Obesity is an independent risk factor for cardiovascular disease, type II diabetes, and certain forms of cancer. This statement is not even controversial. Ask virtually any board-certified physician, especially one who cares for patients with one of these health problems, and he or she will say, “Of course.”
However, there is a small movement today that attempts to claim that obesity itself is not a risk factor for any chronic illness. Instead, it is a lack of physical fitness that increases your risk for the above-mentioned diseases. This view is most likely the result of a lack of knowledge of the medical literature and an inability to understand how risk factors are gauged independently. Although the people who propose this view are well-meaning, the advice they give is medically quite dangerous. It is important, therefore, that someone attempt to clear up any confusion on the matter.
We know that obesity is an independent risk factor for the above-listed diseases simply by glancing at the medical literature. It is replete with studies that demonstrate this. For example, an in-depth review article on obesity appeared in the April, 2000 issue of the prestigious science journal Nature. In this review the author, Peter G. Kopelman, states, “Obesity causes or exacerbates many health problems, both independently and in association with other diseases. In particular, it is associated with the development of type 2 diabetes mellitus, coronary heart disease (CHD), an increased incidence of certain forms of cancer, respiratory complications (obstructive sleep apnoea) and osteoarthritis of large and small joints.”1
Let’s walk through the three basic types of diseases listed in the title of this article so that we can see exactly how obesity elevates the risk factors for each disease.
Cardiovascular disease (CVD)
Medical researchers became aware that obesity increases the risk of CVD through long-term studies that followed the medical histories of several people. The Framingham Heart Study, for example, followed 5,209 men and women over the course of 26 years. It showed that obesity was a significant predictor of CVD, particularly among women. It also showed that weight gain in the young adult years produced an increased risk for CVD in both men and women.2 While such data were valuable at the time, studies like these did have limitations, so more detailed studies were done to determine whether obesity itself was the cause of increased CVD risk, or whether it was some other factor that also was correlated to obesity.
Some of the most interesting studies that show obesity itself causes an increase in the risk of CVD come from examining the hearts of obese people. Studies showed that when a person’s weight increases, there is a corresponding increase in the total blood volume needed for circulation. This increased volume need is met mostly by increasing the amount of blood that flows into the heart for each beat rather than the total number of beats per second.3 In other words, the heart does not beat a lot faster to increase blood flow through the body as a person gains weight. Instead, it simply pumps more blood with each beat.
This presents a problem for the heart, especially the left ventricle. As the left ventricle changes to meet the added volume needs, its wall thickens. This hinders its ability to contract, and the amount by which it is hindered is proportional to the person’s obesity level.4-6 A more recent study shows that obesity produces the same problem in children.7
Now even though these direct heart studies show one way in which obesity directly affects the heart, more recent studies have shown that obesity attacks the heart in another way: Obesity produces an increased inflammation response in the body.8-10 A very recent study has shown that under the inflammatory conditions set by obesity, fat cells produce a bioactive molecule called C-reactive protein11. This molecule has been shown to be a powerful predictor of cardiovascular disease.12 Thus, we know that excess fat also attacks the heart by increasing inflammation in the body.
The confusion that can occur in a discussion of obesity and CVD relates to the fact that poor fitness also increases the risk of CVD13-15. Since poor fitness can often result in obesity, it is assumed by some that fitness is the overriding issue, and the association between CVD and obesity is, in reality, simply the association between poor fitness and CVD. This idea, however, does not stand up in light of the data.
First, the studies I have already mentioned clearly show that obesity itself has direct, negative effects on the heart. While fitness can mitigate some of these effects16, obesity causes them in the first place. Second, regardless of how fit a person is, if that person is obese, the excess fatty tissue will still increase inflammation in the body, thus increasing the risk of CVD.
This, of course, is born out in studies that compare the relative risks of low fitness and obesity in relation to CVD. For example, in a 1999 study, Wei and others compared CVD risk in men who were ALL fit, but some were normal weight, others were overweight, and others were obese. They showed that these fit men were 50% more likely to die of CVD if they were overweight and 60% more likely to die if they were obese as compared to the normal-weight fit men. In addition, they compared unfit men who were normal weight, overweight, and obese. In these unfit men, the ones who were overweight were 45% more likely to die of CVD, and the obese ones were 61% more likely to die of CVD as compared to those with normal weight. Of course, unfit men as a whole were significantly more likely to die of CVD than fit men. Thus, even though a lack of fitness is clearly a risk factor for CVD, once fitness is taken into account, obesity still plays a role. In fact, the authors conclude that a lack of fitness represented only 39% of the CVD risk in obese men. This is why the authors state, “Data presented in this article support the hypothesis that low cardiorespiratory fitness adds to overweight and obesity in influencing mortality adversely.”15. Note how they worded their statement. A lack of fitness adds to overweight and obesity. In other words, fitness and obesity are independent risk factors.
In a later study, Mercedes and others examined hypertension, diabetes, metabolic syndrome, and hypercholesterolemia in people. These conditions are all recognized risk factors for CVD. They showed that while fitness does reduce the risks of getting these CVD-related diseases, it is only part of the equation. As the authors note:
Cardiorespiratory fitness in young men and women, estimated by the duration of a maximal treadmill exercise test, was inversely associated with the risk of developing hypertension, diabetes, metabolic syndrome, and hypercholesterolemia in middle age. Our findings were only partly attributable to body mass and weight maintenance, suggesting that fitness plays an important independent protective role in the development of cardiovascular risk factors. However, among those who became obese earlier in life (possibly during childhood or adolescence), fitness does not protect against developing diabetes or metabolic syndrome.17
The authors conclude that part of the reduction in risk was the result of weight loss, and part was the result of fitness. Thus, fitness and obesity are independent risk factors for CVD. Also, notice that if the person became obese early in life, fitness did not reduce the risk of diabetes or metabolic syndrome.
In addition, a very thorough study in the European Heart Journal compared CVD hazard ratios among men and women. They grouped the men and women according to whether they were physically active or physically inactive as well as according to body mass index (BMI), one of the standard measures of obesity. Active women with high BMI (greater than or equal to 30) had a 56% higher CVD hazard ratio than active women with low BMI (less than 30). Active men with high BMI had a 35% higher CVD hazard ratio than active men with low BMI. Of course, the active men and women all had lower CVD hazard ratios than the inactive men and women. This, of course, tells us that obesity and physical inactivity are both independent risk factors for CVD. This is why the authors note, “In conclusion, our study confirmed that both physical inactivity and obesity are important risk factors for CVD.”18
Finally, in a very recent study, Demetra and others did extensive examinations on 135 healthy men and measured 18 established risk factors for CVD. They found that while body mass index, percent body fat, and waist circumference were consistently associated with all metabolic risk factors for CVD and many blood-related risk factors, fitness was associated with only some metabolic risk factors and NONE of the blood-related risk factors. Thus, fatness increased the risk of CVD more than a lack of fitness. This is why the authors state, “Body fatness is a better predictor of CVD risk factor profile than aerobic fitness in healthy men. Although habitual physical activity is an effective strategy for preventing CVD, elevated body fatness is associated with an adverse CVD risk factor profile independently of aerobic fitness.”19
As you can see, then, obesity is an independent risk factor for CVD. Physical fitness can reduce the hazards associated with obesity, but it cannot eliminate them. To be as healthy as possible from a cardiovascular viewpoint, you must be physically fit and not obese.
Diabetes
Obesity is an independent risk factor for type 2 diabetes as well. This is mostly through the action of insulin resistance. When a person is insulin resistant, his or her cells do not respond properly to the insulin being produced by the body, and as a result, the cells do not take in the proper amount of glucose. This leads to high glucose levels in the blood, which causes the body to produce even more insulin. This condition strongly predisposes a person to type 2 diabetes.
Researchers have known for a long time that increased weight increases the risk of type 2 diabetes20. However, they have also known that physical activity can reduce the risk of type 2 diabetes.21 Thus, once again, scientists needed to determine whether or not obesity and a lack of physical fitness are independent risk factors for the disease.
One study I have discussed already addresses this question. The study by Mercedes and others demonstrated that while physical fitness did play a role in determining the risk factor for diabetes, obesity also played an independent role. Furthermore, if a person became obese early in life, physical fitness did not reduce the person’s chance of developing type 2 diabetes17. This, of course, shows that physical fitness and obesity are independent risk factors for type 2 diabetes and, in fact, obesity seems to be the stronger of the two.
Two other studies agree with this general conclusion. Hu and others followed more than 80,000 nurses for 16 years and considered several factors such as BMI, smoking status, physical fitness, and diet. They showed that by far, the largest risk factor was obesity. The higher the BMI, the higher the risk of diabetes. They state, “Excess body fat is the single most important determinant of type 2 diabetes. Weight control would be the most effective way to reduce the risk of type 2 diabetes…”22 In addition, they say, “Our data suggest that the percentage of cases of diabetes that are preventable by diet and exercise independently of body weight is greater among women of normal weight than among obese women.”22 Thus, physical fitness does plays a role apart from obesity, but as the authors say, obesity is the much stronger risk factor. In addition, physical fitness does more for women of normal weight than it does for obese women.
Weinstein and others produced a study that reaches essentially the same conclusion. They showed that while the risk of type 2 diabetes depended on both the level of physical activity and BMI, the risk was correlated to BMI more strongly than to physical fitness. As the authors themselves note, “Although BMI and physical inactivity are independent predictors of incident diabetes, the magnitude of the association with BMI was greater than with physical activity in combined analyses. These findings underscore the critical importance of adiposity as a determinant of diabetes.”23 Note that “adiposity” is a term that refers to the amount of fat tissue in a person’s body.
Why is obesity such a strong risk factor for diabetes? It goes back to the inflammation issue I have already discussed. Several studies have shown that type 2 diabetes is associated with inflammation24. Other studies have now demonstrated that the chemicals partly responsible for inflammation can be produced by fat tissue in obese people. I have already discussed a few of these studies9-12, but I want to discuss two more now.
In a study of mice, Xu and others showed that insulin resistance is at least in part the result of the inflammation caused by obesity. They specifically looked at macrophages, which are white blood cells that are associated with the inflammation response. They analyzed the level of macrophages in white adipose tissue (WAT – a type of fat tissue) and related that to the insulin resistance in the mice. They state, “These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance. We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue.”25 Note that adipose tissue is fat tissue.
The correlation between inflammation and insulin resistance is not only found in mice. Festa and others studied more than 1,000 adults (age 40-69 years) and found that insulin resistance is strongly correlated with inflammation factors26, particularly C-reactive protein, which as I have already noted, is released by fat tissue.11 This is why they state, “We suggest that chronic subclinical inflammation is part of insulin resistance syndrome.”26 These data are supported by Aruna and others, who also demonstrate that the development of type 2 diabetes is correlated with C-reactive protein and another inflammation marker, IL-6.27
In the end, then, we see that obesity is also an independent risk factor for type 2 diabetes. In fact, while physical fitness does play a role, studies suggest that obesity’s role is stronger in raising the risk of type 2 diabetes than is a lack of physical exercise. This is well understood when one considers the intimate relationship between inflammation, insulin resistance, and type 2 diabetes.
Certain Cancers
Obesity is also an independent risk factor for certain cancers. For example, Goodman and others explored the relationship between diet, body size, physical activity, and the risk of endometrial cancer. They showed that the women in the highest category of BMI had a nearly 4-fold increase in their risk of endometrial cancer as compared to those who had the lowest BMI. They additionally showed that physical activity produced only a modest reduction in risk.28
Breast cancer is strongly associated with obesity, but the relationship is complex. Huang and others studied more than 95,000 women for up to 16 years. They found that the current BMI was associated with breast cancer in a very strange way. For premenopausal women, higher current BMI actually protected against breast cancer, while for postmenopausal women, it increased the risk of breast cancer only slightly. The largest effect was based on weight gain after the age of 18. Those who gained more than 20 kg after the age of 18 were almost twice as likely to develop breast cancer after menopause as those who did not gain the weight.29 This conclusion was restricted to women who had not taken postmenopausal hormones, and it was consistent with an earlier study that found essentially the same thing.30
While I could go through many more studies demonstrating that obesity is linked to certain forms of cancer, it is more convenient to sum the issue up using a recent study on obesity and the inflammation response. Church and others examined obese patients and measured their inflammation status using a marker known as the macrophage migration inhibition factor. They used that marker because, as they state, “Elevated macrophage migration inhibitory factor (MIF) has been implicated as a causal mechanism in a number of disease conditions including cardiovascular disease (CVD), diabetes, and cancer.”31 They found that the obese patients had elevated levels of MIF, and that those who lost weight through physical exercise and a weight management program attained significantly lower levels of MIF.31
As you can see, then, obesity is also an independent risk factor for certain types of cancer.
In Summary
As I stated initially, the idea that obesity is an independent risk factor for CVD, type 2 diabetes, and certain forms of cancer is not controversial. Virtually every organization that deals with these issues indicates this. The American Diabetes Association32, the Centers for Disease Control33, the National Institutes of Health34, the National Cancer Institute35, the Mayo Clinic36, the American Cancer Society37, and the American Academy of Pediatrics38 all state in very recent articles that obesity is a risk factor for these diseases.
By far, the most interesting organization to examine on this issue is the Cooper Institute. The Cooper Institute has been on the forefront of learning the benefits that physical fitness provides to a person’s health. It has received more money from the NIH for studying physical fitness than any other laboratory, and it is recognized as a world leader in assessing the relationship between physical fitness and disease prevention. Thus, if any institute were to be “slanted” towards physical fitness, it would be the Cooper Institute.
What does the Cooper Institute say about the relationship between physical fitness, obesity, and chronic illness? I sent an E-MAIL to Dr. Stephen W. Farrell, Director of Professional Education at the Cooper Institute to find out the Institute’s stand on this issue. Here is what he wrote back:
The Cooper Institute agrees that obesity is an important public health problem, and is a major independent risk factor for chronic disease. Our published research shows that the greatest risk of disease and death is found in obese individuals who have low levels of cardiovascular fitness (as measured by a maximal treadmill stress test). The risk of death and disease is significantly reduced in obese individuals who are able to attain a moderate to high level of cardiovascular fitness. However, the lowest risk of death and disease is seen in individuals with a normal body weight who also have a high level of cardiovascular fitness. We have concluded from these many studies that low cardiovascular fitness level is a stronger risk factor than body weight/obesity etc. However, we do not say that obesity is not a risk factor.39 (emphasis mine)
Note that while the Cooper Institute thinks that low cardiovascular fitness level is a stronger risk factor than obesity, it continues to admit that obesity, in an of itself, is an independent risk factor for chronic illness. Thus, even one of the most “pro-fitness” institutes involved in obesity-related research understands the negative effects of obesity on health.
In fact, this is the important issue to bring forth. The relative importance of physical fitness and obesity as risk factors for chronic illness is not well understood. Knowledgeable scientists can honestly disagree on which is more important. Most likely, it is disease dependent. My reading of the literature indicates that for type 2 diabetes, obesity is probably a stronger risk factor than low physical fitness. However, for CVD, it is probably the opposite. However, I can certainly understand someone disagreeing with me on the relative importance of each factor. At the same time, I do not see how it is possible for anyone with even a passing knowledge of the medical literature to claim that obesity is not a risk factor for chronic illness. The data are simply too clear on the point.
REFERENCES
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17. Mercedes R. Carnethon, PhD; Samuel S. Gidding, MD; Rodrigo Nehgme, MD; Stephen Sidney, MD, MPH; David R. Jacobs, Jr, PhD; Kiang Liu, PhD, Cardiorespiratory Fitness in Young Adulthood and the Development of Cardiovascular Disease Risk Factors, JAMA, 290:3092-3100 (2003). Return to Text
18. Gang Hua, Jaakko Tuomilehtoa, Karri Silventoinen, Nöel Barengoc, and Pekka Jousilahti, Joint effects of physical activity, body mass index, waist circumference and waist-to-hip ratio with the risk of cardiovascular disease among middle-aged Finnish men and women, European Heart Journal 25: 2212-2219 (2004). Return to Text
19. Demetra D. Christou, PhD; Christopher L. Gentile, MS; Christopher A. DeSouza, PhD; Douglas R. Seals, PhD; Phillip E. Gates, PhD, Fatness Is a Better Predictor of Cardiovascular Disease Risk Factor Profile Than Aerobic Fitness in Healthy Men , Circulation111:1904-1914 (2005). Return to Text
20. Colditz GA, Willett WC, Stampfer MJ, et al., Weight as a risk factor for clinical diabetes in women., Am J Epidemiol 132:501-513 (1990). Return to Text
21. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr., Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus, N Engl J Med. 325:147-152 (1991). Return to Text
22. Frank B. Hu, M.D., JoAnn E. Manson, M.D., Meir J. Stampfer, M.D., Graham Colditz, M.D., Simin Liu, M.D., Caren G. Solomon, M.D., and Walter C. Willett, M.D., Diet, Lifestyle, and the Risk of Type 2 Diabetes Mellitus in Women, N Engl J Med. 345:790-797 (2001) Return to Text
23. Amy R. Weinstein, MD, MPH; Howard D. Sesso, ScD, MPH; I. Min Lee, MBBS, ScD; Nancy R. Cook, ScD; JoAnn E. Manson, MD, DrPH; Julie E. Buring, ScD; J. Michael Gaziano, MD, MPH, Relationship of Physical Activity vs Body Mass Index With Type 2 Diabetes in Women, JAMA.292:1188-1194 (2004). Return to Text
24. An excellent review of several of these studies can be found here: Grimble, R.F., Inflammatory status and insulin resistance, Curr. Opin. Clin. Nutr. Metab. Care. 5:551-559 (2002). Return to Text
25. Haiyan Xu, Glenn T. Barnes, Qing Yang, Guo Tan, Daseng Yang, Chieh J. Chou, Jason Sole, Andrew Nichols, Jeffrey S. Ross, Louis A. Tartaglia and Hong Chen, Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance, J. Clin. Invest. 112:1821-1830 (2003). Return to Text
26. Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykkänen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD, Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome, Circulation 102:42 (2000). Return to Text
27. Aruna D. Pradhan, MD,MPH; JoAnn E. Manson, MD,DrPH; Nader Rifai, PhD; Julie E. Buring, ScD; Paul M. Ridker, MD,MPH, C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus, JAMA 286:327-334 (2001). Return to Text
28. Goodman MT, Hankin JH, Wilkens LR, Lyu LC, McDuffie K, Liu LQ, Kolonel LN., Diet, body size, physical activity, and the risk of endometrial cancer, Cancer Res. 57(22):5077-85 (1997) Return to Text
29. Huang Z, Hankinson SE, Colditz GA, Stampfer MJ, Hunter DJ, Manson JE, Hennekens CH, Rosner B, Speizer FE, Willett WC., Dual effects of weight and weight gain on breast cancer risk, JAMA 278:1407-11 (1997). Return to Text
30. Barnes-Josiah D, Potter JD, Sellers TA, Himes JH., Early body size and subsequent weight gain as predictors of breast cancer incidence (Iowa, United States), Cancer Causes Control 6:112-8 (1995). Return to Text
31. Church TS, Willis MS, Priest EL, Lamonte MJ, Earnest CP, Wilkinson WJ, Wilson DA, Giroir BP., Obesity, macrophage migration inhibitory factor, and weight loss, Int J Obes (Lond). 6:675-81 (2005). Return to Text
32. http://www.diabetes.org/weightloss-and-exercise/weightloss/getting-started.jsp Return to Text
33. http://www.cdc.gov/nccdphp/dnpa/obesity/ Return to Text
34. http://win.niddk.nih.gov/publications/health_risks.htm Return to Text
35. http://www.cancer.gov/directorscorner/directorsupdate-01-20-2004 Return to Text
36. http://www.mayoclinic.com/health/type-2-diabetes/DS00585
http://www.mayoclinic.com/health/heart-disease/HB00057 Return to Text
37. http://www.cancer.org/docroot/PED/content/PED_3_1x_Link_Between_Lifestyle_and_CancerMarch03.asp Return to Text
38. http://aappolicy.aappublications.org/cgi/content/full/pediatrics;112/2/424 Return to Text
39. E-MAIL communication from Dr. Stephen W. Farrell Return to Text