Insulin resistance can be broadly defined as a subnormal biological response to normal insulin concentrations. By this definition, it may pertain to many biological actions of insulin in many tissues of the body. Typically, however, in clinical practice, insulin resistance refers to a state in which a given concentration of insulin is associated with a subnormal glucose response . The term first came into use several years after the introduction of insulin therapy in 1922 to describe occasional diabetic patients who required increasingly large doses of insulin to control hyperglycemia. Most of these patients developed insulin resistance secondary to antibodies directed against the therapeutic insulin, which at that time was both impure and derived from non-human species . Antiinsulin antibodies are rare in patients treated with recombinant human insulin, and the spectrum of clinical disorders in which insulin resistance plays a major role has changed markedly. Insulin resistance, rather than being a rare complication of the treatment of diabetes, is now recognized as a component of several disorders, including the following (table 1):
- Extreme insulin-resistance syndromes, such as the type B syndrome with autoantibodies against the insulin receptor , and rare inherited disorders, such as Leprechaunism with insulin-receptor mutations  and the lipodystrophic states .
- Impaired glucose tolerance and type 2 diabetes mellitus.
- Obesity, stress, infection, uremia, acromegaly, glucocorticoid excess, and pregnancy, which cause secondary insulin resistance.
- Common disorders such as the metabolic syndrome, hypertension, hyperlipidemia, coronary artery disease, the polycystic ovary syndrome, and ovarian hyperthecosis, in which the mechanism of the associated hyperinsulinemia is unknown. (See "The metabolic syndrome (insulin resistance syndrome or syndrome X)" and "Clinical manifestations of polycystic ovary syndrome in adults" and "Ovarian hyperthecosis".)
Possible mechanisms for the development of insulin resistance are discussed elsewhere. (See "Pathogenesis of type 2 diabetes mellitus".)
DEFINITION AND QUANTIFICATION
Insulin resistance may be defined as a subnormal glucose response to both endogenous and exogenous insulin.
Resistance to endogenous insulin — Resistance to endogenous insulin is identified by high serum insulin concentrations in association with blood glucose concentrations that are normal or high. In practice, we measure serum insulin only when evaluating patients with clinical features of extreme insulin resistance (see 'Clinical spectrum' below).