Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes

Insulin resistance is a characteristic feature of type 2 diabetes and plays a major role in the pathogenesis of the disease (1,2). Although �-cell failure is the sine qua non for development of type 2 diabetes, skeletal muscle insulin resistance is considered to be the initiating or primary defect that is evident decades before �-cell failure and overt hyperglycemia develops (3,4). Insulin resistance is defined as a reduced response of target tissues (compared with subjects with normal glucose tolerance [NGT] without a family history of diabetes), such as the skeletal muscle, liver, and adipocytes, to