Diabetes Research Today is a free monthly online journal that collates and summarizes the latest research about Diabetes, including details on insulin, type i, type ii, diet, treatment, prevention.

Diabetes mellitus and macrovascular disease: mechanisms and mediators.

Boyle PJ

Department of Medicine, University of New Mexico, Albuquerque, New Mexico 87131-0001, USA. pboyle@salud.unm.edu

Atherosclerosis is a chronic inflammatory condition initiated in the endothelium in response to injury and maintained through the interactions between modified lipoproteins, macrophages, and arterial wall constituents. Risk for macrovascular disease is substantially increased in patients with type 2 diabetes mellitus. Factors underlying the link between insulin resistance/type 2 diabetes and macrovascular disease include reduced adiponectin concentration, increased expression of vascular cell adhesion molecule-1 and consequent adhesion of T-lymphocytes to the coronary endothelium, procoagulability with increased expression of plasminogen activator inhibitor-1 (PAI)-1, and instability of atherosclerotic plaques resulting from increased expression by macrophages of matrix metalloproteinases (MMPs). Thiazolidinediones (TZDs) are agonists of peroxisome proliferator-activated receptor (PPAR)-gamma and increase adiponectin. TZD therapy is associated with decreases in hepatic fat content and glycosylated hemoglobin and an increase in hepatic glucose disposal. TZDs lower circulating free fatty acid concentration and triglyceride content in the liver, but not in skeletal muscle. Effects of PPAR-gamma agonists in vitro and in animal models provide evidence for additional potential antiatherosclerotic benefits in patients with diabetes beyond the treatment of hyperglycemia and dyslipidemia, including the reduction of expression of macrophage MMPs and scavenger receptor-1, and indirect reduction of PAI-1 and inhibition of vascular smooth muscle cell proliferation, via suppression of type 1 angiotensin-2 receptor expression. Dual PPAR-alpha/gamma agonists, retinoid receptor agonists, and, to a lesser extent, TZDs, also stimulate cholesterol efflux from macrophages in vitro.

Published 10 September 2007 in Am J Med, 120(9): S12-7.
Full-text of this article is available online (may require subscription).

© 2004-2008 Diabetes Research Today. All Rights Reserved.