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

Abstract

T he 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 prediabetic 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. Br J Diabetes Vasc Dis 2010;10:66-70

Update on the Important New Drug Target in Cardiovascular Medicine – the Vascular Glycocalyx

“…Damage by sepsis to glomerular glycocalyx causes breakdown of the glomerular filtration barrier and albuminuria [39] in conformity to our postulate of glycocalyx damage as the cause of microalbuminuria in diabetes mellitus [35]. A similar opinion is expressed by Salmon & Satchell [40] as "Generalised damage to the endothelial glycocalyx can manifest as both albuminuria and increased systemic microvascular permeability.…”

“…As such inhibition is thought to be the first step in the atherothrombotic disease process [34,35], some restoration of nitric oxide synthesis by insulin and metformin may be one mechanism by which these drugs retard progression of cardiovascular disease in both types of diabetes mellitus.…”

Vascular Fragility and the Endothelial Glycocalyx in the Tissues Lining the Healthy Gingival Crevice

“…In this model the flow, and hence diameter, in the venules in healthy tissues would adjust to maintain a constant venular hemoglobin oxygen saturation; changes in the supply to the tissues through dilation of the arterioles would be mediated by the increased shear stress causing dilation of the arterioles to maintain a constant wall shear stress (a dilated arteriole increases flow and reduces wall shear stress). The controlling step in this model is the venular hemoglobin oxygen saturation, mediated by increased or decreased flow in the venule 44 …”

Development of the damaged glycocalyx hypothesis - A review

“…The effect of diabetes mellitus has been the most explored of these conditions, in which endothelial glycocalyx damage coincides with microalbinuria in type 1 diabetes [22][23][24]. The loss of glycocalyx during hyperglycaemia can cause intravascular coagulation [25].…”