While researching the material for the June 11 2010 article on obesity, I ran across the recent work of Katherine M. Flegal and her colleagues at the National Center for Health Statistics of the Centers for Disease Control and Prevention (CDC). Dr. Flegal has long been a leading obesity epidemiologist, and led the research that first identified the increased prevalence of obesity in the United States beginning in the 1980s.
Dr. Flegal’s recent work has been based in large part on the most recent data from the National Health and Nutrition Examination Survey (NHANES), and on long-term data from NHANES between 1960 and the early 2000s. In 2005, she and her colleagues published a report in the Journal of the American Medical Association (JAMA) on mortality as a function of Federally-defined weight class–underweight, normal weight, overweight, and obese. These categories were determined on the basis of the body mass index (BMI), with underweight at <18.5, normal weight at 18.5-24.9, overweight at 25-29.9, and obesity at >30. Subsequently, in 2007, Dr. Flegal and her colleagues published a report in the JAMA analyzing excess deaths in the underweight, overweight, and obese classes by cause (e.g., cardiovascular disease, diabetes, cancer, etc.).
Dr. Flegal has published other reports relevant to her analyses in these two papers between 2005 and 2010, and has lectured widely on her findings. Her research was also discussed in a New York Times article in 2005, a 2007 article in the British newspaper The Independent, and in a January 2010 interview in the Association for Psychological Science Observer.
The surprising conclusion of Dr. Flegal’s research is that people in the overweight class have a lower risk of death than those in either the normal weight or the obese class. According to the 2005 study, obesity is associated with about 112,000 excess deaths per year (with most deaths [about 82,000 deaths] concentrated in the extreme obesity class, BMI >35), and underweight is associated with about 26,000 excess deaths per year, but overweight is associated with preventing 86,000 excess deaths per year. (“Excess deaths” refers to the number of deaths per year as compared to the normal weight class).
According to the 2007 study, underweight was associated with significantly increased mortality due to noncancer, non-cardiovascular disease (CVD) causes, but obesity was associated with associated with significantly increased mortality due to obesity-associated cancers, CVD, diabetes, and kidney disease. Thus excess deaths in the underweight and the obese classes vary by cause. Overweight was not associated with either increased or decreased deaths due to CVD, and overweight was not associated with excess deaths due to obesity-associated cancers. However, overweight was associated with a significantly reduced number of excess deaths due to noncancer, non-CVD causes.
Dr. Flegal and her colleagues found that the association of mortality with BMI appears to be much weaker in the most recent surveys as compared to earlier ones. In the most recent data, the association of overweight and mild obesity with risk of death appears to be weak and not statistically significant. This suggests that the association between mortality and weight has been decreasing with time, perhaps due to improvements in medical treatments and in public health. The results of other researchers confirm this hypothesis, and indicate that better management of the risk of death from CVD (e..g, the use of preventive measures such as blood pressure medications and statins, as well as better management of heart attacks via such procedures as angioplasty and stent placement) is responsible for the decreasing risk of obesity-associated death.
The other interesting issue is the risk of weight-related mortality and age. The association of mortality with weight decreases in older people, especially for those over 70, with the overweight group again having a lower risk of death than the underweight and the obese. Since most people die when they are over 70, this may account, at least in part, for the reduced risk of death in the overweight group in Dr. Flegal’s studies.
Dr. Flegal’s analysis of population weight data over time leads her to dispute the term “obesity epidemic” that most researchers and commentators in the field (including me) have been using. The prevalence of obesity had been stable between 1960 and 1980, but then increased markedly between 1980 and 2000. This increase is what has been referred to as an “epidemic”, since it was expected to continue. However, the increase in prevalence of obesity appears to have diminished since 2000. Moreover, limited data going back to the Civil War suggests that weight in the American population has been increasing since that time, and increasing at a slower rate in recent decades than in the latter half of the 19th century. Dr. Flegal therefore sees obesity as endemic, rather than epidemic.
As might be expected, Dr. Flegal’s conclusions have generated a lot of controversy. Many researchers do not believe the findings, in some cases on the basis of their own earlier studies. Others are simply reluctant to go against the received wisdom that excess weight is a major health hazard, and perhaps the biggest public health problem facing the United States and many other countries. Many researchers note that Dr. Flegal’s studies measure only mortality, not the incidence of such diseases as diabetes and CVD. This is a valid criticism, calling for more epidemiological research. However, many epidemiologists note that Dr. Flegal’s methodology and data are solid, and that she and her colleagues are well respected in their field.
Dr. Flegal’s studies indicate that the designation of obesity and overweight as America’s biggest health problem, and the main cause cause of the rise in health care costs–as discussed in our June 11 2010 blog post–may be overblown. The emphasis for most overweight and moderately obese people may need to be exercise and diets that promote health, whether patients lose weight or not. Given the difficult that most overweight or obese people have in losing weight and keeping it off over the long term, this may be a more realistic approach.
What is a “diet that promotes health”? What is considered “healthy” changes over time, as the result of new research as well as other factors. It is not the purpose of this blog to prescribe or discuss different diets. There are many, many blogs–not to mention books, television programs and other media–that do that. A good place to start, however, might be the work of Walter Willett. (Dr. Willett has disputed the findings of Dr. Flegal’s research, which indicates the level of complexity and disagreement in the obesity field.) Diet and exercise issues should of course be discussed with one’s doctor, but informed patients will usually get better results than uninformed ones.
For those of us in the pharmaceutical and biotechnology industry, the controversies about weight and diet affect the enterprise of drug discovery and development, especially in the metabolic disease and CVD fields. Drugs for such conditions as diabetes and dyslipidemia, as well as antiobesity drugs, are indicated as “adjuncts to diet” or “adjuncts to diet and exercise”. Clinical studies do indicate that these drugs work best when combined with diet and exercise. However, which diet and exercise regimens might be best for various groups of patients, and which diet and exercise regimens might best potentate the efficacy of a drug for various groups of patients, is called into question by the results of Dr. Flegal’s research and the debate over them in the obesity research community. And if weight-associated mortally has been decreasing with time due to improvements in medical treatments, we need to keep up the good work, and develop improved treatments and preventives for such diseases as diabetes and its complications, and for CVD. (It is the complications of diabetes that are responsible for the greatest level of mortality and disability due to diabetes, as well as the bulk of diabetes-related health care costs.) These new drugs should address unmet medical needs in the metabolic disease and CVD fields.
Health care policy makers should also stop blaming the overweight and the obese and their “lack of personal responsibility” for the woes of the health care system. As we discussed in our June 11 article, this is true whether Dr. Flegal’s conclusions are valid or not.