Metabolic Syndrome: A Work in Progress, but a Useful Construct

The metabolic syndrome is a construct that has come into common usage over the last few decades. In 1956, Jean Vague1 first demonstrated that upper-body obesity determined predisposition to diabetes mellitus, atherosclerosis, gout, and renal calculi; however, it was the presentation of this concept by Gerald Reaven in his Banting Lecture in 19882 that initiated the current focus on this entity as a clinical and pathological construct. Dr Reaven suggested that 3 major conditions—non–insulin-dependent diabetes mellitus (type 2 diabetes mellitus), hypertension, and coronary artery disease—had an causal commonality (resistance to insulin-stimulated glucose uptake and hyperinsulinemia) and referred to this constellation of abnormalities as “syndrome X.” He did not include abdominal obesity in the original description, nor did he comment significantly on a potential clinical role for his observations. In fact, his concluding sentences stated, “What remains to be seen is the magnitude of the role that resistance to insulin-stimulated glucose uptake plays in the etiology of human disease. I can only hope that this presentation has outlined the possibilities for future efforts to answer this question.” Response by Kahn p 1818 Since that time, this construct has evolved conceptually and functionally into an entity that many refer to as a “syndrome.” More recently, there have been many questions about the legitimacy of this designation, summarized by Kahn et al3 in a September 2005 position statement for the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Their comments called into question many of the assumptions that underlay the designation of “syndrome,” and they posed the following key questions: How clear is the existing definition of the metabolic syndrome for diagnostic purposes? How useful is the syndrome definition in predicting cardiovascular disease (CVD) risk? Do the individual components of the syndrome convey “risk” …