Commentary: Understanding the epidemiology of overweight and obesity—a real global public health concern

Campos and his collaborators raise some useful and important questions about the way to understand the impact of overweight and obesity on health.1 Especially, bringing attention to some of the complexities in overweight/obesity and health relationships and covert financial interests involved in obesity research and related promotion activities is noteworthy. At the same time, however, they ignore some basic pathways linking dietary and physical activity patterns to weight dynamics to health. Furthermore, they selectively examine the literature and, as is easily done, arrive at the conclusion that there is much ado about nothing in the ‘obesity epidemic or pandemic’. A different reading of the way to study in a causal manner the role of these factors as they affect health provides us with a very different conclusion. Rapidly changing diets and reduced physical activity levels have led to a marked increase in the prevalence of diet-related chronic diseases in both developed and developing countries.2,3 The pathway linking weight status to health is complex. Figure 1 provides a simplified view of the major research relating the key factors in this pathway. How one studies this pathway clearly affects one's conclusions. The manner in which obesity fits into this causal pathway and the methods for studying this are at the core of the discussion. Considerable progress in the scientific study of obesity's determinants and consequences has led to a growing understanding of the responsible causal pathways, risk factors, and mechanisms. In particular, there is now strong evidence relating dietary factors and physical activity levels to the risk of obesity, hypertension, certain cancers, diabetes, stroke, and other coronary heart disease (CHD). Key pathways for diet, physical activity, and obesity on nutrition-related non-communicable diseases (note direction of effects are not presented) Much of the debate with Campos et al. lies in their selective use of research on these pathways and misunderstanding of basic epidemiological principles. Clearly there are a large number of ways that diet directly affects the health outcomes noted in Figure 1 (pathways B1 and B3). The same is true for physical activity (pathways C2 and C3). An important thing to note is that some of these factors work through obesity (pathways B2, C1, D1, D2, and D3), as well as independently affect disease. Diabetes is a critical example. One of the foremost researchers in the diabetes world summarized some of the major relationships in two broad articles on the topic. In each he showed how increases in weight could directly affect diabetes independent of the physical activity effects. He then went on to show independent physical activity pathways.4,5 Later we review further literature on the obesity-disease topics but these overviews by Zimmet et al.5 provide some sense of the vast literature underlying each relationship and how a selective use of literature could miss the whole picture of the pathway and lead to a distorted conclusion. There certainly are important issues raised by Campos et al.1—some of which need careful review and do lead to areas where further research is needed. However, in contrast to their four main claims, our position is clear that increase in obesity and its health consequences are real, and the scientific community needs to provide more responsible solutions to this serious public health concern, instead of nullifying existing scientific evidence based on discriminatory use and fallacious interpretation of literature. This article proceeds by discussing each of the points raised by Campos et al.1 It is asserted that the weight increases are modest. What is implied is that weight increases are occurring in a small proportion of the population and these changes are small. On the one hand, many of Campos et al.'s inferences to ‘insignificant’ weight change over time based on cross-sectional trend analyses at the population level reflect ecological fallacy.6 For example, their statement about the average American's weight gain explained by a few calories a day or a few minutes of walking could be very misleading, because average weight gain at the population level does not necessarily equate with weight gain at the individual level. The actual weight change of a population comprises a wide range of distributions. There may be a portion of the population who lose or do not change weight over time that would pull the mean weight change of the population down, which would make rather significant weight gains in some other groups of the population look trivial; ignoring these dynamics within a population may mask true changes that are happening among individuals. Also, what Campos et al.1 refer to as cessation of increase in weight based on the comparison of 1999–2000 and 2001–02 data is misleading, as it may simply be a reflection of sampling error, especially for population subgroups with relatively small sample size.7 In addition, what has been referred by Campos et al. as a subtle shift in BMI [body mass index or (weight in kilograms)/(height in meters)2] observed in the nationally representative data actually portends a remarkable increase in overweight/obesity. As the weight distribution shifts to the right, a greater proportion (the majority of people who belong to the centre of the distribution curve) of people enters into a higher range of BMI. Data from around the world show radical increases in obesity.8,9 We suggest looking at available data that can explain some of the real shifts to assess the global epidemic of obesity. We begin with the example of China, utilizing unique longitudinal data on Chinese adults (20–45 years old at baseline in 1989) from nine provinces.10 Our analysis shows that among adults, the weight change during the 11 year follow-up period (from 1989 to 2000) indeed has quite a wide distribution, and it is the majority of the people (73%) who gained weight (Figure 2). The average weight gain among those who gained weight during the follow-up period is 7.0 and 6.3 kg for men and women, respectively, uniformly across all baseline BMI categories. This is in contrast to Campos et al.'s first set of claims. Campos et al. in fact did not look at such longitudinal data to support their claims of a significant weight gain in only a minor portion of the people and people just crossing the ‘border’ to become classified as overweight and obese compared with a generation ago. Distribution of weight change between 1989 and 2000 (in kg) in Chinese adults aged 20–45 (n = 2739). Source: China health and nutrition surveys 1989 and 2000 This China example is important as it provides an example of the type of weight shifts we see in Mexico, many other South American countries, most Middle Eastern and South-east and East Asian countries.8 When we shift to higher income countries, there have been different types of shifts in the US and Russia and the few other more developed countries where overweight was very high. In these countries the increases in the past few decades are not as great in the normal weight category compared with the morbidly obesity categories. Among adults, in the US, the most profound is the large increase in the proportion of people with BMIs >35 and 40. Among US adolescents and children, however, the shifts have been across the BMI distribution and thus quite different from what has been observed among adults. Campos ignores these patterns.7,11,12 The recent two articles by CDC scholars—first Mokdad et al.13,14 cited death rates from obesity of 400 000 and then Flegal et al.15 showed 112 000 deaths—really created their own drama that most in the scholarly field dismissed. The death estimates from the first article were only partially adjusted for confounding factors. They also did not account for variation by age in the relation of body weight to mortality. The Flegal et al.15 study with its attribution of 112 000 deaths to obesity, while disputed for some questionable assumptions that might increase considerably the number of deaths, is well done and believable. What is important is that these are a lot of deaths but death probably does not describe the major health problems of obesity, which are morbidity, disability, hospitalization, and earlier entry to nursing homes. The quality of life is seriously compromised in obese individuals, but these health outcomes have only recently been measured and documented in depth. We discuss these issues later. Campos is correct to note that the relationships between levels of obesity and overweight are very complex and the final answer on these relationships is not very clear.16 Definition of optimal BMI may need to be continuously challenged based on comprehensive scientific evidence. At the same time, they are wrong in stating the studies of obesity and mortality should control for dietary and activity patterns—the very factors that cause obesity. Just as you should not control for diabetes (a mediator in this case, which is critical to the causal chain, and will attenuate the association of the exposure with the outcome if treated as a confounder) in trying to understand how obesity affects mortality, one must not control for the underlying determinants of energy imbalance and obesity. Also, Campos et al.'s comment ‘But the greatest problem with the statistical linkages between body mass and mortality is that other confounding factors are not considered, leaving little basis for drawing causal inferences’ shows poor understanding of epidemiological methods, as controlling multiple factors in analyses of observational studies does not convert non-experimental studies to experimental studies, from which only can we draw causal inferences.17 Literature supporting increased morbidity in obese individuals is quite overwhelming. Epidemiological studies have shown the links between obesity and adverse health outcomes, and physiological mechanisms are provided to support these relationships. Overweight persons face not only the full array of health problems noted in Figure 1 but they also retire earlier, go at younger ages into nursing homes, have higher absenteeism rates, and are more likely to be disabled. Below we briefly summarize some of the major obesity–morbidity relationships—direct effect of obesity on a chronic health condition and further links between the health condition to other health issues, if present. Hypertension: Increased blood pressure, as body weight increases, has been observed in both normotensive and hypertensive individuals. The pathogenesis of obesity-related hypertension is supported by the physiological mechanisms that leptin, free fatty acids, and insulin—whose levels are increased in obesity—may act individually and synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may act as amplifiers of the vasoconstrictor response. Increased renal tubular re-absorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, direct effect of insulin, hyperactivity of rennin-angiotensin system, and possibly by an alteration of intrarenal physical forces.18 Both obesity and hypertension predispose to cardiovascular morbidity and mortality.19 In turn, a history of hypertension is shown to increase the risk of type 2 diabetes independently of other known risk factors, including obesity.20 Elevated blood pressure is also a powerful risk factor for CHD and a significant predictor of mortality from stroke—for men and women.21 Dyslipidaemia [imbalance in total, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides]: Obesity has been associated with increased levels of triglycerides and decreased HDL-cholesterol, both of which are independent risk factors for cardiovascular disease.22 Elevated levels of total cholesterol, LDL-cholesterol, and triglycerides are major risk factors for CHD in both men and women,23 whereas HDL levels are correlated inversely with the risk of CHD.24 Insulin resistance (glucose intolerance, impaired glucose tolerance, hyperinsulinaemia): Insulin resistance has been strongly associated with overweight and obesity in many epidemiological studies.25 Hyperinsulinaemia, in turn, is believed to increase the risk of colon cancer by directly promoting colon carcinogenesis and stimulating insulin-like growth factor-I receptors.17,26,27 A similar mechanism is provided for the case of endometrial cancer.28 Cancers:Type 2 diabetes: It is well established that excess body fat leads to increasing insulin resistance, and insulin resistance predisposes to diabetes.22 Since obesity is characterized by a reduced number of insulin receptors and insulin resistance, the combination of epidemiological and metabolic data leaves little doubt that obesity is causally related to type 2 diabetes.32 Colon cancer: Higher BMI is associated with increased risk for colon cancer, with the association stronger for larger adenomas and for men. These may suggest an effect of factors related to adiposity on the promotion of cancer and a possible counteracting effect on these factors by oestrogens.29 Breast cancer: A contrasting pattern has been shown by menopausal status. Higher body weight, especially higher adult weight, is associated with increased breast cancer risk among post-menopausal women.29 Oesophagus cancer: An increased incidence of gastric reflux in persons with high BMI has been proposed as the underlying cause of more than a 2-fold increase in the risk of oesophageal cancer.29 Endometrium cancer: Convincing evidence from epidemiological studies shows a linear increase in the risk of endometrial cancer with increasing adult obesity.25,29 A hormonal mechanism is provided to support the association. Obese women have higher levels of serum oestrone and estradial, and decreased levels of sex hormone-binding globulin, both increasing the amount of bioavailable oestrogen. Elevated oestrogen levels stimulate endometrial epithelial cells, which is conducive to the development of cancer.30 Kidney cancer: Studies conducted across nations consistently show a more than 2-fold increase in renal-cell cancer risk among obese (both men and women), compared with those of normal weight.29 Increased levels of endogenous oestrogens in women may affect renal cell proliferation and growth by receptors present in renal cells or through paracrine growth factors.31 In turn, remarkable similarity of risk factors for type 2 diabetes and colon cancer, coupled with a general hypothesis that hyperinsulinaemia increases the risk of colon cancer, has led to a theory that type 2 diabetes itself, is a risk factor for colon cancer; this association has been observed in epidemiological studies.33 Diabetes is also a risk factor for CHD and CHD accounts for much of the serious morbidity and a high proportion of the premature deaths in type 2 diabetes.34 Diabetic men and women have a 2- to 3-fold and 3- to 7-fold increase in risk of CHD, respectively, compared with their non-diabetic counterparts.35,36 Coronary heart disease (CHD): Obesity has been shown to be an independent risk factor for CHD in both men and women.37,38 In addition, as described above, obesity increases the risk of hypertension, dyslipidaemia, and diabetes mellitus—all of which are risk factors for CHD. Stroke: BMI is a strong risk factor for total and ischaemic stroke. The pathway from obesity to stroke is thought of as being developed through hypertension, diabetes, and elevated cholesterol.39 Gallbladder disease: Epidemiological studies have reported an association between gall bladder disease, overweight, and obesity.22 The pathogenesis of gall bladder disease involves numerous mechanisms that are present in obese individuals, such as excess hepatic secretion of cholesterol and subsequent supersaturation of bile, increased gall bladder volume, and blunted gall bladder contractility.40 Osteoarthritis: Being overweight increases the amount of force across a weight-bearing joint.41 In addition, adipose may or growth factor that affect or underlying to obesity affects of and among the and et have the of to the life for individuals, free of and classified by weight status. was as walking on a level and walking and activities of in and of Among obese men and obese women years free of than normal weight or obese men and obese women years free of than normal weight These researchers however, to the higher mortality in the obese and overweight there was significant in the years with or between those overweight or obese and those with normal weight at research has been conducted the effect of obesity on the of The research has of in of or and from The majority of this work was conducted in and of these studies of have obesity to be associated with or One study and an increased BMI to be associated with study conducted in the US obesity to be associated with the outcome of in the or amount of or amount of and or amount of study obesity to be associated with in however, this association may on have the of obesity both in and public and the to be The major public and about of these the of obesity are not just by the obese individuals and their but a significant on We could go on to review other ways obesity affects an only but also but The key is to that these effects are and ignores a rather literature to a few to Campos et al.'s we evidence that weight is in a number of health and disease This with numerous epidemiological a causal between weight and health. a is shown to or in obese such as type 2 and There is a direct between what weight in diet and increased physical and health but literature also shows an independent effect of weight on and provides physiological mechanisms that support the effect of weight Campos et al.1 to see the whole related to more methods of weight are This certainly an on of overweight and obesity. we the shift in weight public health related to obesity that we are now will The fact that many countries in all of the world have that obesity and its with diabetes, heart disease, and stroke is utilizing and a major health to its population points to the of the Furthermore, it is clear that the by the vast increase in overweight and obesity and the health consequences of has increased articles on the topic. This is only Campos et al.1 are correct that there are many with direct financial interests involved in research and promotion activities related to the obesity On the one hand, there are by the all of issues such as portion or use of and in the among On the other the has a major role in major groups that to and related to obesity and from the have all dietary that from the US of The US does not have independent by the need to that such There are few major in for groups such as the for in the and a few in higher income countries who could be to be by from the or the As with many in the and obesity research has and from the to a range of studies in support of and the issues of to The for this but certainly has from many which might have his The and that of our from the public and can only be by what we and and how we are on such and how we are in trying to such The of might have to do with the the the other of all research from is much more to the and activity for many of the underlying of poor dietary and activity At the same time who are independent do not this way to that of is the cause of who the and who does not is a The has been most likely to physical activity and the of poor and for of Clearly this from but Campos et al. did not about such We do that physical activity patterns and dietary patterns have We how much of the increased energy from portion energy in the diet, and of these factors can we how much of the reduced energy from in activity at activity, and that the obesity increase is an and that increased weight and adiposity does not to poor health and is to the vast literature that shows the large increases in weight and BMI dynamics and also the important effects of these changes on global disease Campos et al. that by existing evidence of increasing obesity and its health they further the most subgroups in the it is the people with and some groups that from the obesity both adults and When the increases in weight nationally and are these and and will greater from obesity-related morbidity and mortality. We that a real health problem as is as the The is that obesity is by that are by the in which people our are not to the increasing weight will to and will obesity-related morbidity and mortality. to that will lead to obesity and related health problems is not what a should We the scientific community to in the to more responsible solutions for the obesity epidemic at the rather than the problem or being by number one is not necessarily public health. We the and and in for financial support to be to the We also to for for and for research of the has of interests of type with to this