Molecular Basis of Insulin Resistance and Its Relation to Metabolic Syndrome

The metabolic syndrome is an agglomeration of interrelated risk factors that is associated with nearly 5-fold increased risk for type 2 diabetes mellitus (DM) and a 2-fold increased risk of coronary artery disease (CAD) [1]. Reaven first suggested this cluster of metabolic abnormalities in 1988. It is characterized by insulin resistance, visceral adiposity, dyslipidemia and a systemic pro-inflammatory and pro-coagulant state [2]. Insulin resistance is defined as reduced insulin action in metabolic and vascular target tissues, hence higher than normal concentration of insulin is required to maintain normoglycemia. On a cellular level, it indicates an inadequate strength of insulin signaling from the insulin receptor downstream to the final substrates of insulin action involved in multiple metabolic and mitogenic aspects of cellular function [3].