The Metabolic Syndrome: The Emperor Needs Some Consistent Clothes

Response to Davidson and Alexander

Drs. Davidson (1) and Alexander (2) suggest that the so-called “metabolic syndrome” has reached sufficient prominence, i.e., it has “come of age,” and that it deserves a new section in Diabetes Care. While enthusiasm about the “metabolic syndrome” among professionals, the media, and the public has developed rapidly and perhaps “come of age,” a more apt description of its scientific status is that “this emperor needs some consistent clothes” (3). Given the following realities of the state of the metabolic syndrome at present, healthy caution is necessary. 1) There is no consensus about the definition of the metabolic syndrome (4). 2) The oft-used National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) recommendations for the diagnosis of the metabolic syndrome, which is assessment of three out of five elements (5), do not reflect an evidence-based process but at best a “consensus among experts” whose recommendations will no doubt change over time (what about C-reactive protein?) (6). 3) Neither “equity” in the prevalence of the metabolic syndrome among racial/ethnic groups (7) nor pathophysiologic parity among the five elements of the ATP III definition of the metabolic syndrome exist (8). 4) The cut points for each of the five elements of the ATP III definition of the metabolic syndrome are presently arbitrary. For example, has the prevalence of the metabolic syndrome now reached “hyperepidemic” proportions with the new and more inclusive definitions (9,10) of impaired fasting glucose and prehypertension? 5) The five elements of the ATP III definition of the metabolic syndrome, including the recommended cut points for these elements, do not reliably indicate the presence of “insulin resistance” (11). 6) In fact, there is no agreement that insulin resistance is the basic abnormality underlying the metabolic syndrome, with emerging evidence (12,13) of the importance of “ectopic fat deposition” preceding insulin resistance. 7) Although a code for the metabolic syndrome has been established (14), coding does not equate with reimbursement (nor, in the mind of the authors, should it… yet). 8) Finally (and most importantly), there is no evidence that interventions to treat the entire metabolic syndrome as defined by NCEP/ATP III (versus appropriate interventions directed to the individual parts, e.g., hyperlipidemia, hypertension, etc.) are efficacious, let alone cost-effective. In summary, given that this is a situation where the basic etiology is unclear, the recommended diagnostic criteria (both the elements and cut points) are not evidence based, and no rigorous scientific evidence exists to indicate that treating the entire panoply of elements in the so-called metabolic syndrome beyond individual risk factor treatment guidelines matters (i.e., what is gained beyond some new nomenclature), the concept of the metabolic syndrome may be “coming of age,” but the practical clinical and public health significance of this interesting entity remains “embryonic” (15,16).