Editorial [ The Metabolic Syndrome: Revisiting the Concept, the Diagnosis and the Treatment (Part-I)Guest Editors: John H. McNeill and Vijay Sharma ]

We are faced with an alarming epidemic of obesity, diabetes and cardiovascular disease. For this reason, the Metabolic Syndrome (MetS) has been receiving a great deal of attention both from the scientific community and from the general public. A recent statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) called for the concept of the MetS to be re-evaluated (1). The MetS serves two purposes: it is a concept and it is a diagnosis. As a concept, the MetS highlights the fact that its components tend to cluster together. This has raised awareness of cardiovascular risk among health care workers and the general public. It has also provided a conceptual framework in which that risk can be managed. There is, therefore, no doubt that the concept has been useful. The main controversy which surrounds the concept comes down to one key question: what is required to make a syndrome? In a syndrome, a number of symptoms, signs and/ or physiological traits are related to a single underlying cause. In Cushing's syndrome, the cause is corticosteroid excess. In the Sleep Apnea/ Hypopnea syndrome, the underlying cause is intermittent obstruction of the airway during sleep. Both of these syndromes have a clear definition. Corticosteroid excess or airway obstruction may be caused by a wide range of factors, but there is a clear unifying feature. Furthermore, once the diagnosis of either syndrome is made, that diagnosis influences the subsequent investigation and treatment of the patient. When the existence or usefulness of a syndrome is examined, this is the standard it is expected to meet. The MetS does not measure up to this standard partly because the necessary research is still ongoing, and partly because it is very different in nature from the syndromes against which it is being judged. The MetS is an asymptomatic syndrome; its components are all physiological traits. This immediately makes its existence as an entity harder to grasp and conclusively prove than, for example, Cushing's syndrome. The proposed unifying feature of its components is insulin resistance, which is itself a very heterogeneous and complex physiological trait. Insulin resistance can occur in the context of a far wider neuroendocrine dysfunction, and can be regarded as a cause, a consequence, a sustainer and a marker of this dysfunction. Furthermore, whole body insulin resistance is the collective result of insulin resistance, which occurs at the cell, tissue and organ levels. Finally, there are many mechanisms at every level, by which insulin resistance can occur. Unifying features of all forms of insulin resistance will doubtlessly be found, and several such features are currently being defined. However, when one takes a global look at the intimidatingly large number of factors, which act either to cause insulin resistance or mediate its proposed effects, the emerging picture is one of a highly complex causal network. Within such a network, interrelated physiological traits will be found to cluster. However, there is no simple underlying cause, but rather a causal network. Is this still a syndrome? We believe that it is, because the clustering of risk factors is related to a meaningful underlying cause, albeit one which is less straightforward than the elevated corticosteroid levels in Cushing’s syndrome. The usefulness of the Metabolic Syndrome as a diagnosis requires much further study. There are several proposed definitions of the MetS accompanied by several confouding questions such as; Which should be used and in which situations? Which group of patients should we seek to identify: patients with insulin resistance or patients with increased cardiovascular risk? Does a diagnosis of the MetS influence the clinical management? However, no specific treatment strategy exists at the present time. Should the MetS be treated as a distinct all-or-nothing diagnosis, or simply as a conceptual framework? There has been concern that the use of the MetS as a diagnosis may lead clinicians to ignore individual risk factors in patients who do not meet the criteria for diagnosis. There is, to our knowledge, no evidence that this is the case. Does the use of the MetS as a diagnosis improve patient outcomes? This is a key question which has not been adequately addressed. Does the diagnosis of the MetS change the management of the patient? There is, at present, no specific treatment strategy for the MetS, it is not yet clear what is required over and above the management of the individual risk factors. The aim of this two-part special issue of Current Vascular Pharmacology is to provide a broad overview of the experimental and clinical research, which has sought to answer these important questions. The MetS, both as a concept and a diagnosis, will be re-examined. Future directions for research to elucidate the pathogenesis of the MetS and to determine the clinical utility of the MetS as a diagnosis will be suggested............