Insulin is the most important hormone in regulating fuel metabolism. If there is a defect in either insulin secretion or insulin action, this can cause major metabolic abnormalities/l/. For example, autoimmune destruction of the ß-cell leads to type 1 diabetes mellitus, a disease characterized by hyperglycemia and ketoacidosis. In contrast, type 2 diabetes mellitus is generally associated with two physiologic defects: insulin deficiency and insulin resistance 121. Although the molecular causes of the common forms of type 2 diabetes have not yet been elucidated, specific molecular defects have been identified in some patients with relatively uncommon variants of noninsulin-dependent diabetes mellitus-eg, maturity-onset diabetes of the young (MODY) and genetic syndromes associated with insulin resistant diabetes. This paper focuses on patients with insulin resistance due to mutations in the insulin receptor gene.