Why does diabetes increase atherosclerosis? I don't know!

Abstract

There is a wealth of clinical data showing the relationship between diabetes mellitus and atherosclerosis and its clinical complications. To dissect this relationship, investigators have attempted, usually unsuccessfully, to create a small-animal model in which diabetes accelerates vascular lesion development. This effort has often been complicated by development of hyperlipidemia leading to difficulty in differentiating the effects of hyperglycemia from those of lipid abnormalities. A study in the current issue of the JCI provides data on a new mouse model in which atherosclerosis initiation is accelerated in diabetic mice and is reduced by insulin therapy. Moreover, these animals have greater intra-arterial hemorrhage, which might be due to less stable plaques.

Figure 1

Potential causes of diabetes-induced macrovascular disease. The presence of increased conventional risk factors in patients with diabetes is surely one reason for greater atherosclerosis (18). In some animal models, diabetes-induced hyperlipidemia occurs and may mask toxic effects of hyperglycemia that confer diabetes-specific risk. Among these effects may be the development of increased levels of AGEs, toxic intracellular reactions to glucose secondary to the production of increased reactive oxygen species (19), and multiple effects on the production of matrix proteins and the biology of cells within the vessel wall.