The Metabolic Syndrome: Requiescat in Pace‪.‬

Values for insulin-mediated glucose disposal vary continuously throughout a population of apparently healthy individuals, with at least a sixfold variation between the most insulin sensitive and most insulin resistant of these individuals. The more insulin resistant a person, the more insulin must be secreted to prevent decompensation of glucose tolerance. Insulin resistance is not a disease, but a description of a physiologic state, and approximately one third of an apparently healthy population is sufficiently insulin resistant to be at increased risk to develop a cluster of abnormalities and related clinical syndromes. The primary value of the concept of insulin resistance is that it provides a conceptual framework with which to place a substantial number of apparently unrelated biological events into a pathophysiological construct. In contrast, the metabolic syndrome was introduced as a diagnostic category to identify individuals that satisfy three of five relatively arbitrarily chosen criteria to initiate lifestyle changes with the goal of decreasing risk of cardiovascular disease. Consequently, the value of the notion of the metabolic syndrome must be considered not in pathophysiologic terms, but as a pragmatic approach to obtain a better clinical outcome. In this review, an effort is made to critically evaluate the concept of the metabolic syndrome, the criteria chosen to identify individuals with the syndrome, and the clinical utility of making, or not making, a diagnosis of the metabolic syndrome. In 2001, the Adult Treatment Panel III (ATP III) [1] of the National Cholesterol Education Program proposed criteria for diagnosing what they designated the metabolic syndrome (1). Since the original report by Ford et al. (2) in 2002 describing the prevalence of the metabolic syndrome in the United States, multiple papers have been published addressing the same issue. As an example of this phenomenon, I cite 14 articles (3-16) that represent a small sample of those published on this topic in 2004; they were based primarily on retrospective analyses of population-based studies, conducted in several countries, with experimental data gathered for a variety of different reasons, in groups differing in terms of age, sex, and ethnicity. Although this burst of creative activity has led to an enormous amount of published data, it is not clear that it has led to the delivery of any new information of significant utility to the practicing clinician. In fact, as will be discussed subsequently, if taken at face value, there is a real possibility that use of the ATP III criteria could do more harm than good. At the least, it might be useful to take a somewhat skeptical look at the clinical implications of implementing the diagnostic criteria proposed by the ATP III, and the effort to address this issue is the justification for this presentation.