Insulin Resistance Is Not Necessarily an Essential Component of Type 2 Diabetes 1

Abstract

Insulin resistance and impaired insulin secretion are usually present in patients with classic type 2 diabetes as well as in most people with impaired glucose tolerance (1, 2). Both play important roles not only in determining whether diabetes occurs, but also in determining the magnitude of the accompanying hyperglycemia and other metabolic abnormalities (3, 4). The vast majority of patients with type 2 diabetes are obese. As obesity causes insulin resistance (5, 6), it is easy to understand why insulin resistance would be so commonly involved.There is mounting evidence (7–13) suggesting that the fundamental pathological sequence of events that leads to classic type 2 diabetes in most instances is the superimposition of obesity-related insulin resistance upon a β-cell with a genetically limited capacity to compensate. This view has recently received support from several studies (8, 13–15). In two of these (8, 13), it was found that when matched for obesity, normal glucose-tolerant, first degree relatives of patients with type 2 diabetes had impaired insulin secretion, but were not insulin resistant.