Thiazolidinediones and vascular damage.
OBJECTIVE
Although the thiazolidinediones were introduced for the treatment of hyperglycemia in type 2 diabetes, it became quickly apparent that these agents modulated many pathways related to vascular physiology and pathophysiology. Given the fact that cardiovascular disease is the leading cause of death in diabetes, it has become important to know whether these agents have vasculoprotective effects and if so whether these are associated with the prevention of cardiovascular disease.


RESULTS
The thiazolidinedione class improves endothelial vasomotion, inhibits inflammatory and procoagulant processes and has powerful antiproliferative and antioxidant effects. Experimentally these agents retard atherosclerosis development in predisposed animals. Clinical studies demonstrate that they increase HDL cholesterol and LDL size, and may lower triglyceride levels. They modestly lower blood pressure, reduce microalbuminuria, arterial stiffness and reduce carotid wall thickening. These effects are generally independent of glucose lowering and in many instances have been shown to occur in nondiabetic subjects. A single clinical endpoint intervention trial of add-on pioglitazone treatment in type 2 diabetic patients with cardiovascular disease suggested on secondary analyses that the agent reduced cardiovascular events.


CONCLUSIONS
The weight of the experimental, subclinical and clinical assessments of the effects of these agents supports the contention that they are vasculoprotective. In the final analysis their use in clinical practice to prevent cardiovascular disease will mostly depend on whether clinical trials consistently demonstrate that they reduced cardiovascular events.
Goldberg
Ronald B
RB
Division of Endocrinology, Diabetes and Metabolism, Diabetes Research Institute, The University of Miami Miller School of Medicine, Miami, Florida 33136, USA. rgoldber@med.miami.edu
D001808:Blood Vessels / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D019610:Cytoprotection; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D045162:Thiazolidinediones / Q000627:therapeutic use*
D045162:Thiazolidinediones