Scott M. Grundy on Bringing Metabolic Syndrome to Clinical Practice

Special Topic of Metabolic Syndrome Interview, November 2011

Scott M. Grundy

In our Special Topics analysis of Metabolic Syndrome, the researcher who claims the #1 spot by total citations is Dr. Scott M. Grundy, based on 55 papers with 9,264 total cites during the analysis period. Four of these papers appear on the top 20 papers lists as well. Grundy's record in Essential Science IndicatorsSM from Thomson Reuters includes 128 papers, the majority of which are classified under Clinical Medicine, cited a total of 27,552 times between January 1, 2001 and June 30, 2011.

Grundy is the Distinguished Chair in Human Nutrition as well as the Director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center at Dallas. He is also chief of the metabolic unit of the Veterans Affairs Medical Center in Dallas, Texas.

Below, he talks with correspondent Gary Taubes about his highly cited work as it relates to metabolic syndrome.

SW: As one of the prime movers in getting American physicians to recognize metabolic syndrome as an important risk factor for heart disease, how did it first come on your radar screen?

I came to metabolic syndrome from two angles. First of all, our research here was pointing in that direction, how important it was. But then my role in the National Cholesterol Education Program (NCEP) gave me an opportunity to bring that concept into clinical practice. I was involved with the NCEP and chair of that for many years.

We put out the guidelines for treating high cholesterol—from the National Institutes of Health (NIH) and the National Heart, Lung and Blood Institute (NHLBI)—and it became apparent that although we understood how to deal with cholesterol better, the country was being faced with an obesity epidemic. And in one of our first reports, we tried to emphasize that, but nobody paid any attention to it. The problem, of course, is that everybody talks about obesity, but nobody does much about it, or at least not so far.

In our last report in 2001—the NCEP Adult Treatment Panel 3 (ATP-3)—I got the idea and talked to the committee about it to change the emphasis from obesity to more of a medical issue and maybe then the doctors reading the guidelines would pay more attention. We then emphasized the metabolic complications of obesity, which is mainly metabolic syndrome. We added that in and said that was really important.

Those cholesterol guidelines carry a lot of weight. No doubt they set the guidelines for treating high cholesterol. That was the intention and that was successful. But now to our surprise, this metabolic syndrome really created a lot of attention and one of the reasons was that it actually attracted a lot of criticism—not just interest.

"If our patients paid attention to their risk earlier in life, a lot of disease could be prevented."

The American Heart Association (AHA) was behind it 100%, but the American Diabetes Association (ADA) was not. Or at least some of the people in the ADA didn't like it, because some how or another, they never totally understood it. They felt that metabolic syndrome was either not a syndrome or somehow conflicted with their view of the world. And oddly enough that seemed to help get it even more attention. It generated a lot of controversy, and that generated a lot of interest worldwide and really exceeded our expectations.

SW: What was the nature of the ADA's criticism and did you consider it valid?

Well, the ADA never took an official position on that, but the executive scientific officer of the ADA published some papers opposing the concept of metabolic syndrome. He was a very strong-minded guy and he orchestrated a kind of campaign against metabolic syndrome. He wrote a paper that had a lot of points in it. He thought it was premature and confusing, that it wasn't really necessary.

There are two ways to look at it. First is that metabolic syndrome is a collection of risk factors, which is what it is. Most people agree that those risk factors cluster together and that's what we call metabolic syndrome. He said there was no reason to create a metabolic syndrome, just treat the risk factors themselves—treat the high triglycerides or the high blood pressure, etc.—and don't worry about the fact that they occur together. Some people still take that view.

Our view was that all of these things are the result, mostly of obesity, so it's important for physicians to identify this combination of risk factors, so that they can be approached collectively. If you just focus on just one risk factor—the high glucose in diabetes, for example—you may not recognize the others adequately. The idea of metabolic syndrome is that it's a more global picture, so physicians could take a broader view of their patient and look at how everything fit together, and we thought that would be beneficial. It also directed the focus of treatment to lifestyle—controlling obesity, exercising more—in addition to just throwing drugs at each of the individual risk factors.

SW: How has our understanding of metabolic syndrome changed since ATP-3 was published a decade ago?

We published a paper in Circulation in 2009 in which we brought together many different organizations—the NIH, the AHA, the International Diabetes Foundation, the World Heart Federation and others—and put together a new consensus document. We wanted to bring everything together in a way that included as many of the organizations interested in this as possible. That one really kind of nails it down (Alberti KGMM, et al., "Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity," Circulation 120[16]: 1640-5, 20 October 2009).

SW: Did the definition of metabolic syndrome differ significantly from how you described it originally in the NCEP report?

Not very much. Let me give you a little background on that. Back in 1998, Sir George Alberti was one of the people in charge of a task force for the World Health Organization (WHO) in which they tried to define diabetes. Almost as an afterthought, they mentioned something about metabolic syndrome and suggested a clinical definition of it. When the NCEP's ATP-3 came out, that activated that WHO group—Alberti and Paul Zimmet from Australia.

They got very interested and they got together with the International Diabetes Foundation and they proposed an alternate definition. It was similar to ours, but a little different. Then the question was, which of these definitions should people use? A lot of papers were written on that, comparing the different definitions in different populations. So finally we all got together and said this is counterproductive, let's try to come up with the best consensus, the most consolidated definition that we can. That's what this paper is. We hoped it will put the issue to rest in terms of the clinical definition of metabolic syndrome.

SW: The antecedents of metabolic syndrome can be found in research back in the 1960s. Why do you think it took so long for the syndrome itself to be acknowledged and popularized? Do you think it required the obesity epidemic?

"The problem, of course, is that everybody talks about obesity, but nobody does much about it, or at least not so far."

I would say it did. There's another whole side of it and that's one of the reasons the diabetes people took exception. They thought that insulin resistance, which goes along with the diabetes, is the cause of the other risk factors—not only the high glucose, but the high triglycerides, low HDL, and hypertension. The theory, championed by Gerald Reaven, was that insulin resistance was the underlying cause of these risk factors. This led some people to call it the insulin resistance syndrome.

It's true that most of the people that have it are insulin resistant. But the alternate view, which I think is getting more to the heart of the problem, is that obesity causes most of these risk factors, and it makes people insulin resistant. I think that it's yet to be proven that insulin resistance is the cause of the other risk factors. That's debatable and complicated and never totally resolved. One way or the other, it was the obesity epidemic that really brought this to the fore.

SW: It's been a decade now since the NCEP published its cholesterol guidelines, on which you were the primary author—ATP-3. Where's ATP-4? That seems a long time to go without updating guidelines.

It's in the process, being developed. And one reason it's been so slow is that up until the metabolic syndrome, all the different risk factors were dealt with separately, by separate organizations in separate reports. Cholesterol and lipids were in one report by the NCEP. Another was hypertension and the guidelines there were by the Joint National Commission (JNC). Those JNC reports come out every few years telling doctors how to treat hypertension. Then there are obesity guidelines that are put out by the NIH. Diabetes guidelines, etc.

All of these are stand-alone guidelines. Since we became aware of metabolic syndrome and since it's become recognized that you don't want to just deal with each one separately in patients, the NHLBI decided that, well, okay, we'll bring all these things together, under one cardiovascular guideline. It's a very good idea.

Of course, once they started doing that, they found out that it was not so simple, because each one of those groups producing guidelines had a large constituency of researchers and academic people, who were very strongly attached to their risk factors. Now what's been decided is that the individual guidelines will continue separately, but still be pulled together under one heading in the cardiovascular disease guideline. That requires another committee to try to amalgamate that.

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