Affiliation: Dept. of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of South Carolina School of Medicine, Two Medical Park, Suite 502, Columbia, SC 29203, USA.
Communities all over the world are confronted with an alarming rise in the rates of obesity, physical inactivity, and associated metabolic diseases. Central adiposity seems to go hand-in-hand with established risk factors like elevated blood pressure, dyslipidemia, and hyperglycemia. Although genetic and environmental influences modulate the ultimate risk, this clustering of chronic insults to the endothelium takes its toll in the form of atherothrombotic cardiovascular events. Insulin resistance, accepted as the underlying etiology of type 2 diabetes, appears to have other deleterious consequences, even in the absence of hyperglycemia. In 1988 Gerald Reaven advocated insulin resistance to be the core defect in his description of ‘syndrome X’, subsequently renamed as the currently-accepted ‘metabolic syndrome’ and identified by diagnostic criteria intended for clinical use. In recent years there has been an explosion of basic and clinical research pertaining to the metabolic syndrome, generating intense interest and controversy. The cellular and vascular accompaniments have shed some light into its pathophysiology. Heightened, low-grade inflammation as well as a continuum of vascular insults from endothelial dysfunction to advanced atherosclerosis has been studied in the context of the syndrome. Inflammatory biomolecules have been speculated be markers and mediators of oxidative stress and endovascular toxicity. Creactive protein has been the most extensively studied. ‘Adipocytokines’ are inflammatory agents that originate from adipose tissue, thus changing the concept that fat is a metabolically active organ rather than inert tissue. The effect of lifestyle interventions and pharmacologic agents is being investigated. Further research promises to elucidate the complex pathogenetic dynamics at play in the metabolic syndrome and lead to possible therapeutic opportunities.