Review: Hyperglycaemia and the vascular glycocalyx: the key to microalbuminuria and cardiovascular disease in diabetes mellitus?

Abstract

The vascular glycocalyx is a gel layer between endothelium and the blood, 0.5 µm thick. Evidence is presented from published studies to indicate that hyperglycaemia causes damage to the vascular glycocalyx. This damage results in microalbuminuria, excess fluid transfer to the interstitium, reduction in nitric oxide (NO) production by arterial endothelium, and leukocyte and platelet adhesion to endothelium leading to atherothrombosis. The lack of NO production proceeds from the fact that glycocalyx is the mechanotransducer transmitting the signal for increased shear stress between blood and arterial wall, and this function is inhibited by hyperglycaemia. When hyperinsulinaemia is also present, the problem is compounded by general arterial dilatation leading to low shear rates throughout the arterial tree. These findings explain the predisposition to atherothrombosis in the pre-diabetic condition of insulin resistance/metabolic syndrome/obesity and diabetes mellitus. It is proposed that greater efforts than ever are required to detect occult insulin resistance, to treat such patients and diabetics with ever more strict blood glucose control while minimising insulin levels, and to carry out further research into how glycocalyx structure and function can be preserved.