ABSTRACT
The very concept of' 'insulin resistance'' originated with the availability of insulin therapy for treatment of diabetes well over 50 years ago. At that time, clinical observations suggested that there were two groups of diabetic patients who were roughly divided by their response to the glucose-lowering effects of exogenously administered insulin. These two groups generally corresponded to the present- day classifications of type 1 and type 2 diabetes. The term insulin resistance was then coined to describe diabetic patients who had a markedly elevated exogenous insulin demand (e.g., requiring more than 200 U of insulin a day), often in association with antibodies induced by the insulin preparations available at the time (e.g., bovine and porcine insulin). The term continued to evolve with the use of the radioimmunoassay for insulin in the 1960s, which distinguished type 1 diabetic patients, with an absolute insulin deficiency, from type 2 patients, who have relatively normal or elevated levels. It soon became apparent that there were many individuals with normal glucose levels, but relatively high insulin levels. Further research conducted in the 1970s and 1980s (with in vivo metabolic techniques that assessed glucose uptake during insulin infusions and with tissues from insulin-resistant patients studied ex vivo) demonstrated conclusively that insulin resistance was due to an impaired insulin action in peripheral tissues such as fat, muscle, and liver. These studies have led to the cuirent-day definition of insulin resistance as a clinical state in which a normal or elevated insulin level produces an impaired biological response.
