The medical complications of obesity

The prevalence of overweight and obesity is increasing worldwide. 1 A comparison of data from 1976–80 2 with that from 1999–2000 shows that the prevalence of overweight (defined as body mass index, BMI, of 25–29.9 kg/m 2 ) increased from 46% to 64.5%, and the prevalence of obesity (BMI ⩾ 30 kg/m 2 ) doubled to 30.5%. The epidemic of obesity is not just isolated to the US, but is worldwide, 3,4 including less affluent countries. 4 Obesity and overweight have many causes, including genetic, metabolic, behavioural and environmental. The rapid increase in prevalence suggests that behavioural and environmental influences predominate, rather than biological changes. We summarize data from many studies evaluating the impact of obesity on mortality and morbidity, discuss some controversies and provide practical guidelines for managing obese patients. Direct associations between obesity and several diseases, including diabetes mellitus, hypertension, dyslipidaemia and ischaemic heart disease, are well recognized. Despite this, the relationship between body weight and all-cause mortality is more controversial. A very high degree of obesity (BMI ⩾35 kg/m 2 ) seems to be linked to higher mortality rates, 5 but the relationship between more modest degrees of overweight and mortality is unclear. Initial data from actuarial studies of more than 4 million men and women showed a direct positive association between body weight and overall mortality rates. 6 Subsequent studies confirmed increased mortality risk above a certain threshold, but found a U-shaped association between weight and mortality. 7,8 In the Build study, 9 there was a higher mortality in lean subjects, but there was no adjustment for smoking. The American Cancer Society found a much stronger association between leanness and mortality, specifically cancer mortality, in the group of smokers compared to non-smokers. 10 The Harvard Alumni Study 11 was a prospective cohort study of more than 19 000 middle-aged men. It also noted a U-shaped relation between BMI and mortality after adjustment for age, cigarette smoking and physical activity. However, after excluding those who had ever smoked and those who died within the first 5 years of follow-up, there was no evidence for increased mortality in those with a BMI <22.5 kg/m 2 and the lowest mortality was noted in those who weighed 20% below the average. A direct relationship between BMI and mortality was also described in a cohort of more than 8000 Seventh Day Adventists, with the lowest mortality rate found in men with a BMI <22.3 kg/m 2 . 12 This group is usually lean by choice, and therefore their leanness is less likely to be the result of cigarette smoking or underlying illness. Obesity has also been associated with an increased risk of mortality in women. There have been some reports that did not find a relationship between BMI and mortality in women, 13–15 but due to the small number of endpoints occurring in these cohorts, these studies lacked sufficient power. Several larger studies showed a significant association between body weight 8–10 or BMI and mortality. 16 Notably, the Nurses’ Health Study, showed a U-shaped relationship between BMI and all-cause mortality. 16 Another recent study found a U-shaped association between weight and mortality in a large cohort of Chinese men and women. 17 There are several explanations for the discrepancies observed in the above epidemiological studies. There may be an adverse effect of leanness and leanness can be a surrogate marker of underlying diseases. 18 The possibility that there may be some beneficial effect of mild degree of excess body weight on overall survival, also cannot be entirely ruled out. For example, in the INTERHEART study, high hip circumference had a negative predictive value for myocardial infarction, while high waist circumference was associated with high rates of myocardial infarction, implying that considering only the BMI and ignoring fat distribution may be misleading. 19 Weight or BMI may be relatively low in an elderly person with little lean body mass relative to adipose tissue. The correlations between BMI and more direct measures of adiposity (e.g. underwater weighing) range between 0.6 and 0.8. 20,21 Furthermore, reported correlations between waist–hip ratios and visceral adipose tissue volume (as assessed by CT) are imperfect. 22 Other limitations of several epidemiological studies are: partial adjustment for confounding factors (such as physical fitness, type of diet, family history, weight cycling, use of diet drugs, economic status), inclusion of self-reported data, not taking into account the age of onset of obesity and not estimating the obesity-attributable mortality. It has been estimated that the excess mortality associated with obesity in the Framingham study is due to the effect of weight cycling, and that participants with stable body weights were not at increased risk. 23 A similar finding has been reported in the National Health and Nutrition Examination Survey (NHANES). 24 Flegal et al. recently made an estimation of relative risks of mortality associated with different levels of BMI from the nationally representative NHANES I, II and III, and applied these relative risks to the distribution of BMI and other covariates from NHANES 1999–2002 data to estimate attributable fractions and number of excess deaths related to obesity. 25 After adjusting for confounding factors and for effect modification by age, they found an increased mortality associated both with being underweight and with being obese. Notably, the increased mortality was found in subjects with a BMI ⩾35 kg/m 2 , but there was no increase in mortality in the in the less obese groups. In addition, there was a decline in the relative risk of mortality according to BMI categories from NHANES I to NHANES III. This finding suggests that the attenuation in the strength of the association between obesity and mortality is related to the improvement in the standard medical care that has resulted in reduced cardiovascular mortality in recent years. Age-adjusted death rates from heart disease (per 100 000 population) declined from 412.1 in 1980 to 240.8 in 2002. 26 In addition, there was a decrease in the prevalence of hypercholesterolemia and smoking, but not of diabetes, between 1960–62 and 1999–2000. 27 These changes occurred despite the marked increase in the prevalence of obesity during this time period. There is a strong association between obesity and type 2 diabetes mellitus, in both genders and all ethnic groups. Data from the Nurses’ Health Study showed an age-adjusted relative risk of 40 for diabetes in women with a BMI ⩾31 kg/m 2 , compared with women with a BMI <22 kg/m 2 . 28 A similar risk was shown for men in the Health Professionals Follow-up Study: a BMI of ⩾35 kg/m 2 was associated with an age-adjusted relative risk for diabetes of 60.9, compared with a BMI of 30 kg/m 2 was associated with a hazard ratio of 8.29 for developing diabetes, compared to those men with a BMI <25 kg/m 2 and a fasting plasma glucose 30 kg/m 2 ) had a mortality ratio of compared to a group of BMI on This has been the obesity noted obesity is linked to hypertension, disease, diabetes mellitus, and and heart are all strongly linked to Despite the relationship between obesity and several of the risk factors for a relationship between and obesity has only recently been studies as to is linked to obesity. This may be due to follow-up, to account for cardiovascular of Data from the Framingham Study a between the risk of developing and In adjusting for myocardial or heart increase of 1 in BMI was associated with a increase in the risk of In addition, there was a increase in as BMI The relationship between BMI and was not significant after adjusting for a between obesity and In there is an association between and and as be obesity and are Obesity is linked to an increased risk of in both men and women. In a study of men an hazard of for ischaemic was found for 1 increase in In the Health Study of those with a BMI kg/m 2 had a relative risk of for an ischaemic and for a 1 increase in BMI resulted in a increase in the relative risk for In a study from of men a BMI >30 kg/m 2 resulted in a hazard ratio of for ischaemic but not In these the increased risk for after adjusting for risk factors as hypertension, diabetes and women also have an increased risk for Data from the Health Study of women with self-reported weight and found a ratio of for ischaemic in women with BMI >30 kg/m 2 compared to those with BMI <25 kg/m 2 . There was no significant relationship between BMI and were found in women in the Nurses’ Health In this study there was a relationship between obesity and It is there is no relationship between and but may be linked to the number of in of the compared to ischaemic However, not all studies have shown an association between BMI and and recent data that fat is a stronger risk factor for than overall obesity. In a report from the Study of body fat was a of mortality, of BMI, smoking, and diabetes Obesity is a risk factor for of with are reported to be of body evidence from the Study showed that risk increased with obesity. A circumference is with has also been with In addition, weight can Obesity to fat in the in obese may on the fat may increase and with the of the and that also after weight in obese with The prevalence of is increased in overweight subjects, and obese or overweight subjects account for of for studies that obesity and that the relative risk of with increasing obesity. In addition, obese subjects after weight of Obesity also appears to be a risk factor for The relationship between obesity and is underlined by the finding that obesity is a strong of the of into 5 for this relationship changes in and other factors that and the relationship between and obesity has been in the cohort in This group men and 11 women years. 1 and were and the of the ratio in both men and women, and this relation after adjustment for This suggests that obesity may and more than obesity. Furthermore, a of a of studies of or showed a and also a to with increasing BMI, to was not by disease is a that has been linked to obesity. studies this association in studies in the US, and and of these studies showed a increase in as BMI However, large studies did not find Several studies have the relationship between and reported a positive reported no and found a positive association in women but not in men. 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For both men and women, increasing BMI was associated with higher death rates due to of the and and were also at increased risk for death from and while women were at increased risk of death from of the and the of these data, the estimated that overweight and obesity in the account for of all cancer deaths in men and 20% in women. In a and from the evaluating data on million deaths from million were attributable to risk including overweight and obesity. 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Obesity during is associated with an increased risk of including diabetes, and as and higher rates of and obesity may also be an risk factor for and mortality. 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The epidemic of obesity in the has been associated with an increase in the prevalence of It is obesity is a risk factor of diabetes and hypertension. NHANES the risk of disease or death was associated with a BMI kg/m 2 , with a relative risk of those obese compared with weight but risk was not increased for those as overweight or obese. In the Framingham study, who were obese at baseline were more likely to have a decrease in estimated rate increased baseline BMI was associated with to disease, with an ratio of for standard Notably, weight may In a study of 24 type 1 and type 2 with a in BMI from to 26 kg/m 2 was associated with a decrease in from to 24 and an improvement in from to 2 . Despite the mortality and associated with obesity described in are well of the of the obese that of obese obese are Several studies have shown that low physical and physical are for all-cause mortality, mortality and cardiovascular in lean and obese men and women. In the Study, lean men had a higher risk for all-cause and mortality than men who were and obese. In a prospective study of men and women, low time physical and physical fitness, but not high BMI, were of all-cause and mortality. in study in men and women, physical fitness, associated with reduced mortality from did not the increased risk associated with obesity. of the by increased physical and can risk and all-cause mortality is by In both and Pima Indians, is positively with Other of physical improvement of dyslipidaemia and increased and The of physical and that at a of physical and as of the risks associated with obesity. and the are strongly associated with increased risk for type 2 diabetes, and mortality in large epidemiological studies. 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It found that waist–hip ratio was to BMI, a and significant association with myocardial that after adjusting for the other risk BMI, in showed only a modest in some but not all and the association was not significant after This study to different the of that measures of waist or waist–hip ratio are related with risk. waist–hip ratio is a surrogate of increased visceral adipose tissue to be more and all to In a study of 1 kg visceral fat at with there was a significant improvement in in those who the while of tissue had no effect on of visceral fat by waist–hip ratio be of the of the obese The is to a in diseases. Obesity is associated with many and an between obesity and a positive family has been shown in several of these associated In with a strong family of diabetes and increased BMI, reduced to the associated with obesity was increasing the risk for developing type 2 diabetes. 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In addition, of medical care may the effect of obesity on The economic of this medical care to increasing of obese subjects cannot be all obese of physical and fitness, fat and family of diseases, can the obese person who is at increased risk. The age of onset of obesity also to be into as the risk of developing is higher in compared with obesity. 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