ABSTRACT
Insulin resistance, defined as an attenuation of normal insulin action, is a key pathogenic phenomenon observed in the natural history of type 2 diabetes (1,2). Development of this condition in insulin-sensitive peripheral tissues (e.g., muscle and fat) results in hyperinsulinemia, a compensatory mechanism required to maintain normal or near-normal glucose levels. This ‘‘compensated’’ state may be maintained for many years. Once pancreatic β-cell dysfunction occurs, however, inability to compensate for the increased insulin resistance results in clinical hyperglycemia and the diagnosis of type 2 diabetes is then apparent and can be made on clinical grounds. As such, insulin resistance can be considered an initial pathophysiological event leading to, and premonitory of, type 2 diabetes (3-5). Intensive research has been aimed at identifying the cellular mechanisms responsible for insulin resistance and providing a framework for designing pharmacological therapies to alleviate the condition. This chapter will review basic research studies evaluating the cellular defects contributing to insulin resistance, describe methods to clinically assess this variable, discuss associated clinical risk factors, and provide an overview of management options.
