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A recent statement published by the American Diabetes Association (ADA) andthe European Association for the Study of Diabetes(EASD)1 suggestsmetabolic syndrome isn't really a syndrome, and should not be a diagnosis usedin primary care.
If the authors of the statement wanted to spur debate about metabolicsyndrome, they may have generated more than they bargained for. Since thepaper was released in late August, the story has been picked up by majornational news outlets, including USA Today and The WashingtonPost.
Known variously as syndrome X and insulin resistance syndrome, a cluster ofsymptoms linked to cardiovascular risk has been recognized since beingdescribed in 1988 by Gerald M. Reaven,MD.2
While most clinicians have become aware of metabolic syndrome since then,there is little consensus about its definition and meaning. The two mostwidely accepted definitions of metabolic syndrome have several significantdifferences (see sidebar, "Differing Definitions of MetabolicSyndrome"). Do the definitions refer to the same condition, or do thedifferences belie an ambiguity and uncertainty about the diagnosis?
For many years, ADA has raised the alarm over metabolic syndrome withoutformulating an official position statement. Recently, a group of top diabetesleaders decided to take a hard look at the science.
"When we went to review the literature and come to a decision, wefound, much to our surprise, that the literature raises more concerns andquestions than it answers," says Richard Kahn, PhD, ADA's chiefscientific and medical officer.
SUPPOSING A SYNDROME
One of the main questions about metabolic syndrome is whether it is asyndrome at all. Traditionally, a syndrome is defined as a group of signs andsymptoms with a common underlying pathology. Some argue that although thesymptoms of metabolic syndrome often appear together, they may reflectdifferent disease processes.
Other experts contend that the term "syndrome" is used often inmedicine, as in "acute coronary syndrome." Acute coronary syndromecan have multiple causes and can manifest itself in a variety of ways. Still,few doubt that it exists.
Kahn is careful to point out that the risks of metabolic syndrome are real,even if the terminology is questionable. He suggests using "metabolicrisk" or "cardiometabolic risk" to describe the"unexpected clustering of cardiovascular risk factors related to alteredmetabolism.
"It's useful as a concept, but not using the word `syndrome,'"Kahn says.
AMBIGUOUS CRITERIA
The ADA/EASD paper points out specific areas of concern about how thediagnosis of metabolic syndrome is currently used. Criteria are ambiguous orincomplete, and the rationale for thresholds is ill-defined, the authorswrite. Although both the third report of the National Cholesterol EducationProgram's (NCEP) Adult Treatment Panel III (ATP III) and the World HealthOrganization (WHO) definitions include waist size and its factors, forexample, there is no consensus on how to measure waist size. Similarly,clinicians are left to wonder, does a blood pressure have to be 130 mmHgsystolic and 85 mmHg diastolic, or 130 mmHg systolic or 85mmHg diastolic?
The value of including diabetes in the definition is questionable, thepaper says, and insulin resistance as the unifying etiology is uncertain.There is no clear basis for including or excluding other cardiovasculardisease (CVD) risk factors, and the CVD risk value is variable and depends onthe specific risk factors that are present.
Ultimately, the CVD risk associated with metabolic syndrome appears to beno greater than the sum of its parts, ADA and EASD conclude. Treatment of thesyndrome is no different than the treatment for each of its components. Themedical value of diagnosing the syndrome is unclear, the authors say.
DEBATING THE MERITS
Reaven says he "agree[s] totally" with the ADA/EASD report. Ina paper published in Clinical Chemistry earlier this year, Reavenargued that the criteria for metabolic syndrome are arbitrary and without ascientificbasis.3
The label of metabolic syndrome "does more harm than good" inthe primary care setting, Reaven says. "It's a silly idea. It has noutility, conceptually or practically, for the primary carephysician."
Others assert that metabolic syndrome is a useful diagnosis with a properplace in primary care. The term is an important way to educate patients aboutthe connection between their lifestyle, health risks, and medical outcomes,contends Darwin Deen, MD, director of medical student education in theDepartment of Family and Social Medicine at the Albert Einstein College ofMedicine of Yeshiva University, Bronx,N.Y.
In a 2004 paper, Deen argued forcefully for bringing the concept ofmetabolic syndrome to the attention of primary carepatients.4
"Metabolic syndrome is a prototype of the way in which we can nowidentify those patients who are at highest risk of bad outcomes," Deensays. "It's vitally important for physicians to begin communicating thatinformation to patients."
Kahn says that by releasing the paper, ADA and EASD hope to spur criticalanalysis of how metabolic syndrome is defined, fine-tuning of upper and lowercut-off points, and an evidence-based analysis of adding or replacing CVD riskfactors.
In the meantime, the group offers specific recommendations:
Differing Definitions of Metabolic Syndrome
According to the third report of the National Cholesterol Education Program(NCEP) Adult Treatment Panel III (ATPIII),1 adults whoare diagnosed with metabolic syndrome must have three or more of thefollowing:
150 mg/dl 130/85 mmHg 110 mg/dl (100 mg/dl may be applicable) The definition of metabolic syndrome put forth by the World HealthOrganization (WHO),2on the other hand, begins with poor glucose metabolism—diabetes,impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or insulinresistance—and at least two of the following:
150 mg/dl or HDL cholesterol <35 mg/dl in menand <39 mg/dl in women 140/90 mmHg 30 mg/g. References
2. Reaven GM: Banting lecture 1988. Role of insulin resistance inhuman disease. Diabetes 37:1595–1607, 1988.[Abstract]
3. Reaven GM: The metabolic syndrome: Requiescat in pace.Clin Chem 51:931–938, 2005.
4. Deen D: Metabolic syndrome: Time for action. Am FamPhysician 69:2875–2882, 2887–2888, 2004.[Medline]
1. Expert Panel on the Detection, Evaluation, and Treatment of HighBlood Cholesterol in Adults: Executive summary of the third report of theNational Cholesterol Education Program (NCEP) Expert Panel on the Detection,Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult TreatmentPanel III). JAMA 285:2486–2497, 2001.
2. World Health Organization: Definition, Diagnosis, andClassification of Diabetes Mellitus and Its Complications: Report of a WHOConsultation. Geneva, World Health Organization, 1999.
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