Advances in diabetes for the millennium: understanding insulin resistance.
Type 2 diabetes is a heterogeneous disorder in which both insulin resistance and impaired insulin secretion play important roles. Studies in monozygotic twins in which one is discordant for type 2 diabetes and studies of first-degree relatives of patients with type 2 diabetes who still have normal glucose tolerance indicate that impaired insulin secretion can be detected before insulin resistance, suggesting that impaired beta-cell function may be the primary genetic defect. The insulin resistance found in most individuals with impaired glucose tolerance and/or type 2 diabetes appears to be largely acquired and can be accounted for by obesity, physical inactivity, and glucose and lipotoxicity. Progressive deterioration in beta-cell function as demonstrated in the United Kingdom Prospective Diabetes Study (UKPDS) and/or worsening of insulin resistance leads to deterioration in glucose tolerance and to secondary failure of oral antidiabetic drugs. Therefore, agents that improve beta-cell function (such as sulfonylureas and meglitinides) and insulin sensitizers (such as metformin and thiazolidinediones) both are useful alone or in combination for treating type 2 diabetes.
Gerich
John E
JE
Clinical Research Center, University of Rochester School of Medicine, Rochester, New York, USA.
Dailey
George
G
D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells