Although insulin has a number of metabolic effects, insulin resistance is usually defined as a state in which physiological levels of insulin have a decreased biological action on plasma glucose. Glucose uptake by skeletal muscle and adipose tissue and suppression of hepatic glucose production are affected. To maintain normoglycemia in the insulin-resistant state, excessive compensatory increases in insulin are required which may eventually lead to a decline in and exhaustion of insulin-producing pancreatic beta cells, the development of glucose intolerance, and, finally, type 2 diabetes. Insulin resistance is associated with a constellation of traits other than glucose intolerance, including visceral obesity, dyslipidemia, hypertension, and a prothrombotic state. Epidemiological studies consistently show an independent association between insulin resistance and risk of cardiovascular disease. The term insulin resistance is often used interchangeably with decreased insulin sensitivity or reduced insulin action. There are wide differences in the ability of insulin to mediate glucose disposal among individuals. Insulin sensitivity is a continuous variable, and distinguishing normal and abnormal insulin sensitivity in individuals is difficult because there is no uniform quantitative definition of what constitutes insulin resistance. Individuals are considered insulin resistant if they have normal glucose tolerance but lie in the most insulin-resistant quartile of a given population. In individuals with normal glucose tolerance, insulin resistance can vary by four- to tenfold, with some measures of resistance not differing substantially from those of people with impaired glucose tolerance (IGT) or type 2 diabetes.