Paul Zimmet Discusses the Evolution of Metabolic Syndrome
Special Topic of Metabolic Syndrome Interview, September 2011
Along with the National Cholesterol Education Program's ATP-3 definition, published in 2001, numerous other definitions appeared in the literature, and it was quite clear that researchers, clinicians and various peer-reviewed publications were using different definitions of rates for the same condition. It was all very confusing.
In 2005, Alberti and I convened the International Diabetes Federation (IDF) Task Force on Epidemiology and Prevention of Diabetes to try and develop a definition that could be used globally and allow all data to be comparable. In that sense, our WHO definition was premature, as it was impractical to measure insulin resistance at an individual level without a sophisticated insulin clamp technology.
The IDF definition was published and launched in Berlin in 2005 at the 1st International Congress on Prediabetes and the Metabolic Syndrome. Having realized the great developing interest in the metabolic syndrome, Alberti and I had joined two Israeli scientists, Pesach Segal and Avi Karasik, to set up the first international forum on the syndrome. Almost immediately, a publication from the American Diabetes Association (ADA) tried to "kill" the syndrome. It engendered quite an exchange of views, both interpersonal and in press. It is a story in itself how we feel the ADA got it wrong, and caused as much confusion as existed before we published the IDF definition.
The main point that Alberti and I were trying to make with redefining the metabolic syndrome was to make it a practical tool that could be used right down to the primary health care level to detect persons at high risk of cardiovascular disease and diabetes. This is the main utility for the metabolic syndrome.
The obvious question is how did the ADA get it wrong, or why, in your opinion?
"The fact that we were able to demonstrate that there were approximately one million people with diabetes in Australia and that the number had increased about 300% over the previous 20 years gave a new public health perspective to the challenges of diabetes."
Firstly, they asked seven or so questions. Does it exist? Is it a syndrome? Is it precisely defined? Is there uncertainty about its pathogenesis? How useful is it for predicting diabetes and cardiovascular risk? Is the cardiovascular disease risk greater than the sum of the components? Does it have medical value? Those were the sorts of questions they raised.
Our feeling is that it clearly does exist. In people with diabetes, some 60-70% have a number of the other components of the syndrome. And the definition of a syndrome precisely fits this diagnosis. Get any dictionary and you'll find something along the lines of a set of symptoms or conditions that occur together and suggest the presence of a certain disease or increased chance of developing disease.
As to the question of whether it is precisely defined, we agreed that there were many competing definitions in use. That's why Alberti and I convened the IDF Task Force, to try to come up with one precise definition that could indeed be used globally.
As for the pathogenesis, we all agree that there are still questions about what it is. Metabolic syndrome is a group of risk factors and the major question is whether there is just one defining pathological or metabolic abnormality that causes all these factors to arise or do they have different origins. It's quite clearly useful for predicting diabetes and cardiovascular disease. That's been well established. So I think the ADA got it wrong there.
It certainly has medical value. Our main thrust all along has been that if you get someone in your consulting room, even down at the primary health care level, and that person has a number of these metabolic syndrome risk factors, then it tells the general practitioner, the physician, that they should check it out further. If a patient comes in with hypertension, check the other risk factors and it's very likely that the patient will have them. It gives a very good head start in preventing diabetes and cardiovascular disease.
The ADA is a great organization; there's no question about it. But a lot of countries around the world that don't have their own guidelines in this area look to the ADA for guidance; they react to position statements like the one that came out of the ADA and then they get very confused. The WHO says there is a metabolic syndrome. The IDF says so. But the ADA doesn't. What's going on?
The remarkable thing is that since that controversy, we've found a much better way forward. Because of this discrepancy between ATP-3 and the IDF definition, Alberti and I worked very closely with Robert Eckel and Scott Grundy (who I think of as the "Billy Graham of Metabolic Syndrome" for his evangelical work getting people to accept and understand it), and we worked with several international organizations to see if we could come up with a single definition that could be used globally and thereby have standardization. The main difference between ATP-3 related to the criteria for central obesity and also to the fact that, in the IDF definition, the inclusion of central obesity was an essential component.
"The main point that Alberti and I were trying to make with redefining the metabolic syndrome was to make it a practical tool that could be used right down to the primary health care level to detect persons at high risk of cardiovascular disease and diabetes. This is the main utility for the metabolic syndrome."
After some soul-searching and compromise we ended up with agreement on a single definition which was published in Circulation in 2009—"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 of the Study of Obesity." This consensus was achieved through the participation of the groups listed above, all interested in the concept of the metabolic syndrome and its continuing recognition.
That 2009 paper had many international organizations as co-signers, but the ADA was not among them. Is that organization still holding firm in its opposition to the concept of metabolic syndrome?
The ADA people were invited, but I don't think they were too interested in coming back into the debate.
Several of your other papers discuss the prevalence of it in different parts of the world or in different types of populations. Which area and which populations are most at risk? Have any come as a particular surprise?
It comes as quite a surprise that between 30-40% of Australians and an even higher proportion of Americans have the metabolic syndrome, according to either the IDF or the ATP-3 definition.
You're one of the principal investigators of the AusDiab Study. Could you give us an overview of this study, and tell us what sort of discoveries or advances in Metabolic Syndrome might have come about over the years thanks to AusDiab?
I was able to convince our Minister of Health, at the time, the Honourable Michael Wooldridge, that we needed a National Study of Diabetes and Obesity in Australia, hence AusDiab. The idea was to ascertain the prevalence of diabetes, obesity, and cardiovascular risk factors on a national basis for the first time. Studies showed that over 7.0% of the adult population of Australia had diabetes and a further 16.0% had pre-diabetes. The prevalence of obesity and overweight was around 60.0% in both males and females and the overall prevalence of the metabolic syndrome was 25% and over 40% in people with diabetes.
This was a landmark study for Australia, one of the largest national studies of diabetes globally and the Study has had a profound effect on public health action for diabetes. The fact that we were able to demonstrate that there were approximately one million people with diabetes in Australia and that the number had increased about 300% over the previous 20 years gave a new public health perspective to the challenges of diabetes.
Subsequently, the Federal Government implemented prevention programs for diabetes and, based on the AusDiab data, a risk calculator for future diabetes has been developed and is available on the Internet and widely used in the primary health care setting. The Study highlighted also, through the metabolic syndrome findings, the need for the control of other heart disease risk factors, such as cholesterol, obesity, and hypertension.
How big of a societal problem/threat is metabolic syndrome, in your opinion?
The metabolic syndrome and its components are a great threat to the overall health of not only Australian society but globally. I tend to look now at the metabolic syndrome as being the main issue and that each of the components—including glucose intolerance (including diabetes), dyslipidemia, obesity, and hypertension—need to be treated individually to reduce the risk of vascular disease outcomes. If you also throw into the equation sleep disturbances, such as sleep apnea and lesser degrees of sleep disorders, we have a combination of factors which constitute the greatest threat to human health now and in the future.