Targeting insulin resistance and beta-cell dysfunction: the role of thiazolidinediones.
Insulin resistance and beta-cell dysfunction are fundamental defects that contribute to the development of type 2 diabetes, and as such are targets for primary prevention of disease progression. The two parameters are linked by several factors, including glucotoxicity and lipotoxicity, and recent research has enlightened understanding of the molecular mechanisms underlying the development and progression of the disease. Historically, type 2 diabetes has been managed by controlling hyperglycemia, using agents that increase insulin levels or reduce hepatic glucose production, as exemplified by the United Kingdom Prospective Diabetes Study. The thiazolidinediones control hyperglycemia by targeting the fundamental defects of the disease, and have shown well-documented improvements in insulin sensitivity and beta-cell function, both in monotherapy and in combination with other oral antidiabetic agents. TRoglitazone In the Prevention Of Diabetes (TRIPOD) has demonstrated the potential for thiazolidinediones to delay progression to type 2 diabetes. Prospective studies such as Diabetes REduction Approaches with ramipril and rosiglitazone Medications (DREAM) are currently evaluating the long-term effects of thiazolidinediones on metabolic status and disease progression.
Del Prato
S
S
Section of Diabetes and Metabolic Diseases, Department of Endocrinology and Metabolism, Ospedale Cisanello, Pisa, Italy. delprato@immr.med.unipi.it
Marchetti
P
P
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D018450:Disease Progression; D005230:Fatty Acids, Nonesterified / Q000097:blood; D018149:Glucose Intolerance; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D045162:Thiazolidinediones / Q000627:therapeutic use*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones