A Paradigm Shift and New Therapeutic Options for the Metabolic Syndrome

Abstract

The metabolic syndrome, characterized by obesity, dyslipidemia, insulin resistance and hypertension, increases the risk of cardiovascular morbidity and mortality. Most current views on the pathogenesis of the metabolic syndrome and its existing treatments have been dominated by a glucocentric approach: the glycemic response to insulin is suboptimal, with dire metabolic consequences. Such consequences are compensatory hyperinsulinemia, ?? cell glucotoxicity and lipotoxicity and the deposition of amyloid in pancreatic islets, with concomitant inflammation, endothelial dysfunction, a procoagulant state and dyslipidemia. In addition, these views have been applied on the premise that effector molecules involved in disease pathogenesis or response to therapy are invariant across the population.However, most current therapies have limited efficacy and limited tolerability.