Posted on 11 May 2011 14:44
By Peter Janiszewski, Ph.D.
Originally published in Obesity Panacea, a PLOS Blog
This is a each part of a 5-part series delving into the fascinating and seemingly paradoxical research on people who despite being obese, remain metabolically-healthy.
Is Metabolically Healthy Obesity an Oxymoron?
To date, countless epidemiological studies have shown that as you move from a normal weight (BMI = 18.5-24.9 kg/m2) towards overweight (BMI = 25-29.9kg/m2) and obesity (BMI ≥ 30 kg/m2) the risk of many diseases increases exponentially.
Does this imply that every individual carrying excess weight is guaranteed to develop diabetes, cardiovascular disease, cancer, or some other disease?
Although this belief prevails, the cumulative research suggests the answer to the above question is a resounding “NO!”
It all started in 1965. Two researchers, Albrink and Meigs, were performing a general investigation into the health of factory workers, and noted a rather counter-intuitive result: that “many obese men had normal triglycerides.”
Subsequently, in 1982, Ethan Sims first included the designation of “healthy obese” subtype in his classification of obesity, thereby first identifying a unique subset of obese individuals that appear to be at least partially protected from the development of the metabolic disturbances generally attributed to obesity.
Today it is believed that approximately 25-30% of obese individuals remain metabolically healthy (normal blood glucose, blood lipids, blood pressure, and cytokine profile) despite their excess weight. However, despite awareness of the metabolically-health obese phenotype for close to 30 years, there currently exist no established criteria by which to define these individuals. Not surprisingly, there is significant variation in the predicted prevalence of these individuals within the total obese population.
Japanese Sumo Wrestler in 2010 Tournament
image by FourTildes
The defining characteristics of the metabolically healthy obese phenotype, in contrast to obese individuals with metabolic risk, include limited abdominal, particularly visceral fat accumulation, an earlier onset of obesity (<20 years) and high levels of physical activity. Additionally, black obese individuals have a greater tendency of being metabolically-healthy in contrast to white obese.
Japanese sumo wrestlers are often used as a popular example of metabolically healthy obese. They are morbidly obese and yet due to their high level of activity have very little visceral fat accumulation, tons of muscle mass, and a healthy metabolic profile – until they stop training, that is. Once they stop training, their fitness drops significantly, they accumulate excess fat in deleterious locations, and their metabolic profiles deteriorate. Football linemen are also a popular example of metabolically healthy obese, when they are training.
As a important caveat, there are countless other health issues brought on by carrying excess weight that are not always metabolic (i.e. joint problems due to excess load, skin infections, etc.). Thus, it is often argued that despite being metabolically-healthy these individuals may still be far from optimal health.
Nevertheless, it is important to note that excess weight alone doesn’t absolutely guarantee the presence of metabolic disease. There is certainly truth to the notion that there is more to health than the number on one’s bathroom scale. 1,1
Prospective Risk of Disease
The cross-sectional research certainly supports the existence of a sub-population of metabolically-health obese individuals; approximately 1 in 3 obese individuals has a healthy metabolic profile. But what about the chances of developing chronic diseases such as diabetes or cardiovascular disease – two common ailments tied to carrying excess weight?
We will look at two separate studies investigating this question.
In the first study, 2902 men and women were subdivided into different groups based on their weight (normal, overweight, and obese) and metabolic status (presence or absence of metabolic syndrome or insulin resistance). While this subdivision is a tad confusing, keep in mind that people with excess weight but lacking the presence of the metabolic syndrome or insulin resistance would be considered to fit the definition of the metabolically-healthy obese.
These individuals were prospectively followed for up to 11 years to see who would develop type-2 diabetes or cardiovascular disease.
And what say the results?
Over the follow-up period, 141 subjects (~5% of population) developed type-2 diabetes, and 252 experienced their first cardiovascular event (~9% of population).
In terms of risk for developing cardiovascular disease, overweight or obese subjects without the metabolic syndrome or insulin resistance, that is, metabolically healthy obese, were at NO higher risk in comparison to their equally healthy, but normal weight individuals.
Similar story in terms of type-2 diabetes risk; overweight or obese subjects without metabolic syndrome and overweight, insulin-sensitive subjects were not at increased risk for diabetes in comparison to healthy, normal weight individuals.
The authors of this study provide the following conclusion [emphasis added]:
“[…] in the absence of metabolic abnormalities, obesity itself did not increase risk for cardiovascular disease and was a relatively weak risk factor for incident diabetes.”
A similar conclusion was reached by Canadian researchers following a group of 1824 healthy men for a duration of 13 years.
Again, the subjects in this study were divided into 3 categories of body weight (normal weight, overweight, and obesity) and also on the presence of the metabolic syndrome.
During the follow-up period, 284 of the men developed cardiovascular disease.
Once again, the obese men who despite their excess weight had a relatively healthy metabolic profile (metabolically healthy obese) did not show any greater risk for developing cardiovascular disease in comparison to healthy, lean men.
The authors of this study, concluded the following:
“The results of this prospective population-based study indicate that the risk of ischemic heart disease associated with a high body mass index depended entirely on whether features of insulin resistance syndrome were simultaneously present.”
So, not only may 1 in 3 obese individuals have a healthy metabolic profile, but, in fact, their future risk of developing diabetes and cardiovascular disease may be equal to that of healthy, lean individuals.
But is there more to health than the level of triglycerides in one’s blood, or their risk of diabetes or cardiovascular disease? And if we consider other, potentially more telling outcomes – such as mortality – will metabolically-healthy obese individuals still be considered healthy?2,2
Obese, but Metabolically Healthy: Lower Risk of Mortality?
We just found out that out that diabetes and cardiovascular disease risk among metabolically healthy obese individuals is no greater than that of healthy lean individuals. Therefore, I pose the following question:
Is there more to health than the level of triglycerides in one’s blood, or their risk of diabetes or cardiovascular disease? And if we consider other, potentially more telling outcomes – such as mortality – will metabolically-healthy obese individuals still be considered healthy?
This question brings us to today’s post in which we discuss a landmark study published in the journal Diabetes Care, which was conducted by friends and colleagues of ours: Dr. Jennifer Kuk and Dr. Christopher Ardern. But rather than personally writing about the study, I figured I’d interview Dr. Kuk and get the details of their findings directly from the primary author.
OP: If you were to sum up the main findings of your study to a non-scientist at a dinner party, what would you say?
Dr. Kuk: I’d say that “My study shows that individuals who are obese and do not have common diabetes and heart disease risk factors die at the same rate as those who do. This means being overweight alone puts you at higher risk for dying, even though you do not high blood pressure, high cholesterol or high blood sugar. This highlights the negative health impact of body weight alone”.
OP: Why do you think the prevalence of metabolically-healthy obesity in your study was so much lower than previously reported in others (6% vs 20-30%)?
Dr. Kuk: The prevalence was lower in our study as compared to others simply because we used a more strict definition of metabolically normal. Other studies used insulin resistance or the metabolic syndrome (3+ risk factors) alone, but we defined ‘metabolically healthy’ as the absence of insulin resistance or any metabolic syndrome criteria. We felt this would be a more accurate definition of ‘metabolically healthy’ as each of the metabolic syndrome criteria are associated with morbidity and mortality alone.
OP: How do you reconcile the findings from the current study with those of prior studies suggesting that metabolically-health obese individuals are at no greater risk for developing type-2 diabetes or cardiovascular disease than normal weight individuals?
Dr. Kuk: Although I don’t know which studies you are referring to exactly, but in our study, 80% of the deaths in the metabolically-healthy obese were due to cancer and ‘other’ causes. Other causes are likely traumatic injuries, which highlights an important point. Obese individuals are less likely to survive a trauma as compared to normal weight individuals despite similar injuries. This is related to longer transport times due to their higher body weight, and difficulty assessing and treating the injuries due to their increased size. Further, they are less likely to see their physicians regularly, which may be in part why cancer is generally diagnosed in obese individuals at later stages. Thus, this study fits in line with the idea that these individuals are not more likely to develop these metabolic diseases, but still die from other causes.
OP: Recently, Drs. Sharma and Kushner proposed a new staging system for obesity treatment suggesting that obese individuals without established metabolic risk should be counseled to maintain current weight, rather than lose weight (Read about this on Dr. Sharma’s Obesity Notes blog). Do the results of your study agree or disagree with these recommendations?
Dr. Kuk: One can examine this question from a theoretical or practical standpoint. From a theoretical stand, weight loss improves metabolic factors, functionality and several psychological and social factors, and thus it would be intuitive to recommend that all obese lose weight. However, from a practical perspective it may be unethical to recommend an individual who is not presenting with overt disease to try to lose weight as most individuals fail to maintain their weight loss over the long term. Repeatedly failed attempts to maintain weight loss has been shown to elevate one’s risk for diabetes, cardiovascular and cancer for a given BMI. In other words, it may be better to recommend maintenance of weight rather than prescribing weight loss, knowing that they are likely to fail and be worse off because of it. Though we did not examine this issue, Sharma and Kushner’s staging system examines non-metabolic consequences as well, and it is reasonable to assume that these are equally important to examine as they are also important aspects of health, and inclusions of these factors may alter the associations observed.
OP: Are metabolically-healthy obese individuals actually healthy?
Dr. Kuk: I think that whether metabolically-healthy obese are actually healthy is dependent upon the accuracy of the definition. As we see that obese without cardiovascular disease or diabetes risk factors are at elevated cancer risk implies that our definition of metabolically healthy is not capturing cancer metabolic risk factors. Similarly, risk for trauma events may also reflect aspects of health that may or may not be captured by metabolic risk factors, but are crucial aspects of health. For example, musculoskeletal fitness would be a predictor of risk of falling or functionality.
Thus, if we used a more encompassing definition, we would likely see that these metabolically-healthy obese may be at lower risk for mortality and are healthy. However, as our definition only identified 6% metabolically healthy obese, I would suspect that an all encompassing definition for healthy obese would be a very minuscule proportion of the population.
OP: Thanks very much Dr. Kuk!
So, despite a healthy metabolic profile, no greater risk of diabetes or cardiovascular disease, metabolically-health obese individuals may still be at greater risk of dying early.
Maybe, they’re not so healthy after all.
This work would certainly suggest that all obese individuals – even those with a healthy metabolic profile – should attempt to lose weight. But what if losing weight actually makes these, otherwise healthy, but obese individuals less healthy? 2,3
Obese, but metabolically healthy: Is weight loss detrimental?
While countless epidemiological studies have shown that as you move from a normal weight (BMI = 18.5-24.9 kg/m2) towards overweight (BMI = 25-29.9kg/m2) and obesity (BMI ≥ 30kg/m2) the risk of many diseases increases exponentially, it is also true that approximately 25% of obese individuals are metabolically healthy despite their excess weight. These individuals are also at no greater risk of chronic diseases such as diabetes and cardiovascular disease than their lean counterparts. However, as we learned yesterday, despite being metabolically-healthy obese individuals may still be at greater risk of mortality.
This latter point would indicate that despite suggestions to the contrary, all obese individuals, regardless of their metabolic status should be counseled to lose some weight.
But should they? What if weight-loss among otherwise healthy obese individuals actually makes them unhealthy?
According to a paradoxical study by Karelis and colleagues, otherwise healthy obese women who lose weight via dieting may actually WORSEN their metabolic profile.
In the study, a sample of obese women were divided into either metabolically healthy (20 women) or metabolically at-risk (24 women) based on their level of insulin sensitivity (a marker of diabetes risk – the more insulin sensitive, the better) as measured using the euglycemic-hyperinsulinemic clamp procedure. These women then underwent 6 months of a medically supervised dietary weight loss program consisting of approximately 500-800 calorie reduction in daily food intake.
After the intervention all women lost a significant amount of body weight (approximately 6-7%).
More interestingly, however, while the metabolically at-risk obese women showed a 26% increase in their level of insulin sensitivity, the insulin sensitivity of the metabolically healthy obese women actually deteriorated by 13%!
In other words, by losing weight those obese women who were originally metabolically healthy may have actually increased their risk of diabetes.
This finding is very unexpected, and as of yet has not been corroborated by another study. Nevertheless, it does raise the very intriguing possibility that weight-loss among otherwise healthy obese women may not only unnecessary but, in fact, counter-productive.
This finding falls broadly in line with a recommendation paper by Drs. Arya Sharma and Robert Kushner published in the International Journal of Obesity earlier this year. In that paper the authors proposed a novel obesity classification system which not only assesses weight, but also health complications of excess weight. Germane to the above discussion, Sharma and Kushner recommend that among obese individuals who have “no apparent obesity-related risk-factors” the goal of patient management should be to simply avoid further weight gain, or maintain current weight, rather than to induce weight loss. (To read Dr. Sharma’s full discussion of the new classification system please visit his blog here.)
In essence, the idea that healthy obese individuals may not have much to benefit from weight loss, metabolically speaking, is not that surprising – they are healthy to begin with! However, whether weight-loss may actually be ill-advised for healthy obese individuals needs to be investigated by future studies – until a counter-intuitive finding such as this one is corroborated, many remain doubtful (including me). For example, it remains unknown whether exercise-induced weight loss among healthy obese individuals could also result in metabolic detriment (doubtful). Additionally, we have currently no idea if the above finding also holds true among men. 4,4
Obese, but Metabolically Healthy: Is Weight Loss Beneficial?
So what have we learned thus far?
1. About a third of obese individuals fail to exhibit the metabolic complications commonly attributed to excess weight.
2. These same individuals also seem to be at the same relative risk of diabetes and cardiovascular disease as equally healthy, but lean individuals.
3. Nevertheless, despite being metabolically healthy, some evidence suggests that excess weight may put such obese individuals at risk for early mortality due to other, non-metabolic, factors.
4. This latter point would imply that all obese individuals should be encouraged to lose weight, despite their metabolic health. This, in fact, is in line with guidelines developed by leading health authorities which currently recommend weight reduction as the primary treatment strategy for all obese patients, regardless of metabolic health. However, as we learned yesterday, weight loss via caloric restriction among metabolically healthy obese may actually result in a deterioration in insulin sensitivity, thereby increasing risk of developing type-2 diabetes.
Now, as most of you know, when a completely counter-intuitive finding like this comes along, where even the study authors fail to come up with a plausible mechanism, it is up to other researchers to follow up with additional research to either corroborate or refute this original finding.
Because I am personally drawn to paradoxical and counterintuitive findings in science, I was very intrigued by the findings of Karelis and colleagues and decided to follow up their study, but include a few variations:
a) Since the study of Karelis et al. only used female subjects, we wanted to ensure this wasn’t due to a gender effect and thus included both men and women.
b) Additionally, to test the possibility that their finding was driven only by modality of weight loss (caloric restriction, in their case) we employed a number of weight loss interventions (diet alone, exercise alone, and the combination of diet and exercise).
c) Finally, while the original study only looked at insulin sensitivity, we decided to assess changes in other variables of interest (body composition, blood lipids, glucose and insulin levels, etc.).
In our study, which has just been published in the prestigious journal, Diabetes Care, a total of 63 metabolically-healthy obese men and women and 43 metabolically-unhealthy obese men and women participated in 3-6 months of exercise and/or diet weight-loss intervention.
And what did we find?
First, body weight, waist circumference, and total and abdominal fat mass were significantly reduced in all subjects – regardless of gender, modality of weight loss, and metabolic status.
Second, in contrast to the findings of Karelis et al., insulin sensitivity IMPROVED after weight loss in both the metabolically-healthy (by about 20%) and metabolically-unhealthy obese individuals. However, the improvement was greater in the metabolically-unhealthy subjects. See figure below.
Importantly, this improvement was similar across all weight loss modalities. In other words, dietary caloric restriction did not have a unique negative effect on insulin sensitivity.
Finally, while the metabolically-unhealthy obese individuals also showed improvement in numerous other outcomes (triglycerides, fasting glucose and insulin, HDL-cholesterol, and total cholesterol), a reduction in fasting insulin was the only other metabolic improvement among the metabolically-healthy obese. This latter finding is not surprising given the normal baseline levels of most metabolic risk factors among metabolically-healthy obese individuals. That is, since they were healthy to begin with – they can only get so much healthier after weight loss (ceiling effect).
Thus, we found no evidence of deterioration in metabolic profile among metabolically-obese individuals who lost weight via a lifestyle intervention.
While limited health care resources dictate the need to prioritize high-risk obese individuals for aggressive treatment, to imply that obese individuals who are metabolically healthy should not lose weight may not be the most appropriate public health message. Such a public health message may be particularly misguided at a time when the prevalence of obesity continues to increase, despite a greater public awareness of the benefits of weight loss. In this context, our findings reinforce current recommendations which suggest that all obese individuals should be encouraged to lose 5-10% body weight.
Although a fair number of obese individuals may have a perfect metabolic profile, it appears they may still experience negative consequences of their excess weight. Furthermore, weight loss achieved via lifestyle intervention appears to still bring about some metabolic benefit among previously healthy obese individuals (it certainly doesn’t seem to harm health). Given the numerous non-metabolic benefits of weight loss (mobility, joint problems, psychological status, sexual function, etc.), all obese individuals have something to gain from a modest 5-10% weight loss. 5,5
Peter Janiszewski has a PhD in clinical exercise physiology. He's a medical writer/editor, a published obesity researcher, university lecturer, and an advocate of new media in scientific knowledge translation. You can connect with Peter on Twitter. For more information please visit his website.
Published under a Creative Commons Attribution License (CCAL) from the The Public Library of Science (PLoS). Only minimal changes have been made to the original articles in order to fit this format. The author's original intentions or the meaning of the articles have been in no way affected by these slight changes.
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