The pathologic continuum of diabetic vascular disease

Abstract

Hyperglycemia can promote vascular complications by multiple mechanisms, with formation of advanced glycation end products and increased oxidative stress proposed to contribute to both macrovascular and microvascular complications. Many of the earliest pathologic responses to hyperglycemia are manifest in the vascular cells that directly encounter elevated blood glucose levels. In the macrovasculature, these include endothelial cells and vascular smooth muscle cells. In the microvasculature, these include endothelial cells, pericytes (in retinopathy), and podocytes (in renal disease). Additionally, neovascularization arising from the vasa vasorum may promote atherosclerotic plaque progression and contribute to plaque rupture, thereby interconnecting macroangiopathy and microangiopathy.

Fig. 1. Intersection of Microangiopathy and Macroangiopathy in Accelerated Atherosclerosis

In type 2 diabetes, both angiogenesis and microangiopathy are increased and may contribute to accelerated atherosclerosis and the development of vulnerable plaque. Hyperglycemia is a driving force in both large and small vessel disease. Indeed, the two disorders may be interconnected, with microvascular disease promoting atherosclerosis through processes such as hypoxia and changes in the vasa vasorum.