INTRODUCTION — The mortality and morbidity associated with overweight or obesity have been known to the medical profession for more than 2000 years [1]. Overweight refers to a weight above the "normal" range. Although imperfect, calculation of the body mass index (BMI, defined as the weight in kilograms divided by height in meters squared) is widely accepted for the determination of underweight, normal weight, overweight, and obesity. Overweight is defined as a BMI of 25 to 29.9 kg/m2, obesity as a BMI of >30 kg/m2. Severe obesity is defined as a BMI >40 kg/m2 (or ≥35 kg/m2 in the presence of comorbidities).
Adult obesity is associated with a striking reduction in life expectancy. It has been suggested that the steady rise in life expectancy seen during the past two centuries may end because of the increasing prevalence of obesity [2]. Individuals with obesity who smoke have a substantially greater reduction in life expectancy compared with those who smoke who do not have obesity or nonsmokers with obesity [3].
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) (calculator 1) is associated with increased rate of death from all causes and from cardiovascular disease (CVD) (figure 1). The risk profile can be expressed as a J-shaped curve with progressively greater mortality as BMI increases >25 kg/m2. This is particularly true for those with severe obesity [4]. Excess body weight contributed to four million deaths globally in 2015 and more than 320,000 deaths in the United States in 2014 [5].
Obesity — A number of large epidemiologic studies have evaluated the relationship between obesity and mortality [4,6-16]. In a meta-analysis of 230 cohort studies including over 30 million individuals, both obesity and overweight were associated with an increased risk of all-cause mortality [17]. The nadir of risk was observed at BMI 20 to 22 kg/m2 in studies of healthy never-smokers with the longest duration of follow-up (≥20 years).
Overweight — Being overweight also appears to be associated with increased mortality in some [8,13,18,19], but not all [15,20,21], studies. Evidence for excess mortality with increasing BMI includes the following:
●In an analysis of 57 prospective studies (894,000 European and North American adults followed for a mean of eight years), mortality was lowest among those with a BMI between 22.5 to 25 kg/m2, with a 30 percent increase in overall mortality for each 5 kg/m2 increase in BMI (figure 1) [13]. Similar results were seen in a second study [18]. The figure (figure 1) shows that increasing BMI for individuals of European ancestry has a curvilinear relation to mortality. The shape of the relationship may be different for different ethnicities, but the association remains [22-24].
●Other evidence that overweight and obesity are associated with excess mortality comes from a meta-analysis of 239 prospective studies of BMI and mortality in 10,625,411 participants in Asia, Australia and New Zealand, Europe, and North America [25]. For the four populations combined, all-cause mortality risk increased with increasing BMI (kg/m2) category: hazard ratio (HR) 1.07 for BMI 25.0 to <27.5, 1.20 for BMI 27.5 to <30.0, 1.45 for BMI 30.0 to <35.0, and 1.94 for BMI 35.0 to <40.0.
While increasing weight is still generally associated with increasing mortality, the BMI range associated with the lowest mortality has been increasing. Among three Danish cohorts, the BMI associated with the lowest all-cause mortality increased from 23.7 kg/m2 in a 1976 to 1978 cohort to 27.0 kg/m2 in a 2003 to 2013 cohort [26].
Controversies: Association BMI and mortality
"Metabolically healthy" patients with obesity — The term "metabolically healthy" patients with obesity and overweight refers to individuals who do not have clear adiposity-associated cardiometabolic abnormalities (ie, hypertension, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, impaired fasting glucose and/or evidence of insulin resistance, diabetes mellitus, abnormal C-reactive protein or abnormal liver function tests suggesting fatty liver disease) [27].
Despite the lack of metabolic abnormalities in a subset of patients with obesity, there is evidence of increased mortality. In a pooled analysis of four studies with 10-year follow-up, "metabolically healthy" individuals with obesity had a significantly increased risk of mortality compared with metabolically healthy normal-weight individuals [16]. 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. Thus, some of the variability in mortality estimates among overweight people may be due to risks that are proportional to excess fat mass; overweight individuals represent a spectrum of risk that is generally lower than individuals with obesity, at least over the short term.
It is evident that obesity varies in its impact on metabolic health and may often require many years to render measurable deleterious effects. In addition, an absence of quantitative impact on current metabolic health does not ensure a lack of impact on mental, social, or overall physical health.
The issue of "metabolically healthy" obesity is discussed in detail elsewhere. (See "Obesity: Association with cardiovascular disease", section on 'Metabolically "healthy" obesity'.)
Obesity paradox — Some studies have concluded that elevated BMI may improve survival in individuals with CVD, primarily congestive heart failure, a phenomenon called the "obesity paradox" [28,29]. However, these studies have not considered body fat distribution. Abdominal (versus gluteal) fat mass is strongly predictive of metabolic disease and mortality when measured by dual-energy x-ray absorptiometry (DXA) [30], waist-to-hip ratio [31], or waist circumference [30]. Thus, people with BMI <25 kg/m2 but with central obesity appear to have an increased mortality risk and should be targeted for lifestyle modification strategies.
In contrast to the many studies reporting that overweight is associated with higher mortality, there are data that suggest lower mortality for those with BMI in the 25 to 30 kg/m2 range [20]. Nevertheless, this was challenged by a large Australian study of 246,314 individuals, again showing the lowest mortality in those with a BMI of 22.5 to 24.99 kg/m2, not BMI 25 to 29.99 kg/m2 [32]. The obesity paradox is also reviewed elsewhere. (See "Obesity: Association with cardiovascular disease", section on 'Obesity paradox'.)
Mortality at low BMI ranges — A separate question is related to outcomes in individuals with low BMI values. The following observations illustrate the range of findings from variably defined patient populations:
●In the Prospective Studies Collaboration, subjects with BMI below 22.5 kg/m2 had higher mortality compared with subjects with a BMI of 22.5 to 25 kg/m2 [13]. The excess mortality was predominantly due to smoking-related diseases (respiratory and cancer).
●In the analysis of studies from the National Cancer Institute (NCI) Cohort Consortium, mortality risk was higher among participants with BMI below 22.5 kg/m2 (HR 2.02, 95% CI 1.94-2.11 for females with a BMI of 15 to 18.4 kg/m2 compared with 22.5 to 24.9 kg/m2) [18]. However, the increased mortality rate among those with a BMI below 22.5 kg/m2 was lower in those who were healthy and never smoked compared with all participants (HR 1.47 versus 2.02 and 1.37 versus 1.98for males and females, respectively, with BMI 15 to 18.4 kg/m2 versus 22.5 to 24.9 kg/m2). 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).
●In the Asian Cohort Consortium, subjects with BMI <20.1 kg/m2 had higher mortality than subjects with BMI of 22.6 to 25 kg/m2 (HR approximately 1.17) [24]. When the analysis was limited to nonsmokers, the elevated risk was attenuated.
●A report from the National Health and Nutrition Examination Survey (NHANES) defined underweight as a BMI <18.5 kg/m2, excluding subjects with illness-related weight loss [33], which is also the criterion used by the World Health Organization (WHO). Being underweight was associated with excess mortality (33,746 excess deaths) in both smokers and nonsmokers [33]. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'BMI-based classifications'.)
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 [13]. In the upper BMI range (25 to 50 kg/m2), each 5 kg/m2 increase in BMI was associated with a significant increase in mortality from coronary heart disease (CHD), stroke, diabetes mellitus, chronic kidney disease, and cancer (liver, kidney, breast, endometrial, prostate, and colon). For those with BMI between 30 and 35 kg/m2, median survival was reduced by two to four years; for 40 to 45 kg/m2, it was reduced by 8 to 10 years (similar to the effects of smoking). Years of life lost are highest for people who develop obesity at a younger age and live with obesity longer [34].
Similar findings were noted for cardiovascular mortality (overall CVD, CHD, ischemic stroke, and hemorrhagic stroke) in the Asian Cohort Consortium. Compared with a BMI of 22.5 to 24.9 kg/m2, study participants from China, Taiwan, Singapore, Japan, and Korea 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 kg/m2, respectively) [35].
Overweight during adolescence — Being overweight during adolescence may also increase the risk of premature death as an adult (figure 2). (See "Overview of the health consequences of obesity in children and adolescents", section on 'Adult cardiovascular disease'.)
Trends in cardiovascular risk factors — The NHANES study reported that, although the prevalence of obesity (BMI >30 kg/m2) increased dramatically in the United States between 1960 and 2000 (15 to 30 percent), the impact of obesity on mortality appeared to decrease over time, but this is thought to be related to more aggressive and effective management of cardiovascular risk factors [33,36]. As expected, there was an increase in diagnosed diabetes (1.8 to 5.0 percent) between 1960 and 2000 that was most prominent in subjects with obesity (2.9 to 10.1 percent) [36]. By contrast, the prevalence of other major cardiovascular risk factors declined substantially between 1960 and 2000:
●Serum total cholesterol ≥240 mg/dL (6.2 mmol/L) – Prevalence decreased from 34 to 17 percent
●Hypertension (which was defined as blood pressure ≥140/≥90 mmHg) – 31 to 15 percent
●Smoking – 39 to 26 percent
These changes occurred in all weight groups, including individuals with obesity, 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 [33]. However, the NHANES study also reported that these cardiovascular improvements have not been accompanied by reduced disability in the older population with obesity [37]. In fact, participants with obesity were more likely than those without obesity 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 [38].
Effect of fitness — Fitness level is also an important factor in individuals with obesity, as shown in a meta-analysis of 10 studies. Compared with normal-weight-fit individuals, unfit individuals had twice the risk of mortality regardless of BMI [39]. Fit individuals with overweight and obesity had similar mortality risks as fit individuals of normal weight. By 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 [40,41]. (See "Obesity in adults: Role of physical activity and exercise", section on 'Health benefits associated with exercise'.)
MORBIDITY — Obesity and increased central adiposity are associated with increased morbidity in addition to increased mortality [42,43]. In fact, obesity has surpassed smoking as the number one cause of preventable disease and disability. Over 230 comorbidities and complications of obesity have been identified, and weight loss will improve most of these [44]. As an example, in a survey of adults in the United States, individuals with overweight and obesity had a higher risk of hypertension, hypercholesterolemia, and diabetes mellitus compared with normal weight individuals [45]. In addition, 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 body mass index (BMI), even in those in the upper half of the healthy weight range (BMI 22.0 to 24.9 kg/m2) (figure 3) [46,47]. While these data suggest that a BMI <22.0 kg/m2 would be ideal, this is difficult to achieve for many individuals. In addition, the majority of subjects studied were White persons, and therefore these data cannot be directly extrapolated to other ethnic groups.
Metabolic risks
Diabetes mellitus
●Type 2 diabetes mellitus is strongly associated with obesity in all ethnic groups. More than 80 percent of cases of type 2 diabetes can be attributed to obesity, which may also account for many diabetes-related deaths. Weight gain after age 18 years in females and after age 20 years in males also increases the risk of type 2 diabetes (figure 4). (See "Pathogenesis of type 2 diabetes mellitus" and "Type 2 diabetes mellitus: Prevalence and risk factors".)
●Weight loss is associated with a decreased risk of type 2 diabetes [48]. (See "Prevention of type 2 diabetes mellitus", section on 'Lifestyle intervention' and "Nutritional considerations in type 2 diabetes mellitus".)
●The risk of type 2 diabetes may also be associated with specific dietary patterns. (See "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Dietary patterns'.)
●Insulin resistance with hyperinsulinemia is characteristic of obesity and is present before the onset of hyperglycemia. (See "Pathogenesis of type 2 diabetes mellitus".)
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, triglycerides, and a reduction in serum high-density lipoprotein (HDL) cholesterol of approximately 5 percent [49]. The last effect may be most important since a low serum HDL cholesterol concentration carries a greater relative risk of coronary heart disease (CHD) than hypertriglyceridemia. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia", section on 'Prevalence of lipid abnormalities'.)
Central adiposity also plays an important role in the serum lipid abnormalities. (See "Obesity in adults: Prevalence, screening, and evaluation".)
Cardiovascular
Hypertension — Blood pressure is often increased in those with obesity. The risk of hypertension is greatest in subjects with upper body and abdominal obesity. Weight loss in individuals with obesity is associated with a decline in blood pressure. The effect of weight loss in patients with obesity and hypertension is discussed in greater detail elsewhere. (See "Overweight, obesity, and weight reduction in hypertension", section on 'Weight reduction to lower blood pressure' and "Overweight, obesity, and weight reduction in hypertension", section on 'Hyperinsulinemia and insulin resistance'.)
Heart disease — Obesity is also associated with increased risks of coronary heart disease (CHD), heart failure, and, as described above, cardiovascular and all-cause mortality [50]. Weight loss (if achieved through lifestyle interventions, medication, or surgery) is associated with an improvement in cardiovascular risk factors [51]. (See "Obesity: Association with cardiovascular disease" and "Bariatric surgery for management of obesity: Indications and preoperative preparation".)
●Coronary heart disease – Obesity has long been associated with an increased risk for CHD. The risk of CHD in those with overweight and obesity is compounded by the frequent coexistence of other CHD risk factors, such as hypertension, dyslipidemia, and diabetes. How much of the risk is due to obesity alone has been uncertain. The relationship between obesity and CHD is reviewed elsewhere. (See "Obesity: Association with cardiovascular disease", section on 'Obesity and CHD'.)
●Heart failure – There is an important association between obesity and heart failure. There are a number of mechanisms by which obesity could predispose to heart failure (figure 5). The association between obesity and heart failure is discussed in detail elsewhere. (See "Obesity: Association with cardiovascular disease", section on 'Heart failure'.)
●Myocardial steatosis – One potential mechanism for heart disease in obesity is thought to be excessive lipid accumulation in the myocardium [52,53].
●Electrocardiogram findings – Severe obesity can cause changes in cardiac morphology that can alter the surface electrocardiogram (ECG). (See "Obesity: Association with cardiovascular disease", section on 'Mechanism of risk'.)
●Atrial fibrillation – Individuals with obesity (BMI >30 kg/m2) are significantly more likely to develop atrial fibrillation (AF) than those with a normal BMI (<25 kg/m2). (See "Epidemiology of and risk factors for atrial fibrillation", section on 'Obesity' and "Obesity: Association with cardiovascular disease", section on 'Atrial fibrillation'.)
Stroke — Obesity is associated with an increased risk of stroke, and stroke risk is mitigated by weight loss. (See "Overview of primary prevention of cardiovascular disease", section on 'Weight loss'.)
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'.)
Cancer — Excess weight is associated with an increased risk of multiple cancer types. Overweight and obesity were estimated to cause 40 percent of all cancers in the United States in 2014 [54].
In addition, obesity and overweight may increase the likelihood of dying from cancer. The mechanisms contributing to higher cancer incidence and mortality may include alterations in sex hormone metabolism, insulin and insulin-like growth factor levels, and adipokine pathways [55,56].
The rates of cancer related to excess weight are higher in females than males [54]. Although the strength of the association and the types of cancers vary somewhat across studies, multiple meta-analyses found strong evidence supporting the association between obesity and the following cancers [57,58]:
●Endometrial (see "Endometrial carcinoma: Epidemiology, risk factors, and prevention", section on 'Obesity')
●Kidney (see "Epidemiology, pathology, and pathogenesis of renal cell carcinoma", section on 'Obesity')
●Gastric cardia (see "Risk factors for gastric cancer", section on 'Obesity')
●Colon (see "Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Obesity')
●Rectum (see "Colorectal cancer: Epidemiology, risk factors, and protective factors", section on 'Obesity')
●Biliary tract (see "Epidemiology, pathogenesis, and classification of cholangiocarcinoma", section on 'Obesity')
●Pancreas (see "Epidemiology and nonfamilial risk factors for exocrine pancreatic cancer", section on 'Obesity and physical inactivity')
●Breast (in females who had never taken hormones) (see "Factors that modify breast cancer risk in women", section on 'Weight and body fat in postmenopausal women')
●Esophageal adenocarcinoma (see "Epidemiology and pathobiology of esophageal cancer", section on 'Obesity and metabolic syndrome')
●Ovarian (see "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors", section on 'Obesity')
●Multiple myeloma (see "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Epidemiology')
●Hepatocellular carcinoma (see "Epidemiology and risk factors for hepatocellular carcinoma", section on 'Obesity')
●Meningioma (see "Epidemiology, pathology, clinical features, and diagnosis of meningioma", section on 'Others')
Musculoskeletal
Osteoarthritis — The incidence of osteoarthritis is increased in subjects with obesity and accounts for a major component of the cost of obesity. Conversely, weight loss is associated with a decreased risk of osteoarthritis.
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 "Lifestyle modification and other strategies to reduce the risk of gout flares and progression of gout", section on 'Obesity and diet'.)
Gastrointestinal
Hepatobiliary disease — Obesity is associated with an increased risk of gallbladder disease and nonalcoholic fatty liver disease. In a meta-analysis of 17 studies with 55,670 individuals, the risk of gallbladder disease increased even within the normal BMI range [59]. Obesity affects the hepatobiliary system, primarily by causing cholelithiasis (figure 3). (See "Pathogenesis of nonalcoholic fatty liver disease".)
GERD/gastrointestinal cancer — Obesity is a risk factor for gastrointestinal-related disease, including gastroesophageal reflux disease (GERD), erosive esophagitis, esophageal adenocarcinoma, and gastric cancer. (See "Epidemiology and pathobiology of esophageal cancer", section on 'Obesity and metabolic syndrome' and "Risk factors for gastric cancer", section on 'Obesity'.)
Reproductive effects — Irregular menses and anovulatory cycles are common in females with obesity, and fertility may be decreased. Pregnant people with obesity are at increased risk for a number of maternal and perinatal complications, and the risks are amplified with increasing degrees of maternal obesity [60]. (See "Obesity in pregnancy: Complications and maternal management".)
Disorders of sexual arousal and orgasm may be more common in females with overweight and obesity. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation".)
In males, obesity is an independent risk factor for erectile dysfunction. (See "Epidemiology and etiologies of male sexual dysfunction".)
Genitourinary
Chronic kidney disease — Obesity is associated with multiple other conditions that are known to cause compromised kidney function, including hypertension, diabetes, and the metabolic syndrome. Data from 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 chronic kidney disease [61-63]. However, in the Framingham Offspring study, obesity was not an independent risk factor after adjustment for diabetes, systolic blood pressure, current smoking status, and HDL cholesterol level [64].
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 "Focal segmental glomerulosclerosis: Epidemiology, classification, clinical features, and diagnosis".)
Kidney stones — Obesity and weight gain during adulthood appear to be associated with an increased risk of kidney stones [65,66]. (See "Kidney stones in adults: Epidemiology and risk factors".)
Urinary incontinence — In females, overweight and obesity are important risk factors for urinary incontinence. (See "Evaluation of females with urinary incontinence", section on 'Risk factors'.)
Psychosocial function
Stigma of obesity — Those with obesity are often exposed to public disapproval because of their weight. This stigma is seen in education, employment, and health care, among other areas.
In the Coronary Artery Risk Development in Young Adults (CARDIA) study, weight discrimination in those who completed the 25-year follow-up examination was highest for White females (30.2 percent), lowest for White males (12 percent), and intermediate for Black males and females [67]. People with obesity are also discriminated against in hiring and more so for more physically demanding occupations [68,69].
Depression — Depression has also been seen in association with severe obesity, particularly in younger patients and in females [70].
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'.)
Respiratory system — Sleep apnea is the most important respiratory problem associated with obesity and diabetes, 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 in adults".)
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, and bronchospasm (asthma). (See "Epidemiology and pathogenesis of obesity hypoventilation syndrome".)
Experimental models, prospective cohort studies, population-based case-control studies, and a meta-analysis suggest that patients with an elevated BMI are at increased risk for developing asthma. This risk may be greater for nonallergic asthma than allergic asthma. (See "Risk factors for asthma", section on 'Obesity'.)
Lastly, as noted above, 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'.)
Infection — Obesity is associated with an increased susceptibility to infections, including postoperative, nosocomial, respiratory, and skin and soft tissue infections [71-74].
Influenza — Individuals with obesity are more likely than normal-weight individuals to have respiratory complications during influenza season and are more likely to be hospitalized with influenza [75-77]. (See "Seasonal influenza in adults: Treatment", section on 'Definition of high risk'.)
COVID-19 — Observational data link obesity with increased morbidity and mortality from coronavirus disease 2019 (COVID-19) [78-82].
Representative studies include:
●In a study including two cohorts (approximately 2500) patients hospitalized with COVID-19 in New York City, obesity was associated with an increased risk of intubation or death among adults less than 65 years of age [82].
●In a study including almost 7000 adults with COVID-19, there was a J-shaped association between BMI and risk of death at 21 days [83]. Patients with BMIs of 40 to 44 kg/m2 and >45 kg/m2 had an increased risk of death compared with patients with a BMI of 18.5 to 24 kg/m2 (RR 2.68, 95% CI 1.43-5.04 and 4.18, 95% CI 2.12-8.26) respectively.
●In a pooled analysis of 75 studies, individuals with obesity had a 46 percent higher risk for being COVID-19 positive, a 113 percent higher risk of being hospitalized, a 74 percent higher risk for intensive care unit (ICU) admission, and a 48 percent increased mortality [84].
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) [75,77]. (See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on 'Assess risk for severe disease' and "COVID-19: Clinical features", section on 'Risk factors for severe illness'.)
Skin changes — Several changes in the skin are associated with obesity.
●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. The proposed cause of this lesion is sustained hyperinsulinemia [85]. (See "Insulin resistance: Definition and clinical spectrum".)
●Hirsutism in females may result from increased production of testosterone, which is often associated with visceral obesity. (See "Pathophysiology and causes of hirsutism".)
HEALTH CARE COSTS OF OBESITY — The treatment of obesity and obesity-related conditions represents an enormous economic burden [43,86-90]. In addition to direct health care expenses, there are other costs, including lost work productivity and lower household income; in 2017, obesity cost the United States an estimated USD $1.4 trillion [91].
In the Swedish Obesity Study, individuals with obesity were three times as likely to draw a disability pension, used twice the number of sick days, and had higher annual drug costs compared with individuals without obesity [92].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obesity in adults".)
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 5th to 6th 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 10th to 12th 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.)
●Basics topics (see "Patient education: Weight loss treatments (The Basics)" and "Patient education: Health risks of obesity (The Basics)")
●Beyond the Basics topics (see "Patient education: Losing weight (Beyond the Basics)" and "Patient education: Weight loss surgery and procedures (Beyond the Basics)")
SUMMARY
●Obesity is associated with significant excess morbidity and mortality. There are over 230 comorbidities associated with obesity. (See 'Mortality' above and 'Morbidity' above.)
●In general, greater body mass index (BMI), calculated as weight (in kg) divided by height (in m2), is associated with increased rate of death from all causes and from cardiovascular disease (CVD) (figure 1). (See 'Mortality' above.)
●Specifically, obesity and increased central fat are associated with diabetes mellitus, hypertension, heart disease, stroke, sleep apnea, and many chronic and debilitating diseases. Even modest weight loss improves these comorbidities. (See 'Morbidity' above.)
●Obesity affects psychosocial function as individuals with obesity are often exposed to public disapproval. This stigma is seen in education, employment, and health care, among other areas. (See 'Stigma of obesity' above.)
●Treating obesity and obesity-related conditions represents an enormous economic burden. In addition to direct health care expenses, there are other costs, including lost work productivity and lower household income. (See 'Health care costs of obesity' above.)
●The management of obesity is discussed in detail elsewhere. (See "Obesity in adults: Overview of management".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges George Bray, MD, who contributed to an earlier version of this topic review.
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38 : Obesity and mortality.
39 : Fitness vs. fatness on all-cause mortality: a meta-analysis.
40 : Fitness and fatness as predictors of mortality from all causes and from cardiovascular disease in men and women in the lipid research clinics study.
41 : Adiposity as compared with physical activity in predicting mortality among women.
42 : Obesity.
43 : Health and economic burden of the projected obesity trends in the USA and the UK.
44 : Health Benefits of Long-Term Weight-Loss Maintenance.
45 : Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the National Health and Nutrition Examination Survey, 1999 to 2004.
46 : Impact of overweight on the risk of developing common chronic diseases during a 10-year period.
47 : Guidelines for healthy weight.
48 : Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
49 : Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss.
50 : Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.
51 : Clinical implications of obesity with specific focus on cardiovascular disease: a statement for professionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: endorsed by the American College of Cardiology Foundation.
52 : Adiposity of the heart, revisited.
53 : Dynamic relationship between the slow potential and spikes in cockroach ocellar neurons.
54 : Vital Signs: Trends in Incidence of Cancers Associated with Overweight and Obesity - United States, 2005-2014.
55 : Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality.
56 : Insights into the relationships between diabetes, prediabetes, and cancer.
57 : Adiposity and cancer at major anatomical sites: umbrella review of the literature.
58 : Quantitative association between body mass index and the risk of cancer: A global Meta-analysis of prospective cohort studies.
59 : Body mass index, abdominal fatness and the risk of gallbladder disease.
60 : The adverse effects of obesity on conception and implantation.
61 : Obesity and prevalent and incident CKD: the Hypertension Detection and Follow-Up Program.
62 : Body mass index and risk for end-stage renal disease.
63 : Obesity, albuminuria, and urinalysis findings in US young adults from the Add Health Wave III study.
64 : Overweight, obesity, and the development of stage 3 CKD: the Framingham Heart Study.
65 : Obesity, weight gain, and the risk of kidney stones.
66 : Metabolically healthy and unhealthy obesity phenotypes and risk of renal stone: a cohort study.
67 : Perceived weight discrimination in the CARDIA study: differences by race, sex, and weight status.
68 : Obesity Discrimination in the Recruitment Process: "You're Not Hired!".
69 : Meta-analysis of the association between body mass index and health-related quality of life among adults, assessed by the SF-36.
70 : Depression in association with severe obesity: changes with weight loss.
71 : Obesity and infection.
72 : In the clinic: obesity.
73 : Obesity and serious infections.
74 : A case-control study of risk factors for wound infection in a colorectal unit.
75 : Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study.
76 : Obesity and susceptibility to severe outcomes following respiratory viral infection.
77 : Association between body mass index and laboratory-confirmed influenza in middle aged and older adults: a prospective cohort study.
78 : Obesity in Patients Younger Than 60 Years Is a Risk Factor for COVID-19 Hospital Admission.
79 : Obesity in Patients Younger Than 60 Years Is a Risk Factor for COVID-19 Hospital Admission.
80 : High prevalence of obesity among adult inpatients wtih severe COVID-19 in initial and validation population; a cross sectional French study
81 : High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation.
82 : Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection : A Retrospective Cohort Study.
83 : Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization.
84 : Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships.
85 : The obesity syndrome and acanthosis nigricans. Acanthosis nigricans is a common cosmetic problem providing epidemiological clues to the obesity syndrome, the insulin-resistance syndrome, the thrifty metabolism, dyslipidaemia, hypertension and diabetes mellitus type II.
86 : The lifetime medical cost burden of overweight and obesity: implications for obesity prevention.
87 : Obesity and the risk of new-onset atrial fibrillation.
88 : Obesity, health services use, and health care costs among members of a health maintenance organization.
89 : Relation of body mass index in young adulthood and middle age to Medicare expenditures in older age.
90 : Obesity: preventing and managing the global epidemic. Report of a WHO consultation.
91 : Obesity: preventing and managing the global epidemic. Report of a WHO consultation.
92 : Pharmaceutical costs in obese individuals: comparison with a randomly selected population sample and long-term changes after conventional and surgical treatment: the SOS intervention study.
