Dallas, TX - In the past year, a disagreement over the clinical usefulness of a metabolic-syndrome diagnosis has engaged those in cardiology and in the diabetes world. The contentiousness of the syndrome reached a pinnacle last summer with the publication of two disparate clinical statements taking nearly opposite positions [1,2]. A new review article seeks to bridge the recent divide, with the goal of increased attention for the management of affected patients [3].

"The metabolic syndrome is a condition that causes an increased risk of both diabetes and cardiovascular disease," author Dr Scott Grundy (University of Texas Southwester Medical Center, Dallas) told heartwire. "It is really getting to be an enormous problem. In the cardiovascular world, including the American Heart Association [AHA] and the National Heart, Lung, and Blood Institute [NHLBI], we would like clinicians to recognize the multiple-risk-factor patient and to get more intensive intervention with lifestyle, and if necessary with drugs, and also to recognize that these risk factors all go together."

Published online in the February 23, 2006 issue of the Journal of the American College of Cardiology, the review comes just a few months after the AHA and the NHLBI teamed up to produce a scientific statement on the diagnosis and management of metabolic syndrome. The statement, chaired by Grundy, was based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines published in 2001.

Prior to the release of the AHA/NHLBI statement, however, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) issued their own statement discouraging the use of the term metabolic syndrome. The two statements pointed to a divide in how cardiologists and diabetologists should diagnose and treat the syndrome.

"Metabolic syndrome is simply not a disease," Dr Richard Kahn (chief scientific and medical officer, ADA) told heartwire at the time. "It's been blown way out of proportion, and it's taken on a life of its own."

Grundy said this recent review was written at the request of the journal, to clear up issues raised by some in the diabetes community. The paper was also intended to update cardiologists about metabolic syndrome and "bring them into the picture a little bit more."

As noted in previous reports, including the AHA/NHLBI statement, an individual is diagnosed as having the metabolic syndrome if abnormal levels of three of the following exist: increased waist circumference, elevated triglycerides, reduced HDL cholesterol, elevated blood pressure, or elevated fasting glucose.

Grundy told heartwire that while the cardiovascular community has embraced the concept of risk-factor clustering as a syndrome, not everybody in the diabetes community has been as receptive.

"The diabetes world sees this syndrome in a somewhat different way because they were involved in the evolution of the concept of insulin-resistance syndrome and its relationship to cardiovascular risk factors," said Grundy. "The cardiology world is very interested in this as it relates to cardiovascular risk factors, but because the diabetologists had one view of where it was coming from they felt some ownership of this syndrome. On the other hand, it does predict diabetes as well, so I think we've got two fields that look on this a little bit differently, and that gives rise to a little bit of tension."

Grundy stressed the gap between the two disciplines is not a clear-cut divide, with most clinicians seeing the overlap into the cardiovascular and diabetes domains. But for some, including Dr Gerald Reaven (Stanford University School of Medicine, CA), credited with first elucidating the link between insulin resistance and hypertension, hyperlipidemia, and diabetes and with coining the term syndrome X, there is no need for a metabolic-syndrome diagnosis at all. As he earlier told heartwire: "If you have type 2 diabetes, the ADA and European Diabetes Policy Group guidelines recommend you measure the lipids, measure the BP, all those things, and you're supposed to act if the patient has one of those things wrong: lower the glucose and take care of the lipids. Fine! Terrific! So what advantage is there to diagnosing metabolic syndrome? Zero. If you have diabetes, there are clear-cut guidelines for how to treat diabetes and the common consequences of the diabetes. So why the hell do you need to make a diagnosis of metabolic syndrome?"

In cardiovascular medicine, said Grundy, there is a bigger drive to recognize that these risk factors cluster together with a common etiology, in which obesity plays a big role.

"For that reason, there is a tendency to look on this as a unified problem, particularly for lifestyle change, where we can treat all of these risk factors at the same time, but also take into account that one risk factor does affect the overall risk profile," he said. "All these risk factors, together, affect the overall risk of the patient, so you modify the treatment of the individual risk factors depending on whether the metabolic syndrome is present. I think the idea that you treat each risk factor separately goes a little bit against the current thinking by the cardiovascular world."

The cornerstone of treatment of the metabolic syndrome remains lifestyle modification, said Grundy. In fact, the ATP III guidelines embedded the metabolic syndrome into the cholesterol guidelines to reinforce concerns about obesity and to promote lifestyle therapies, including weight reduction, increased physical activity, and a low-fat diet.

Not surprisingly, the pharmaceutical industry has recognized the enormous market, especially if a pill could be developed to target a number of risk factors within the metabolic-syndrome cluster. Rimonabant (Sanofi-Aventis), for example, has grabbed headlines recently because it seems to improve multiple components of the metabolic syndrome at once. In RIO-EUROPE, investigators conducted analyses specifically in patients with metabolic syndrome and touted an impressive 50% drop in the number of patients with metabolic syndrome after two years on the drug.

"When the ATP panel put the metabolic syndrome forward, the concern was about obesity, and the need for long-term lifestyle intervention," said Grundy. "It created a lot of interest, and what happened immediately was that a lot in industry began to think, 'If we could get an indication for metabolic syndrome and could develop drugs in this area, we could really cash in.' Some people feel, and I'm not one of them, that the syndrome has been taken over by the pharmaceutical industry, who see it as an opportunity to develop drugs. Personally, I think if we could develop drugs that are effective and are safe, it's a challenge for the drug companies to work on and I'd be all for that."

Grundy noted that all of the drugs currently targeting multiple risk factors, including rimonabant, still have hurdles to overcome. In the meantime, new drug development should not detract from the priority given to lifestyle modification, he said.