers [32].

A second study noted a similar reduction in life expectancy, particularly among younger adults. The impact of

obesity on years of life lost (YLL) was greater for men than women and for whites than blacks [ 33].Furthermore, in a model designed to estimate the joint effects of obesity and smoking cessation on longevity

and quality of life using data from NHANES I, II, III, and 2004 through 2006, the negative impact of obesity on

life expectancy is forecasted to outweigh the health benefits of smoking cessation [34].

It has been suggested that the steady rise in life expectancy during the past two centuries may come to an end

because of the increasing prevalence of obesity [35].

MORBIDITY — Obesity and increased central fat are associated with increased morbidity in addition to

mortality [36,37]. In a survey of adults in the United States, overweight and obese individuals had a higher

relative risk of hypertension, hypercholesterolemia, and diabetes mellitus compared with normal weight

individuals [38]. The risk of hypertension and diabetes increased with increasing body mass index (BMI)(adjusted odds ratios 2.6 to 4.8 [for hypertension] and 1.6 to 5.1 [for diabetes] in individuals with BMIs ranging

from 25 to ≥40 kg/m ).

In the Nurses' Health and the Health Professionals Studies, the risk of developing a chronic disease

(gallstones, hypertension, heart disease, colon cancer, and stroke [in men only]) increased with increasing

BMI, even in those in the upper half of the healthy weight range (BMI 22.0 to 24.9 kg/m ) (figure 2) [39,40].

While these data suggest that a BMI


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(NHANES III), where individuals with high waist circumference values (men >102 cm [40 inches], women >88

cm [35 inches]) were more likely to have diabetes, hypertension, and dyslipidemia compared with those who

had normal waist circumference values [44].

Weight gain after age 18 years in women and after age 20 years in men also increases the risk of type 2

diabetes. The Nurses' Health Study, for example, compared women with stable weight (those who gained or

lost


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with hypertension is discussed in greater detail elsewhere. (See "Obesity and weight reduction in

hypertension", section on 'Effects of weight reduction'.)

Dyslipidemia — Obesity is associated with several deleterious changes in lipid metabolism although, as noted

above, the prevalence of obesity-associated dyslipidemia may be decreasing. Unfavorable obesity-related

effects include high serum concentrations of cholesterol, low-density-lipoprotein (LDL) cholesterol, very-low-

density-lipoprotein (VLDL) cholesterol, and triglycerides, and a reduction in serum high-density-lipoprotein

(HDL) cholesterol of about 5 percent [52]. The last effect may be most important since a low serum HDL

cholesterol concentration carries a greater relative risk of coronary heart disease (CHD) thanhypertriglyceridemia.

Central fat distribution also plays an important role in the serum lipid abnormalities. (See "Obesity in adults:

Prevalence, screening, and evaluation".)

Gout — The risk of developing gouty arthritis increases with body weight and with the amount of weight gain

during adulthood. The influence of BMI on hyperuricemia and gout is discussed in more detail elsewhere. (See

"Asymptomatic hyperuricemia".)

Heart disease — Obesity is associated with a number of risk factors for cardiovascular disease, including

hypertension, insulin resistance and diabetes mellitus, dyslipidemia, high plasma fibrinogen concentrations and

other prothrombotic factors [53], and in women with central obesity, an increase in thromboxane-dependentplatelet activation [54].

Obesity is also associated with increased risks of coronary disease, heart failure, and as described above,

cardiovascular and all-cause mortality. Weight loss (if achieved through lifestyle interventions, medication, or

surgery) is associated with an improvement in cardiovascular risk factors [ 55]. However, liposuction of large

amounts of abdominal fat does not appear to improve cardiovascular risk profiles. (See "Obesity, weight

reduction, and cardiovascular disease" and "Bariatric operations for management of obesity: Indications and

preoperative preparation" and "Obesity in adults: Overview of management", section on 'Liposuction'.)

Coronary disease — Obesity has been associated with an increased risk of CHD and cardiovascular

mortality in many observational studies, including the Framingham Heart Study and the Nurses' Health Study(figure 2) [40,49,52]. In an analysis of pooled data from 97 prospective cohort studies (1.8 million individuals),

compared with normal weight (BMI ≥20 to


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Heart failure — There is an important association between obesity and heart failure. In an analysis from

the Framingham Heart Study in which almost 6000 individuals without a history of heart failure (mean age 55

years) were followed for a mean of 14 years [ 63], heart failure developed in 496 (8.4 percent). The risk of heart

failure was increased approximately twofold in obese (BMI ≥30 kg/m ) compared with non-obese subjects.

After adjusting for established risk factors (eg, hypertension, coronary disease, diabetes, left ventricular

hypertrophy), the risk of heart failure increased 5 percent in men and 7 percent in women for each increment of

1 kg/m in BMI. Approximately 11 percent of cases of heart failure in men and 14 percent in women could be

attributed to obesity alone. The risk was also increased in overweight (BMI 25 to 29.9 kg/m ) women but not

men. (See "Epidemiology and causes of heart failure".)

There are a number of mechanisms by which obesity could predispose to heart failure:

Overweight and obesity may also be associated with subclinical right ventricular dysfunction, independent of

obstructive sleep apnea, diabetes, mellitus, and hypertension [66].

Myocardial steatosis — One potential mechanism for heart disease in obesity is thought to be excessivelipid accumulation in the myocardium. In rodent models, myocardial steatosis appears to cause left ventricular

hypertrophy and nonischemic dilated cardiomyopathy. Studies in healthy subjects or patients with heart failure

(using magnetic resonance spectroscopy) suggest that myocardial triglyceride content increases with

increasing BMI [67]. The increasing adiposity of the heart may contribute directly to the structural (left

ventricular hypertrophy) and functional (hyperdynamic circulation) cardiac adaptations seen with obesity.

ECG in morbid obesity — Morbid obesity can cause changes in cardiac morphology that can alter the

surface electrocardiogram (ECG). One study compared the ECGs of 100 obese subjects and 100 normal

subjects; none of the subjects had any evidence of cardiac disease [68]. Compared with the normal subjects,

the obese subjects had the following alterations on the ECG:

Prolonged QT interval (which improves with weight loss) has also been reported in obese individuals [69,70].

Atrial fibrillation/flutter — Obese individuals (BMI >30 kg/m ) are significantly more likely to develop atrial

fibrillation (AF) than those with a normal BMI (


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The association with BMI appears to be stronger for sustained atrial fibrillation when compared with transient or

intermittent atrial fibrillation [73].

Stroke — Obesity is associated with an increased risk of stroke. An analysis by the Emerging Risk Factors

Collaboration of 21 studies (over 85,000 participants) found that the risk of ischemic stroke significantly

increased for every one standard deviation increase in BMI, waist circumference, and waist-to-hip ratio (HR

1.20, 1.25, and 1.25, respectively) [57]. After adjustment for age, gender, smoking status, blood pressure,

history of diabetes, and total and HDL cholesterol, the risk was markedly attenuated (HR 1.06 to 1.14).

Similar findings were reported in the Global Burden of Metabolic Risk Factors for Chronic Diseases

Collaboration, an analysis of pooled data from 97 prospective cohort studies (1.8 million individuals) [56]. Both

overweight and obesity were associated with an increased risk of stroke (HR for each 5 kg/m higher BMI

1.18, 95% CI 1.14-1.22). Approximately 75 percent of the excess risk for stroke was mediated by blood

pressure, serum cholesterol, and blood glucose. Blood pressure was the most important mediator, accounting

for 65 percent of the excess risk.

Data from the Nurses' Health Study and Women’s Health Study found that both an increased BMI (≥27 kg/m )

and weight gain after age 18 years were associated with an increased risk of ischemic stroke [75]. Neither BMI

nor weight gain was associated with an increase in the risk of hemorrhagic stroke, although the relationship

persisted for total stroke risk. In men, increasing BMI was associated with an increased risk of both ischemic

and hemorrhagic stroke in one report [76] and with total and ischemic (but not hemorrhagic) in another [ 77].

Venous thrombosis — Obesity has been associated with an increased risk of deep vein thrombosis and

pulmonary embolus. This topic is reviewed in detail elsewhere. (See "Overview of the causes of venous

thrombosis", section on 'Obesity'.)

Dementia — Obesity may be associated with an increased risk of later dementia. (See "Risk factors for

cognitive decline and dementia", section on 'Lifestyle and activity'.)

Hepatobiliary disease — Obesity affects the hepatobiliary system, primarily by causing cholelithiasis. This

has been demonstrated in many studies. In the Nurses' Health Study, women with a BMI 1 to 1.5 kg/week). (See "Epidemiology of and risk factors for

gallstones".)

The quantity of fat in the liver may also be increased in obese subjects. Steatosis is a common abnormality

seen on liver biopsy; it is due to the deposition of triglycerides in hepatocytes in the form of lipid droplets. In

obese subjects, excess triglycerides may be produced due to increased peripheral lipolysis. Triglycerides are

normally packaged into VLDL; if, however, the rate of triglyceride synthesis exceeds the rate of clearance, the

excess accumulates in the liver. Steatosis resolves with weight loss, except after intestinal bypass. (See

"Pathogenesis of nonalcoholic fatty liver disease".)

GERD/GI cancer — Obesity is a risk factor for gastroesophageal reflux disease (GERD), erosive esophagitis,

esophageal adenocarcinoma, and gastric cancer. (See "Epidemiology, pathobiology, and clinical manifestations

of esophageal cancer", section on 'Obesity' and "Risk factors for gastric cancer", section on 'Obesity'.)

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Osteoarthritis — The incidence of osteoarthritis is increased in obese subjects and accounts for a major

component of the cost of obesity. Osteoarthritis commonly develops in the knees and ankles; this may be

directly related to the trauma associated with excess body weight. However, it also occurs more frequently in

non-weight-bearing joints, suggesting that there are components of the obesity syndrome that alter cartilage

and bone metabolism independent of weight-bearing [79].

In one study of over 1000 women, obesity was classified as the upper tertile of BMI; the boundaries of the

middle tertile were 23.4 and 26.4 kg/m . The age-adjusted odds ratios of unilateral and bilateral osteoarthritis at

the knee, determined from x-rays of the knees, comparing the high and low tertiles of BMI were 6.2 and 18,respectively [80]. Comparing the middle and low tertiles of BMI, the odds ratios for osteoarthritis at various

joints were as follows:

A twin study found similar results: each kilogram increase in body weight (compared with a twin control) was

associated with an increased risk of radiographic features of osteoarthritis at the knee and carpometacarpal

joint [81].

Conversely, weight loss is associated with a decreased risk of osteoarthritis. In a study of 800 women, a

decrease in BMI of 2 kg/m or more in the preceding 10 years decreased the odds for developing osteoarthritis

by over 50 percent [82]. This benefit was also found among those women with a high risk for osteoarthritis due

to a high baseline BMI (≥25 kg/m ). (See "Risk factors for and possible causes of osteoarthritis".)

Infection — Obesity is associated with an increased susceptibility to infections, including postoperative,

nosocomial, and skin and soft tissue infections [83-86]. In addition, obese patients are more likely than normal

weight individuals to have respiratory complications during influenza season [87,88]. Although the effect of

obesity on the immune system is not clearly defined, it appears to have an effect independent of coexisting

risk factors (eg, diabetes) [87]. A suggested explanation is that obese individuals are more likely to have lowlevels of leptin, which may play a role in the immune response, and high levels of pro-inflammatory cytokines

[83]. (See "Physiology of leptin", section on 'Immune Function' and "Epidemiology of pandemic H1N1 influenza

('swine influenza')", section on 'Obesity' and "Treatment of seasonal influenza in adults", section on 'Definition

of high risk'.)

Skin changes — Several changes in the skin are associated with obesity.

Respiratory system — Sleep apnea is the most important respiratory problem associated with obesity and

diabetes [90], with several studies confirming that obesity is a major risk factor for the development of

obstructive sleep apnea. (See "Clinical presentation and diagnosis of obstructive sleep apnea in adults" and

"Obstructive sleep apnea and cardiovascular disease".)

Other alterations in pulmonary function may occur, including higher residual lung volume associated with

increased abdominal pressure on the diaphragm, decreased lung compliance and increased chest wall

impedance, ventilation-perfusion abnormalities, reduced strength and endurance of respiratory muscles,

depressed ventilatory drive [91], and bronchospasm (asthma). (See "Pathogenesis of obesity hypoventilation

2

Knee – 2.9●

Carpometacarpal joint – 1.7●

Distal interphalangeal joint – 1.5●

Proximal interphalangeal joint – 1.2●

2

2

Stretch marks (striae) are common and reflect the tension on the skin from expanding subcutaneous

deposits of fat.

●

Acanthosis nigricans, with deepening pigmentation around the neck, axilla (picture 1), knuckles, and

extensor surfaces, may occur in connection with obesity. While this skin condition has been associatedwith cancer in some patients (eg, gastric cancer), it is not related to an increased risk of cancer in obese

subjects. The proposed cause of this lesion is sustained hyperinsulinemia [89]. (See "Insulin resistance:

Definition and clinical spectrum".)

●

Hirsutism in women may result from increased production of testosterone, which is often associated with

visceral obesity. (See "Pathogenesis and causes of hirsutism".)

●

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http://www.uptodate.com/contents/obesity-i n-adults-health-hazards?topicKey=ENDO%2F5370&elapsedTimeMs=5&source=search_result&searchTerm… 10/26

syndrome".)

Obesity has been thought to be a risk factor for asthma [ 92,93], but in one cohort study, obesity was

associated with dyspnea but not asthma [94] (see "Risk factors for asthma", section on 'Obesity'). These

effects on respiratory function are considered to be relatively benign or uncommon, compared with the

problems induced by obesity-associated hypoventilation or obstructive sleep apnea.

Cancer — Certain forms of cancer occur with increased frequency in obese men and women [ 95-97]. Obesity

also increases the likelihood of dying from cancer. In a meta-analysis of 141 studies that included 282,137

cancer cases, a 5 kg/m increase in BMI in men was associated with esophageal, thyroid, colon, and renal

cancers (RR 1.52, 1.33, 1.24, and 1.24, respectively) [98]. In women, a 5 kg/m increase was associated with

endometrial, gallbladder, esophageal, and renal cancers (RR 1.59, 1.59, 1.51, and 1.34, respectively).

Associations were similar in studies from North America, Europe, Australia, and the Asia-Pacific region, with

the exception of stronger associations between BMI and breast cancer in the Asia-Pacific populations.

In a subsequent cohort study with prospectively collected data from the United Kingdom Clinical Practice

Research Datalink, 5.24 million adults without a previous cancer diagnosis were followed to investigate the

association between BMI and 22 of the most common cancers [99]. During the observation period (7.5 years),

166,955 individuals developed one of the cancers. For some cancers, there was a linear association and for

others, a nonlinear association with substantial variation due to individual characteristics (gender, age,

menopausal status, smoking). High BMI was associated with an increased risk of the following cancers:

Overweight and obesity were estimated to account for between 2 (thyroid) and 41 (endometrial) percent of

these cancers.

The relationship between obesity and risk of breast, endometrial, colon, and prostate cancer are reviewed

separately. (See "Factors that modify breast cancer risk in women" and "Endometrial carcinoma: Epidemiology

and risk factors", section on 'Obesity' and "Risk factors for prostate cancer", section on 'Obesity' and

"Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Obesity' .)

Endocrine changes — In addition to the changes noted above (diabetes and hyperlipidemia), several other endocrine changes are associated with obesity. Irregular menses and anovulatory cycles are common in obese

women, and fertility may be decreased. There are also reports of an increased risk of pregnancy-induced

hypertension, and cesarean delivery may be more frequent. (See "The impact of obesity on female fertility and

pregnancy".)

Disorders of sexual arousal and orgasm may be more common in overweight and obese women [ 100]. (See

"Sexual dysfunction in women: Epidemiology, risk factors, and evaluation".)

In men, obesity is an independent risk factor for erectile dysfunction. (See "Overview of male sexual

dysfunction".)

Kidney disease — Obesity is associated with multiple other conditions that are known to cause compromised

renal function, including hypertension, diabetes, and the metabolic syndrome. However, data from the

Framingham Offspring study, the Hypertension Detection and Follow-Up Program, and the Multiphasic Health

Testing Services Program suggest that obesity may be independently associated with the risk of developing

2

2

Endometrial●

Gallbladder ●

Kidney●

Liver ●

Colon●

Cervical●

Thyroid●

Ovarian●

Postmenopausal breast●

Leukemia●

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chronic kidney disease [101-104]. Focal segmental glomerulosclerosis and obesity-related glomerulopathy

(glomerular enlargement and mesangial expansion), both of which are associated with proteinuria, have been

described in patients with severe obesity. Obesity-related glomerulopathy may be reversible with weight loss.

(See "Epidemiology of chronic kidney disease" and "Secondary factors and progression of chronic kidney

disease" and "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis".)

Kidney stones — Obesity and weight gain during adulthood appear to be associated with an increased risk

of kidney stones [105]. (See "Risk factors for calcium stones in adults".)

Urinary incontinence — In women, overweight and obesity are important risk factors for urinary incontinence.

(See "Evaluation of women with urinary incontinence", section on 'Risk factors' .)

Psychosocial function — Obese subjects are often exposed to public disapproval because of their fatness.

This stigma is seen in education, employment, and health care, among other areas. In a study of over 10,000

adolescents, women who were overweight (defined as a BMI above the 95 percentile for age and sex)

completed fewer years of school (0.3 year less), were less likely to be married (20 percent less likely), had

lower household incomes ($6710 less per year), and had higher rates of household poverty (10 percent higher)

than the women who had not been overweight, independent of their baseline socioeconomic status and

aptitude test scores [106]. Men who had been overweight were less likely to be married (11 percent less likely).

Depression has also been seen in association with severe obesity, particularly in younger patients and inwomen [107].

COST OF OBESITY — In the Swedish Obesity Study, obese subjects had 1.4 to 2.4 times the number of

days of sick leave than did normal-weight subjects and were 1.5 to 2.8 times as likely to draw a disability

pension. In addition, yearly drug costs were significantly higher in obese compared with normal-weight people

[108]. Surgical treatment for obesity lowered diabetes and cardiovascular disease-related drug costs but

increased gastrointestinal drug costs, resulting in similar total drug costs for surgically and conventionally-

treated obese patients. (See "Bariatric operations for management of obesity: Indications and preoperative

preparation".)

Other reports have found an increase in health care expenditures among overweight subjects [ 37,109-112]. Inone study, subjects at the extremes of body mass index (BMI) had the highest expenditures, while those in the

middle of the BMI range (26 to 27 kg/m ) had the lowest probability of using health care dollars. In a second

review of over 17,000 people in a health maintenance organization, there was an association between BMI and

annual rates of outpatient visits and inpatient days, annual cost of outpatient visits, costs of outpatient

pharmacy and laboratory services, and total cost of care (both inpatient and outpatient) [ 110].

Specifically, mean annual total costs were 25 percent greater among subjects with a BMI 30 to 34.9 kg/m

relative to a BMI of 20 to 24.9 kg/m and 44 percent greater among those with a BMI of 35 kg/m or higher.

The higher costs were predominantly explained by the presence of coronary heart disease (CHD),

hypertension, and diabetes. Similar data have been presented in the Netherlands and France.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics”

and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6

grade reading level, and they answer the four or five key questions a patient might have about a given

condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read

materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed.

These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth

information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these

topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on

“patient info” and the keyword(s) of interest.)

th

2

2

2 2

th th

th th

Basics topics (see "Patient information: Weight loss treatments (The Basics)" and "Patient information:

Health risks of obesity (The Basics)")

●

Beyond the Basics topics (see "Patient information: Weight loss treatments (Beyond the Basics)" and●

http://www.uptodate.com/contents/weight-loss-treatments-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/health-risks-of-obesity-the-basics?source=see_linkhttp://www.uptodate.com/contents/weight-loss-treatments-the-basics?source=see_linkhttp://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/110http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/37,109-112http://www.uptodate.com/contents/bariatric-operations-for-management-of-obesity-indications-and-preoperative-preparation?source=see_linkhttp://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/108http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/107http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/106http://www.uptodate.com/contents/evaluation-of-women-with-urinary-incontinence?source=see_link&sectionName=Risk+factors&anchor=H21988183#H21988183http://www.uptodate.com/contents/risk-factors-for-calcium-stones-in-adults?source=see_linkhttp://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/105http://www.uptodate.com/contents/epidemiology-classification-and-pathogenesis-of-focal-segmental-glomerulosclerosis?source=see_linkhttp://www.uptodate.com/contents/secondary-factors-and-progression-of-chronic-kidney-disease?source=see_linkhttp://www.uptodate.com/contents/epidemiology-of-chronic-kidney-disease?source=see_linkhttp://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/101-104


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SUMMARY

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"Patient information: Weight loss surgery and procedures (Beyond the Basics)")

Obesity is associated with significant excess morbidity and mortality. Estimates for annual obesity-

associated mortality are extremely variable. (See 'Mortality' above.)

●

Obesity and increased central fat are associated with increased morbidity, including diabetes mellitus,

hypertension, heart disease, stroke, sleep apnea, and many others. Weight loss will improve most of

these morbidities. (See 'Morbidity' above.)

●

The management of obesity is discussed in detail elsewhere. (See "Obesity in adults: Overview of

management".)

●

http://www.uptodate.com/contents/obesity-in-adults-overview-of-management?source=see_linkhttp://www.uptodate.com/contents/weight-loss-surgery-and-procedures-beyond-the-basics?source=see_linkhttp://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/18http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/17http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/16http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/15http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/14http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/13http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/12http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/11http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/10http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/9http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/8http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/7http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/6http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/5http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/4http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/3http://www.uptodate.com/contents/obesity-in-adults-health-hazards/abstract/2http://www.uptodate.com/contents/license


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Topic 5370 Version 27.0

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GRAPHICS

All-cause mortality versus BMI for each sex in the range 15 to 50

kg/m (excluding the first five years of follow-up)

Relative risks at age 35 to 89 years, adjusted for age at risk, smoking, and study, were

multiplied by a common factor (ie, floated) to make the weighted average match the PSC

mortality rate at ages 35 to 79 years. Floated mortality rates shown above each square

and numbers of deaths below. Area of square is inversely proportional to the variance of

the log risk. Boundaries of BMI groups are indicated by tick marks. 95% CIs for floated

rates reflect uncertainty in the log risk for each single rate. Dotted vertical line indicates

25 kg/m (boundary between upper and lower BMI ranges in this report). Above 25

kg/m , mortality was on average approximately 30 percent higher for every 5 kg/m

higher BMI.

2

2

2 2


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BMI: body mass index; PSC: Prospective Studies Collaboration.

Reproduced with permission from: Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and

cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet

2009; 373:1083. Illustration used with the permission of Elsevier Inc. All rights reserved.

Graphic 73156 Version 4.0


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Body mass index and the risk of disease

Increasing body mass index (BMI kg/m ), even within the normal

range of BMI (21 to 24.9), is associated with an increased risk of type

2 diabetes, hypertension, coronary heart disease, and cholelithiasis.Panel A shows data for women in the Nurses' Health Study, initially 30

to 55 years of age, who were followed for up to 18 years. Panel B

shows data for men in the Health Professionals Follow-up Study,

initially 40 to 65 years of age, who were followed for up to 10 years.

Data from: Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N

Engl J Med 1999; 341:427.


2


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Importance of body weight and exercise on development of

type 2 diabetes

Adjusted incidence of type 2 diabetes mellitus in 5990 men in relation to BMI (inkg/m ) and the level of physical activity (in kcal/week). The risk of type 2

diabetes was directly related to BMI, while regular exercise was protective except

for in men with a BMI below 24.

BMI: body mass index.

Data from: Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr. Physical activity and

reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;

325:147.


2


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Adult weight change and the risk of disease

Even a modest increase in weight as an adult is associated with an

increased risk of type 2 diabetes, hypertension, coronary heart

disease, and cholelithiasis. Panel A shows data for women in the

Nurses' Health Study, initially 30 to 55 years of age, who were

followed for up to 18 years. Panel B shows data for men in the Health

Professionals Follow-up Study, initially 40 to 65 years of age, who

were followed for up to 10 years.

Data from: Willett WC, Dietz WH, Colditz GA. Guidelines for healthy weight. N

Engl J Med 1999; 341:427.



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Obesity decreases insulin sensitivity in susceptible

subjects

Responsiveness to insulin (as assessed from the intravenous glucose

tolerance test) according to body weight in nondiabetic subjects with

no family history of type 2 diabetes mellitus in first-degree relatives

and in those with two parents with type 2 diabetes. Both groups had

similar insulin responsiveness at near normal ideal body weight, but

the degree of insulin resistance (decrease in insulin sensitivity) as

body weight increased was more pronounced in the offspring of

parents with type 2 diabetes.

Data from: Kahn CR. Banting Lecture. Insulin action, diabetogenes, and the

cause of type II diabetes. Diabetes 1994; 43:1066.



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