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C. deFilippi. A Novel Technology for Measuring Cumulative Cardiac Biomarker Exposure over Time: What Happened When We Weren't Looking? Clin Chem 2012; 58: 25-27.


Christopher deFilippi is an Associate Professor of Medicine at the University of Maryland School of Medicine and Cardiologist at the Maryland Heart Center.


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Bob Barrett:
This is a podcast from Clinical Chemistry. I am Bob Barrett.

The prevalence of obesity is increasing at an alarming rate and with it the occurrence of cardiovascular disease, Type 2 diabetes, stroke, and certain types of cancer. Approximately, one third of adults in the US population are currently classified as obese. Globally, over 400 million adults are classified as obese, a number that is expected to double in just three years. Consequently, obesity and its associated health problems are placing a large burden on healthcare systems with the worldwide costs estimated to be between 0.7% and 2.8% of total healthcare expenditures. In addition, medical costs for obese individuals are substantially higher than for non-obese people. In the June 2012 issue of Clinical Chemistry, Dr. Jennifer Shea, from the Mount Sinai hospital in Toronto, Canada interviewed several in the laboratory medicine field seeking a consensus on how to deal with growing issue. Dr. Shea is our guest in this podcast.

Doctor, obesity has gone under a lot of media attention over the past 10 plus years due to increasing prevalence at an alarming rate, why do you think obesity rates keep increasing?

Jennifer Shea:
Well Bob, I think obesity is the consequence of the complex interplay between both the environment and our genetic background and both of these can influence, both our energy intake and our energy expenditure and when you get an imbalance and that can lead to what’s called the positive energy balance, or in other words an energy surplus. So when we have surplus of calories and that will ultimately result in obesity.

So now there are numerous factors that we know of that play a role in the sort of positive energy balance or energy surplus and these include obviously the availability or the increasing availability of energy-dense foods, our increasing sedentary lifestyle, so a decrease in physical activity, high stress levels, lack of sleep and even just a structure of our neighborhood. So some studies have shown that the incidence of obesity is smaller in some urban centers, whereas at the neighborhoods are set up in more of a grid like pattern, just because this facilitates walking, so we are increasing our energy expenditure.

Now in other urban areas, where there might be large number of freeways, or it’s not as easy to walk, as well in as in some ruler communities where this is the case, obesity rates are in fact typically higher. So when you compound all that information with the fact that our body actually has this innate ability to defend its body weight, and you can end up with the obesity epidemic, such as we are faced with today.

So what I mean by that is that under conditions that promote a negative energy balance, such as dieting or working out, increasing your physical activity levels, but our body in fact undergoes a complex set of responses that actually promote weight regain, so back to that homeostatic set point of our weight.

So as a result, treatment of obesity, keeping all of this in mind needs to follow guidelines for chronic disease management to prevent this weight regain. So studies are showing that yes we can be successful in weight loss, but it’s that weight loss management of keeping that weight down over time that we unfortunately haven't been that successful yet and that is certainly contributing to the increasing obesity rates.

Bob Barrett:
What are some of the comorbidities associated with obesity?

Jennifer Shea:
So I think this is something that we are all fairly familiar with and there are numerous comorbidities associated with obesity. Some of the more common ones include Type 2 diabetes; cardiovascular disease and this include obviously hypertension, stroke, dyslipidemia, as well as some certain types of cancer. So as the rates of obesity increased, we are obviously also seeing increases in the rate of all of these deceases as well. And an example of that would be that the rates of Type 2 diabetes which have increased substantially in the last 10 to 15 years and are also now reaching alarming proportion, as well as obesity.

And I think it’s important to be aware of these, because this is placing a huge burden on our healthcare system and will continue to do so in the coming years.

Bob Barrett:
Now are all obese people at risk for developing these conditions?

Jennifer Shea:
So that’s in fact actually a really interesting question and with some of the focus of my PhD work and I think it’s a very important one to address. Until recently it was actually thought that obesity was associated with this sort of uniform risk for all of those diseases that I just mentioned or comorbidities, so that if you are obese, your risk goes X% to develop Type 2 diabetes or cardiovascular disease.

However, recent work that's been done; I see in the last five years or so has shown that the decease risks associated with obesity are actually not in fact uniform. For example,

there are some individuals who despite having excess weight or being clinically obese, actually have a healthy metabolic profile, so when they are screened in their doctors office and their BMI puts them into the obese range or they have an elevated percent body fat or an elevated waist circumference, their fasting glucose and their lipids and their CRP maybe well within the reference interval for what we would expect in a healthy population or in a normal weight population.

So in the literature these people are termed metabolically healthy, but obese. So now in contrast to that, some individuals were classified as normal weight, again according to their BMI or their waist circumference or percent body fat, have a metabolic profile similar to what we would typically expect to see in obese individuals. So they may have an elevated fasting glucose, perhaps increased triglyceride levels, a decreased HDL cholesterol and they maybe hypertensive and have increased high sensitivity CRP.

So what we have sort of call these individuals in the literature is metabolically obese but normal weight, and they are obviously at an increased risk for all of the obesity associated comorbidities that I described in the previous question. So what I think is the important point to make is that the prevalence of the subtype of obesity is actually quite large. So, for example, some studies have demonstrated that the prevalence of metabolically healthy but obese individuals, is somewhere in the ballpark of 30% to 50%, and likewise, the prevalence of metabolically obese but normal weight individuals is approximately 25% give or take.

So judging from this in my opinion identifying these subsets of obesity and understanding them, coming to a better understanding of them will become an important task going forward.

Bob Barrett:
What sort of implications do you think this has from a public health perspective?

Jennifer Shea:
Well I think a realization of these subtypes of obesity exists will have major implication from a public health perspective. So for example, if physicians are screening individuals at risk for obesity and its associated comorbidities based on something like BMI or waist circumference, which is typically how it's done now in a doctor’s office, they may miss out on identifying metabolically obese, but normal weight individuals.

Obviously these patients wouldn’t -- not necessarily have an elevated BMI or not have a waist circumference about the cut point. So as the result of this, we maybe missing out on the opportunity to intervene at an early stage with these individuals, prior to them presenting with Type 2 diabetes or hypertension or it’s something like that, and we could intervene at an earlier stage, we might be able to prevent future disease by either implementing dietary strategies or giving them some sort of guidance in terms of increasing their physical activity levels, and hopefully bringing them metabolic profile into a more healthy range.

So it’s my belief that we need to increase certainly, increase awareness of these obesity subtypes in order to improve obesity management and hopefully combat this disease.

Bob Barrett:
Doctor what's known so far regarding the genetics of obesity and how many genetic polymorphisms are thought to be associated with obesity at this time?

Jennifer Shea:
Now there has been a lot of work done in this area. It started probably back in the early `90s. There were series of twin studies performed actually by a group here in Canada and they demonstrated that the heritability of obesity is extremely high, higher than blood pressure, higher than cholesterol levels and some of these other metabolic abnormalities that we are used to seeing.

In terms of the genetic etiology of monogenic forms of obesity, these have been well mapped out, something that I am sure, all of our listeners are familiar with, will be mutations in genes involved in appetite regulation, such as the leptin gene, the leptin receptor gene, but these forms of obesity are in fact quite rare, extremely rare actually. And the common form of obesity that I've been speaking of is a complex disease as I mentioned and it involves the action of many gene that play out on the environment that we live in.

According to the latest Obesity Gene Map, which was published a number of years ago; I think the latest one was published in 2006, that was over 600 polymorphisms that are associated with common obesity in either humans or animal models.

I’d said that the current estimate would probably be even greater than a thousand. Now genome-wide association studies or GWAS have been quite successful in identifying a number of genetic variations, probably the most robust association has been with the fat mass and obesity associated gene or FTO and this does show the great correlation with common obesity to-date.

And the important thing with polymorphisms within this gene is that this has been replicated across a number of different cohorts, across a number of different populations, unfortunately, the polymorphisms within this gene can only explain approximately 1% of the heritability of BMI. So there is obviously still a lot left to do, a lot of work left to uncover, a lot variations of polymorphisms left to decipher regarding the genetic etiology of this disease.

Bob Barrett:
Do you think the general public should be screened for these genetic polymorphisms?

Jennifer Shea:
I don’t believe that the general population should be screened at this time, so although the GWAS have been successful in identifying a number of variations associated with obesity, in terms of our understanding of the physiology surrounding these genes in the polymorphisms within them, this remains basic at best.

So we also need to understand how these polymorphisms interact with the relevant environmental factors and other things before I think global screening is undertaken.

So in terms of I guess what my hope would be going forward would be that screening for these polymorphisms will eventually be part of the assessment for obesity risk, but at the current time we aren’t quite there yet.

Bob Barrett:
Well finally Dr. Shea, let’s look ahead. What do you think will be the most important area to focus on in regard to future obesity research?

Jennifer Shea:
Well, I think future research needs to focus on all of the aspects that I've touched on today, and particularly I think it will become more important again to increase our understanding of the etiology of the different subtypes of obesity, especially those two that I spoke off. So in this regard, I think that it will become very important to understand the genetic differences between these subtypes as this may lead to the identification of novel obesity candidate genes that haven’t been identified yet, and perhaps that will have an even greater effect size. And once we have a more complete understanding of all of the physiological causes of obesity, hopefully, we'll be able to come up with better treatments as well as prevention strategies that will result in combating this disease, and that’s the ultimate goal.

Bob Barrett:
Dr. Jennifer Shea is from the Mount Sinai Hospital in Toronto. She has been our guest in this podcast from Clinical Chemistry. I'm Bob Barrett. Thanks for listening!