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The effect of obesity on health outcomes
Molecular and Cellular Endocrinology 316 (2010) 104–108
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Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce
Review
The effect of obesity on health outcomes John B. Dixon a,b,∗ a b
School of Primary Health Care, Monash University, Melbourne, Australia Baker-IDI Heart and Diabetes Institute, Melbourne, Australia
a r t i c l e
i n f o
Article history: Received 1 January 2009 Received in revised form 30 June 2009 Accepted 13 July 2009 Keywords: Health outcome Burden of disease Quality of life Economic Review
a b s t r a c t The prevalence of obesity has progressively increased globally over the last 30 years. The determinants of this pandemic are many, poorly defined and priorities debated. While public health measures to prevent obesity have largely failed we are presented with a growing burden of disease and disability. Cardiovascular disease, type-2 diabetes, obesity related cancers, osteoarthritis and psychological disturbance generate much of the morbidity and years of life lost associated with increasing levels of obesity. Obesity has a clearly measurable impact on physical and mental health, health related quality of life, and generates considerable direct and indirect costs. The evolving obesity pandemic is exacting a considerable toll on those affected, the treating health services, and on our communities. Weight loss appears to be the most effective therapy for obesity and obesity related comorbidity. As health care researchers and providers we are likely to play a peripheral role in the prevention of obesity, but a central role in effectively treating those afflicted by the obesity pandemic. © 2009 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cardiovascular disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physical impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychological issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality of life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The economic burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Background There has been a steady increase in the prevalence of obesity over the last 30 years with developed countries leading the way. Unfortunately, developing countries are following suit as they urbanize and modernize. More than 300 million people worldwide now exceed the body mass index (BMI) obesity threshold of 30 kg/m (Kelly et al., 2008). Almost one-third of the US adult population are obese, and this proportion is expected to continue to increase
∗ School of Primary Health Care, Monash University, 270 Ferntree Gully Road, Notting Hill 3168, Australia. Tel.: +61 3 9501 2431; fax: +61 3 8575 2233. E-mail address: [email protected]. 0303-7207/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2009.07.008
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(Ogden et al., 2006; Wang et al., 2008). In Australia, prevalence rates are 19% and 22% for adult men and women respectively (Thorburn, 2005). The major determinants driving obesity are complex, but clearly involve new or altered interactions with our environment, particularly related to food supply, eating behaviors, family-work culture and practices, socio-economic status, urban design and public policy. There is also increasing evidence of important interactions between our environment and our genes, possibly resulting in harmful metabolic programming and epigenetic changes beginning in-utero. While much has changed in the last 30 years, there is a need to have clear knowledge about the modifiable determinants of this emerging pandemic, so that effective preventative strategies can be waged. Health care providers, although quite peripheral to
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Table 1 The relative risk of some of the comorbidities, conditions and risks associated with obesity. Relative risk >5
Relative risk 2–5
Relative risk 1–2
Type-2 diabetes Dyslipidemia Obstructive sleep apnea
All-cause mortality Hypertension Myocardial infarction and stroke Endometrial carcinoma in women and hepatoma in men Gallstones and complications, incl. cancer Polycystic ovary syndrome Osteoarthritis (knees)
Cancer mortality Breast cancer Prostate and colon cancer in men Impaired fertility
Breathlessness
Excessive daytime sleepiness
Obesity hypoventilation syndrome Idiopathic intracranial hypertension Nonalcoholic steatohepatitis
Gout
Obstetric complications, incl. fetal abnormalities Asthma Gastroesophageal reflux Anesthetic risk Fig. 1. The metabolic syndrome: a metabolic and inflammatory cascade.
the key changes in our communities that are likely to prevent obesity; are increasingly confronted and overwhelmed by the health issues driven by overweight and obesity. The relative risk of many of the comorbidities of obesity in obese subjects is shown in Table 1. Obesity is associated with a broad range of health issues ranging from specific diseases such as type-2 diabetes and hypertension, to impaired quality of life, psychosocial disturbance, and limited access to quality care. A true obesity comorbid disease should satisfy three important characteristics: (1) It should increase in frequency and severity with adiposity. (2) There should be a plausible explanation for its association with obesity. (3) It should improve or resolve with weight loss. Classification of body weight is generally based on body mass index (BMI) which, of course, is not a measure fatness. While it provides a useful surrogate for total adiposity, BMI classification is further significantly influenced by, and needs adjustment for, age, gender, and ethnicity. Obesity is a condition of chronic nutrient overload and much of the obesity related disease risk is associated with the regional distribution of the resultant adiposity. Central, especially visceral, distribution of fat is associated with a metabolic and inflammatory cascade providing a toxic milieu that appears to drive many of the endocrine, cardiovascular and malignant consequences of obesity. On the other hand preferential peripheral fats distribution appears to be protective. Indeed, an Australian study of nearly 10,000 people, found that waist/hip ratio is better than waist circumference and BMI at predicting the future risk of dying from cardiovascular disease (Welborn et al., 2003). Fig. 1 shows, in a naïve way, how excessive central obesity acts through multiple putative mechanisms to drive a broad range of diseases all often linked to one another and requiring a focus on weight management as a central part of overall therapy. Many aspects of these will be described in detail in other manuscripts that appear in this supplement. 2. Mortality It is estimated that there are more than 300,000 annual deaths attributed to overweight and obesity in the USA and 80% of these are in subjects with a BMI greater than 30 (Allison et al., 1999). The relationship between BMI and mortality is generally a U-shaped curve with increased mortality at both lower and higher levels (Calle et al., 1999; Gu et al., 2006; Jee et al., 2006). The nadir appears to vary with ethnicity and age, and may be close to 25 kg/m2 for an adult
Caucasian population (Flegal et al., 2005). Mortality risk increases progressively with increasing BMI within the BMI range above 30 (Calle et al., 1999; Gu et al., 2006; Jee et al., 2006). The actual risk of death associated with obesity increases with age and BMI (Byers and , 2006), but the estimated years of life lost as a result of obesity are greatest in obese younger adults (Fontaine et al., 2003). Analysis of the Framingham heart follow-up study found that 40-year-old female nonsmokers lost 7.1 years and 40-year-old male nonsmokers lost 5.8 years because of obesity (Peeters et al., 2003). Causes of increased mortality related to overweight and obesity include: cardiovascular disease, diabetes and kidney disease, and obesity related cancer deaths (Flegal et al., 2007). Sustained weight loss through bariatric surgery has been shown to reduce all-cause mortality and in particular deaths related to cardiac disease, diabetes and cancer (Adams et al., 2007; Sjostrom et al., 2007). 3. Cardiovascular disease There are many components of the obesity related metabolic and inflammatory state that predispose to atherosclerosis and these include the more traditional elements of hypertension, type-2 diabetes and impaired glucose tolerance, and dyslipidemia characterized by raised triglycerides, low HDL-cholesterol and a small LDL particle phenotype (Tchernof et al., 1996; Lamarche et al., 1999). Other components include markers of systemic inflammation and oxidative stress including raised C-reactive protein, plasminogen activation inhibitor-1, sialic acid and von Willibrands factor (Berg and Scherer, 2005; Ashrafian et al., 2008). At an endothelial level there are increased levels of circulation adhesion molecules; E-selectin, P-selectin and intracellular adhesion molecule-1. Endothelial dependent vasodilatation is impaired with obesity, especially visceral obesity (Arcaro et al., 1999). There are also adipocyte derived adipokine changes, such as increased leptin and resistin, and reduced adiponectin that are associated with adverse effects on atherosclerosis. There are ongoing arguments about whether the various elements of the metabolic syndrome contribute in a synergistic way to predict major cardiac events, but there is no doubt about the clinical relevance of the clustered abnormalities and the benefits of weight loss (Despres, 2006). Obesity also impacts cardiovascular function increasing the risk of cardiac failure. Analysis of the Framingham study data shows a doubling of the risk of cardiac failure with a grade increase from obesity classes I to III (Kenchaiah et al., 2002). Increased obesity related cardiac output, hypertension, metabolic dysregulation and oxidative stress, obstructive sleep apnea, increased epicardial fat,
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and myocardial fatty infiltration all contribute to the eccentric and concentric hypertrophy characteristic of obesity related cardiac failure. Obesity cardiomyopathy is independent of the cardiac effects of hypertension, diabetes and atherosclerosis and is often poorly recognized (Wong and Marwick, 2007). Obesity also presents an unexplained paradox in relation to cardiac failure, established coronary heart disease, peripheral vascular disease and hemodialysis: overweight and class I obese patients fare better and survive longer than those who are underweight or of normal weight (Lavie et al., 2003, 2009; Schmidt and Salahudeen, 2007). 4. Cancer There is a clear association between increasing BMI and the incident risk of many common and rarer cancers. There is a graded increased mortality from cancer with increasing BMI. On the basis of associations observed in 2003 it was estimated that overweight and obesity in the United States could account for 14% of all deaths from cancer in men and 20% of those in women (Calle et al., 2003). A recent thorough systematic review found that in men BMI was strongly associated with oesophageal adenocarcinoma and thyroid, colon, and renal cancers. In women there were strong associations with endometrial, gallbladder, oesophageal adenocarcinoma, and renal cancers. There was also a strong relationship with both premenopausal and postmenopausal breast cancers in women from the Asia–Pacific region (Renehan et al., 2008). 5. Diabetes Obesity and type-2 diabetes are likely to be the two greatest public health problems of the coming decades (Zimmet et al., 2001). The WHO estimates in 2000 that worldwide there were 171 million people with diabetes and this will more than double to 366 million by 2030. In 2000 the greatest burden of diabetes was in India (40 million), followed by China (21 million), and USA (18 million), with disproportionately higher future increases expected in developing countries (WHO, 2008; King et al., 1998). The adjusted relative risk of developing type-2 diabetes, in the USA, with a body mass index (BMI) of greater than 35 kg/m2 is 93 for women (Colditz et al., 1995) and 42 for men (Chan et al., 1994) compared to those with a BMI <22 and <23 kg/m2 respectively. Weight gain and waist gain are also major factors with 1 kg weight gain over 10 years increasing the risk of type-2 diabetes by 7.3%. Fifty-six percent of the cases of type-2 diabetes in the Health Professionals Follow-up Study could be attributed to a weight gain of 7 kg or greater and 20% to a waist gain of 2.5 cm or greater (Koh-Banerjee et al., 2004). Many Asian and indigenous ethnic groups achieve these high levels of risk at lower BMI. Approximately half of those diagnosed with type-2 diabetes in the US are obese (Leibson et al., 2001). In addition the increases in diabetes prevalence over recent decades in developed countries have been disproportionately comprised of persons with extreme levels of obesity (Gregg et al., 2007). A substantial portion of the health costs attributed to obesity is related to type-2 diabetes. The socio-economic impact of type2 diabetes and its complications are substantial to individuals, their families and to society (Anon., 2008a). In particular, it is an inexorably progressive disease leading to deterioration in multiple organs and systems, and is the commonest cause for adult blindness, limb amputations and renal failure in western communities as well as the leading independent risk factor for coronary artery disease (NIDDK, 2004). The effects of substantial weight loss in obese subjects with type-2 diabetes are now teaching us a great deal about the mechanisms underlying the relationship between obesity and type-2 diabetes (Taylor, 2008).
6. Physical impairment There is a positive association between musculoskeletal disorders, physical disability and osteoarthritis, and the level of obesity. The prevalence of doctor diagnosed arthritis is 31% for obese adults and 16% for the non-obese (Arthritis related statistics, 2006). Obesity is associated with major mobility problems and pain reducing quality of life (Han et al., 1998; Barofsky et al., 1998). Obesity is related strongly to limitations in activities of daily living and to activities related to mobility (Himes, 2000). Physical constraints can make personal hygiene and cleanliness difficult with simple tasks such as drying oneself after a shower, cutting toenails or tying shoe laces major logistical tasks. In obese women the degree of disability is more closely related to lower body pain, rather than to BMI or age. Obese women report that their main mobility disturbances are those associated with strain and pain at work, sport, walking outdoors and up stairs. They also report difficulty with housework requiring squatting, stooping or lifting, and getting up from low chairs (Larsson and Mattsson, 2001). Common examples of musculoskeletal pain experienced by obese people include lower limb pain, especially in the feet and knees following periods of standing and walking, nagging lower back pain (Brown et al., 2000), and neck and shoulder pain suffered by women with large breasts (Netscher et al., 2000). There is a strong relationship between obesity and the development and progression of knee osteoarthritis, especially in women. An association with osteoarthritis at other sites including hips and hands, and obesity has been positive in some studies. The proportion of osteoarthritis attributable to obesity in middle aged women is 63% (Cicuttini and Spector, 1998). A combination of both mechanical and metabolic factors may be responsible for the relationship (Cicuttini and Spector, 1998). Modest weight loss in association with moderate physical activity improves physical function, pain, and performance in older obese adults with knee osteoarthritis (Messier et al., 2004). 7. Psychological issues Obesity of increasing severity is associated with a broad range of psychological and social burden most notable in younger women. Poor body image and self-esteem, binge eating disorder, depression, anxiety and psychological disturbance are common, and as with obesity related metabolic disorders, tend to cluster in those most susceptible individuals (Colles et al., 2008; Dixon et al., 2003; Wadden et al., 2006). There is also a positive relationship between increasing obesity and depression in older subjects with poor health, chronic disease and functional disability (Roberts et al., 2003; Onyike et al., 2003). This is consistent with the findings of depression in groups with chronic diseases including arthritis, cardiovascular disease, cancer and diabetes (Chapman et al., 2005). Depression is also associated with an inflammatory state and poorer outcomes in those with heart disease and diabetes (Marcus et al., 1992; Ladwig et al., 2003). As for other chronic illness, there is a tendency for physicians to ascribe symptoms of depression in the obese subject to the patient’s physical condition, possibly leading to under recognition and at times, inappropriate management of depression (Chapman et al., 2005). Clearly the mental health issues of chronically ill obese subjects need to be carefully considered, diagnosed and treated appropriately. As with other obesity related comorbidity there is generally a marked improvement in psychological comorbidity with substantial weight loss (Dixon et al., 2003, 2002).
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8. Quality of life Increasing the level of obesity has a major impact on patients’ physical, mental, psychosocial and economic health. These understandably have an impact on the patient’s health related quality of life and from the patients’ perspective quality of life is arguably the most important reason for seeking any medical intervention (Katz et al., 2000; Doll et al., 2000; Dixon et al., 2001). It has been estimated that obesity has a greater negative impact on quality of life than 20 years of aging (Sturm, 2002a). The negative impact on quality of life remains after accounting for demographics, health habits, medical conditions and depression (Katz et al., 2000). There are now many studies which have consistently shown substantially improved quality of life following weight loss (Dixon et al., 2001; Karlsson et al., 1998; Samsa et al., 2001). 9. The economic burden The economic burden of obesity is considerable and rising. In 1995 it was estimated that overweight, obesity and inactivity generated 9.4% of direct health costs in the US (Colditz, 1999). Healthcare expenditure for obesity in the US is an estimated additional $395 per person per year, and estimated total direct medical costs are $75 billion (2003 values), corresponding to approximately 4% of all adult healthcare expenditure (Sturm, 2002b; Finkelstein et al., 2005). In the (UK 2003–2004) overweight and obesity was responsible for 7.3% of morbidity and mortality and 4.6% of the NHS budget (Allender and Rayner, 2007). Estimates for mainland China (2003) are 3.7% of all health expenditure (Zhao et al., 2008) and for Switzerland (2002) 2.3–3.5% (Schmid et al., 2005). In Australia, as measured with disability adjusted life years, deaths and burden of disease related to overweight and obesity are largely related to comorbidity, with diabetes (40%), coronary artery disease (34%) and stroke (11%) leading the load, and with cancer and osteoarthritis additional contributors (AIHW, 2007). Indirect societal costs of obesity are also high due to increased absenteeism (Cawley et al., 2007; Jans et al., 2007) and workplace injuries (Pollack and Cheskin, 2007), disability payments, and loss of productivity (‘presenteeism’) (Schmier et al., 2006; Ricci and Chee, 2005). Access Economics estimated the cost of obesity in Australia in 2008 to be $A 8.28 billion, made up of loss of productivity $3.6 billion (44%), health system $2.0 billion (24%) and carer costs $1.9 billion (23%) (Anon., 2008b). Substantial weight loss through bariatric surgery is cost effective and reduces health costs associated with obesity and obesity related disease (Clegg et al., 2003; Salem et al., 2008). In fact surgery may provide health cost savings (Cremieux et al., 2008). 10. Conclusion The evolving obesity pandemic is exacting a considerable toll on those affected, the treating health services, and on our communities. It has a clearly measurable impact on physical and mental health, quality of life, and generated considerable direct an indirect cost. Weight loss appears to be the most effective therapy for obesity and obesity related comorbidity. Unfortunately health care providers are likely to play a peripheral role in the prevention of obesity, but a central role effectively treating those afflicted by the obesity pandemic. References Adams, T.D., Gress, R.E., Smith, S.C., et al., 2007. Long-term mortality after gastric bypass surgery. N. Engl. J. Med. 357, 753–761. AIHW, The Burden of disease and injury in Australia 2003, 2007.
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Ricci, J.A., Chee, E., 2005. Lost productive time associated with excess weight in the U.S. workforce. J. Occup. Environ. Med./Am. Coll. Occup. Environ. Med. 47, 1227–1234. Roberts, R.E., Deleger, S., Strawbridge, W.J., et al., 2003. Prospective association between obesity and depression: evidence from the Alameda County Study. Int. J. Obes. Relat. Metab. Disord. 27, 514–521. Salem, L., Devlin, A., Sullivan, S.D., et al., 2008. Cost-effectiveness analysis of laparoscopic gastric bypass, adjustable gastric banding, and nonoperative weight loss interventions. Surg. Obes. Relat. Dis. 4, 26–32. Samsa, G.P., Kolotkin, R.L., Williams, G.R., et al., 2001. Effect of moderate weight loss on health-related quality of life: an analysis of combined data from 4 randomized trials of sibutramine vs placebo. Am. J. Manage. Care 7, 875–883. Schmid, A., Schneider, H., Golay, A., et al., 2005. Economic burden of obesity and its comorbidities in Switzerland. Sozial-und Praventivmedizin 50, 87–94. Schmidt, D., Salahudeen, A., 2007. The obesity-survival paradox in hemodialysis patients: why do overweight hemodialysis patients live longer? Nutr. Clin. Pract. 22, 11–15. Schmier, J.K., Jones, M.L., Halpern, M.T., 2006. Cost of obesity in the workplace. Scand. J. Work Environ. Health 32, 5–11. Sjostrom, L., Narbro, K., Sjostrom, C.D., et al., 2007. Effects of bariatric surgery on mortality in Swedish obese subjects. N. Engl. J. Med. 357, 741–752. Sturm, R., 2002a. The effects of obesity, smoking, and drinking on medical problems and costs. Obesity outranks both smoking and drinking in its deleterious effects on health and health costs. Health Aff. (Millwood) 21, 245–253. Sturm, R., 2002b. The effects of obesity, smoking, and drinking on medical problems and costs. Health Aff. (Millwood) 21, 245–253. Taylor, R., 2008. Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause. Diabetologia 51, 1781–1789. Tchernof, A., Lamarche, B., Prud’Homme, D., et al., 1996. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 19, 629–637. Anon., The growing cost of obesity in 2008, Access Ecomomics Report to Diabetes Australia: Access Economics, 2008, iv. Thorburn, A.W., 2005. Prevalence of obesity in Australia. Obes. Rev. 6, 187–189. Wadden, T.A., Butryn, M.L., Sarwer, D.B., et al., 2006. Comparison of psychosocial status in treatment-seeking women with class III vs. class I–II obesity. Surg. Obes. Relat. Dis. 2, 138–145. Wang, Y., Beydoun, M.A., Liang, L., et al., 2008. Will all Americans become overweight or obese? Estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring) 16, 2323–2330. Welborn, T.A., Dhaliwal, S.S., Bennett, S.A., 2003. Waist–hip ratio is the dominant risk factor predicting cardiovascular death in Australia. Med. J. Aust. 179, 580–585. WHO, 2008. http://www.who.int/diabetes/facts/world figures. Wong, C., Marwick, T.H., 2007. Obesity cardiomyopathy: diagnosis and therapeutic implications. Nat. Clin. Pract. 4, 480–490. Zhao, W., Zhai, Y., Hu, J., et al., 2008. Economic burden of obesity-related chronic diseases in Mainland China. Obes. Rev. 9 (Suppl. 1), 62–67. Zimmet, P., Alberti, K.G., Shaw, J., 2001. Global and societal implications of the diabetes epidemic. Nature 414, 782–787.
Contents lists available at ScienceDirect
Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce
Review
The effect of obesity on health outcomes John B. Dixon a,b,∗ a b
School of Primary Health Care, Monash University, Melbourne, Australia Baker-IDI Heart and Diabetes Institute, Melbourne, Australia
a r t i c l e
i n f o
Article history: Received 1 January 2009 Received in revised form 30 June 2009 Accepted 13 July 2009 Keywords: Health outcome Burden of disease Quality of life Economic Review
a b s t r a c t The prevalence of obesity has progressively increased globally over the last 30 years. The determinants of this pandemic are many, poorly defined and priorities debated. While public health measures to prevent obesity have largely failed we are presented with a growing burden of disease and disability. Cardiovascular disease, type-2 diabetes, obesity related cancers, osteoarthritis and psychological disturbance generate much of the morbidity and years of life lost associated with increasing levels of obesity. Obesity has a clearly measurable impact on physical and mental health, health related quality of life, and generates considerable direct and indirect costs. The evolving obesity pandemic is exacting a considerable toll on those affected, the treating health services, and on our communities. Weight loss appears to be the most effective therapy for obesity and obesity related comorbidity. As health care researchers and providers we are likely to play a peripheral role in the prevention of obesity, but a central role in effectively treating those afflicted by the obesity pandemic. © 2009 Elsevier Ireland Ltd. All rights reserved.
Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cardiovascular disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physical impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Psychological issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quality of life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The economic burden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Background There has been a steady increase in the prevalence of obesity over the last 30 years with developed countries leading the way. Unfortunately, developing countries are following suit as they urbanize and modernize. More than 300 million people worldwide now exceed the body mass index (BMI) obesity threshold of 30 kg/m (Kelly et al., 2008). Almost one-third of the US adult population are obese, and this proportion is expected to continue to increase
∗ School of Primary Health Care, Monash University, 270 Ferntree Gully Road, Notting Hill 3168, Australia. Tel.: +61 3 9501 2431; fax: +61 3 8575 2233. E-mail address: [email protected]. 0303-7207/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2009.07.008
104 105 105 106 106 106 106 107 107 107 107
(Ogden et al., 2006; Wang et al., 2008). In Australia, prevalence rates are 19% and 22% for adult men and women respectively (Thorburn, 2005). The major determinants driving obesity are complex, but clearly involve new or altered interactions with our environment, particularly related to food supply, eating behaviors, family-work culture and practices, socio-economic status, urban design and public policy. There is also increasing evidence of important interactions between our environment and our genes, possibly resulting in harmful metabolic programming and epigenetic changes beginning in-utero. While much has changed in the last 30 years, there is a need to have clear knowledge about the modifiable determinants of this emerging pandemic, so that effective preventative strategies can be waged. Health care providers, although quite peripheral to
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Table 1 The relative risk of some of the comorbidities, conditions and risks associated with obesity. Relative risk >5
Relative risk 2–5
Relative risk 1–2
Type-2 diabetes Dyslipidemia Obstructive sleep apnea
All-cause mortality Hypertension Myocardial infarction and stroke Endometrial carcinoma in women and hepatoma in men Gallstones and complications, incl. cancer Polycystic ovary syndrome Osteoarthritis (knees)
Cancer mortality Breast cancer Prostate and colon cancer in men Impaired fertility
Breathlessness
Excessive daytime sleepiness
Obesity hypoventilation syndrome Idiopathic intracranial hypertension Nonalcoholic steatohepatitis
Gout
Obstetric complications, incl. fetal abnormalities Asthma Gastroesophageal reflux Anesthetic risk Fig. 1. The metabolic syndrome: a metabolic and inflammatory cascade.
the key changes in our communities that are likely to prevent obesity; are increasingly confronted and overwhelmed by the health issues driven by overweight and obesity. The relative risk of many of the comorbidities of obesity in obese subjects is shown in Table 1. Obesity is associated with a broad range of health issues ranging from specific diseases such as type-2 diabetes and hypertension, to impaired quality of life, psychosocial disturbance, and limited access to quality care. A true obesity comorbid disease should satisfy three important characteristics: (1) It should increase in frequency and severity with adiposity. (2) There should be a plausible explanation for its association with obesity. (3) It should improve or resolve with weight loss. Classification of body weight is generally based on body mass index (BMI) which, of course, is not a measure fatness. While it provides a useful surrogate for total adiposity, BMI classification is further significantly influenced by, and needs adjustment for, age, gender, and ethnicity. Obesity is a condition of chronic nutrient overload and much of the obesity related disease risk is associated with the regional distribution of the resultant adiposity. Central, especially visceral, distribution of fat is associated with a metabolic and inflammatory cascade providing a toxic milieu that appears to drive many of the endocrine, cardiovascular and malignant consequences of obesity. On the other hand preferential peripheral fats distribution appears to be protective. Indeed, an Australian study of nearly 10,000 people, found that waist/hip ratio is better than waist circumference and BMI at predicting the future risk of dying from cardiovascular disease (Welborn et al., 2003). Fig. 1 shows, in a naïve way, how excessive central obesity acts through multiple putative mechanisms to drive a broad range of diseases all often linked to one another and requiring a focus on weight management as a central part of overall therapy. Many aspects of these will be described in detail in other manuscripts that appear in this supplement. 2. Mortality It is estimated that there are more than 300,000 annual deaths attributed to overweight and obesity in the USA and 80% of these are in subjects with a BMI greater than 30 (Allison et al., 1999). The relationship between BMI and mortality is generally a U-shaped curve with increased mortality at both lower and higher levels (Calle et al., 1999; Gu et al., 2006; Jee et al., 2006). The nadir appears to vary with ethnicity and age, and may be close to 25 kg/m2 for an adult
Caucasian population (Flegal et al., 2005). Mortality risk increases progressively with increasing BMI within the BMI range above 30 (Calle et al., 1999; Gu et al., 2006; Jee et al., 2006). The actual risk of death associated with obesity increases with age and BMI (Byers and , 2006), but the estimated years of life lost as a result of obesity are greatest in obese younger adults (Fontaine et al., 2003). Analysis of the Framingham heart follow-up study found that 40-year-old female nonsmokers lost 7.1 years and 40-year-old male nonsmokers lost 5.8 years because of obesity (Peeters et al., 2003). Causes of increased mortality related to overweight and obesity include: cardiovascular disease, diabetes and kidney disease, and obesity related cancer deaths (Flegal et al., 2007). Sustained weight loss through bariatric surgery has been shown to reduce all-cause mortality and in particular deaths related to cardiac disease, diabetes and cancer (Adams et al., 2007; Sjostrom et al., 2007). 3. Cardiovascular disease There are many components of the obesity related metabolic and inflammatory state that predispose to atherosclerosis and these include the more traditional elements of hypertension, type-2 diabetes and impaired glucose tolerance, and dyslipidemia characterized by raised triglycerides, low HDL-cholesterol and a small LDL particle phenotype (Tchernof et al., 1996; Lamarche et al., 1999). Other components include markers of systemic inflammation and oxidative stress including raised C-reactive protein, plasminogen activation inhibitor-1, sialic acid and von Willibrands factor (Berg and Scherer, 2005; Ashrafian et al., 2008). At an endothelial level there are increased levels of circulation adhesion molecules; E-selectin, P-selectin and intracellular adhesion molecule-1. Endothelial dependent vasodilatation is impaired with obesity, especially visceral obesity (Arcaro et al., 1999). There are also adipocyte derived adipokine changes, such as increased leptin and resistin, and reduced adiponectin that are associated with adverse effects on atherosclerosis. There are ongoing arguments about whether the various elements of the metabolic syndrome contribute in a synergistic way to predict major cardiac events, but there is no doubt about the clinical relevance of the clustered abnormalities and the benefits of weight loss (Despres, 2006). Obesity also impacts cardiovascular function increasing the risk of cardiac failure. Analysis of the Framingham study data shows a doubling of the risk of cardiac failure with a grade increase from obesity classes I to III (Kenchaiah et al., 2002). Increased obesity related cardiac output, hypertension, metabolic dysregulation and oxidative stress, obstructive sleep apnea, increased epicardial fat,
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and myocardial fatty infiltration all contribute to the eccentric and concentric hypertrophy characteristic of obesity related cardiac failure. Obesity cardiomyopathy is independent of the cardiac effects of hypertension, diabetes and atherosclerosis and is often poorly recognized (Wong and Marwick, 2007). Obesity also presents an unexplained paradox in relation to cardiac failure, established coronary heart disease, peripheral vascular disease and hemodialysis: overweight and class I obese patients fare better and survive longer than those who are underweight or of normal weight (Lavie et al., 2003, 2009; Schmidt and Salahudeen, 2007). 4. Cancer There is a clear association between increasing BMI and the incident risk of many common and rarer cancers. There is a graded increased mortality from cancer with increasing BMI. On the basis of associations observed in 2003 it was estimated that overweight and obesity in the United States could account for 14% of all deaths from cancer in men and 20% of those in women (Calle et al., 2003). A recent thorough systematic review found that in men BMI was strongly associated with oesophageal adenocarcinoma and thyroid, colon, and renal cancers. In women there were strong associations with endometrial, gallbladder, oesophageal adenocarcinoma, and renal cancers. There was also a strong relationship with both premenopausal and postmenopausal breast cancers in women from the Asia–Pacific region (Renehan et al., 2008). 5. Diabetes Obesity and type-2 diabetes are likely to be the two greatest public health problems of the coming decades (Zimmet et al., 2001). The WHO estimates in 2000 that worldwide there were 171 million people with diabetes and this will more than double to 366 million by 2030. In 2000 the greatest burden of diabetes was in India (40 million), followed by China (21 million), and USA (18 million), with disproportionately higher future increases expected in developing countries (WHO, 2008; King et al., 1998). The adjusted relative risk of developing type-2 diabetes, in the USA, with a body mass index (BMI) of greater than 35 kg/m2 is 93 for women (Colditz et al., 1995) and 42 for men (Chan et al., 1994) compared to those with a BMI <22 and <23 kg/m2 respectively. Weight gain and waist gain are also major factors with 1 kg weight gain over 10 years increasing the risk of type-2 diabetes by 7.3%. Fifty-six percent of the cases of type-2 diabetes in the Health Professionals Follow-up Study could be attributed to a weight gain of 7 kg or greater and 20% to a waist gain of 2.5 cm or greater (Koh-Banerjee et al., 2004). Many Asian and indigenous ethnic groups achieve these high levels of risk at lower BMI. Approximately half of those diagnosed with type-2 diabetes in the US are obese (Leibson et al., 2001). In addition the increases in diabetes prevalence over recent decades in developed countries have been disproportionately comprised of persons with extreme levels of obesity (Gregg et al., 2007). A substantial portion of the health costs attributed to obesity is related to type-2 diabetes. The socio-economic impact of type2 diabetes and its complications are substantial to individuals, their families and to society (Anon., 2008a). In particular, it is an inexorably progressive disease leading to deterioration in multiple organs and systems, and is the commonest cause for adult blindness, limb amputations and renal failure in western communities as well as the leading independent risk factor for coronary artery disease (NIDDK, 2004). The effects of substantial weight loss in obese subjects with type-2 diabetes are now teaching us a great deal about the mechanisms underlying the relationship between obesity and type-2 diabetes (Taylor, 2008).
6. Physical impairment There is a positive association between musculoskeletal disorders, physical disability and osteoarthritis, and the level of obesity. The prevalence of doctor diagnosed arthritis is 31% for obese adults and 16% for the non-obese (Arthritis related statistics, 2006). Obesity is associated with major mobility problems and pain reducing quality of life (Han et al., 1998; Barofsky et al., 1998). Obesity is related strongly to limitations in activities of daily living and to activities related to mobility (Himes, 2000). Physical constraints can make personal hygiene and cleanliness difficult with simple tasks such as drying oneself after a shower, cutting toenails or tying shoe laces major logistical tasks. In obese women the degree of disability is more closely related to lower body pain, rather than to BMI or age. Obese women report that their main mobility disturbances are those associated with strain and pain at work, sport, walking outdoors and up stairs. They also report difficulty with housework requiring squatting, stooping or lifting, and getting up from low chairs (Larsson and Mattsson, 2001). Common examples of musculoskeletal pain experienced by obese people include lower limb pain, especially in the feet and knees following periods of standing and walking, nagging lower back pain (Brown et al., 2000), and neck and shoulder pain suffered by women with large breasts (Netscher et al., 2000). There is a strong relationship between obesity and the development and progression of knee osteoarthritis, especially in women. An association with osteoarthritis at other sites including hips and hands, and obesity has been positive in some studies. The proportion of osteoarthritis attributable to obesity in middle aged women is 63% (Cicuttini and Spector, 1998). A combination of both mechanical and metabolic factors may be responsible for the relationship (Cicuttini and Spector, 1998). Modest weight loss in association with moderate physical activity improves physical function, pain, and performance in older obese adults with knee osteoarthritis (Messier et al., 2004). 7. Psychological issues Obesity of increasing severity is associated with a broad range of psychological and social burden most notable in younger women. Poor body image and self-esteem, binge eating disorder, depression, anxiety and psychological disturbance are common, and as with obesity related metabolic disorders, tend to cluster in those most susceptible individuals (Colles et al., 2008; Dixon et al., 2003; Wadden et al., 2006). There is also a positive relationship between increasing obesity and depression in older subjects with poor health, chronic disease and functional disability (Roberts et al., 2003; Onyike et al., 2003). This is consistent with the findings of depression in groups with chronic diseases including arthritis, cardiovascular disease, cancer and diabetes (Chapman et al., 2005). Depression is also associated with an inflammatory state and poorer outcomes in those with heart disease and diabetes (Marcus et al., 1992; Ladwig et al., 2003). As for other chronic illness, there is a tendency for physicians to ascribe symptoms of depression in the obese subject to the patient’s physical condition, possibly leading to under recognition and at times, inappropriate management of depression (Chapman et al., 2005). Clearly the mental health issues of chronically ill obese subjects need to be carefully considered, diagnosed and treated appropriately. As with other obesity related comorbidity there is generally a marked improvement in psychological comorbidity with substantial weight loss (Dixon et al., 2003, 2002).
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8. Quality of life Increasing the level of obesity has a major impact on patients’ physical, mental, psychosocial and economic health. These understandably have an impact on the patient’s health related quality of life and from the patients’ perspective quality of life is arguably the most important reason for seeking any medical intervention (Katz et al., 2000; Doll et al., 2000; Dixon et al., 2001). It has been estimated that obesity has a greater negative impact on quality of life than 20 years of aging (Sturm, 2002a). The negative impact on quality of life remains after accounting for demographics, health habits, medical conditions and depression (Katz et al., 2000). There are now many studies which have consistently shown substantially improved quality of life following weight loss (Dixon et al., 2001; Karlsson et al., 1998; Samsa et al., 2001). 9. The economic burden The economic burden of obesity is considerable and rising. In 1995 it was estimated that overweight, obesity and inactivity generated 9.4% of direct health costs in the US (Colditz, 1999). Healthcare expenditure for obesity in the US is an estimated additional $395 per person per year, and estimated total direct medical costs are $75 billion (2003 values), corresponding to approximately 4% of all adult healthcare expenditure (Sturm, 2002b; Finkelstein et al., 2005). In the (UK 2003–2004) overweight and obesity was responsible for 7.3% of morbidity and mortality and 4.6% of the NHS budget (Allender and Rayner, 2007). Estimates for mainland China (2003) are 3.7% of all health expenditure (Zhao et al., 2008) and for Switzerland (2002) 2.3–3.5% (Schmid et al., 2005). In Australia, as measured with disability adjusted life years, deaths and burden of disease related to overweight and obesity are largely related to comorbidity, with diabetes (40%), coronary artery disease (34%) and stroke (11%) leading the load, and with cancer and osteoarthritis additional contributors (AIHW, 2007). Indirect societal costs of obesity are also high due to increased absenteeism (Cawley et al., 2007; Jans et al., 2007) and workplace injuries (Pollack and Cheskin, 2007), disability payments, and loss of productivity (‘presenteeism’) (Schmier et al., 2006; Ricci and Chee, 2005). Access Economics estimated the cost of obesity in Australia in 2008 to be $A 8.28 billion, made up of loss of productivity $3.6 billion (44%), health system $2.0 billion (24%) and carer costs $1.9 billion (23%) (Anon., 2008b). Substantial weight loss through bariatric surgery is cost effective and reduces health costs associated with obesity and obesity related disease (Clegg et al., 2003; Salem et al., 2008). In fact surgery may provide health cost savings (Cremieux et al., 2008). 10. Conclusion The evolving obesity pandemic is exacting a considerable toll on those affected, the treating health services, and on our communities. It has a clearly measurable impact on physical and mental health, quality of life, and generated considerable direct an indirect cost. Weight loss appears to be the most effective therapy for obesity and obesity related comorbidity. Unfortunately health care providers are likely to play a peripheral role in the prevention of obesity, but a central role effectively treating those afflicted by the obesity pandemic. References Adams, T.D., Gress, R.E., Smith, S.C., et al., 2007. Long-term mortality after gastric bypass surgery. N. Engl. J. Med. 357, 753–761. AIHW, The Burden of disease and injury in Australia 2003, 2007.
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