Microvascular Function in Type 2 Diabetes

Background: Microvascular dysfunction underlies many of the debilitating complications associated with type 2 diabetes (T2DM), yet their development and progression remains poorly understood. Traditional assessments of capillary microscopy have detected few abnormalities beyond morphological changes, and the impact of endothelial glycocalyx (EG) loss on microvascular function in vivo is unclear. Aims: This study aimed to (1) assess EG integrity (via perfused boundary region [PBR]) in individuals with T2DM, with and without microalbuminuria, compared to controls; (2) examine associations between EG integrity and established measures of microvascular function; and (3) evaluate capillaroscopic parameters in the hands and feet of T2DM participants versus controls. Methods: Non-invasive microvascular imaging was performed in a total of 408 participants, recruited across two clinical trials. Techniques included capillary microscopy (density, flow volume and velocity, spacing heterogeneity). Measurement of maximum and peak reactive hyperaemia, iontophoresis of acetylcholine and sodium nitroprusside (endothelial dependent and independent vasodilation), and sublingual microscopy for estimation of EG integrity. Results: T2DM participants exhibited capillary rarefaction in the hand, accompanied by increased domain area and spacing heterogeneity, without differences in flow velocity or volume. Maximum hyperaemia was impaired in T2DM participants with microalbuminuria, while reactive hyperaemia and endothelial (in)dependent vasodilation responses were unchanged. Loss of EG integrity correlated with reduced maximum hyperaemia in T2DM participants; however, there was no evidence that EG loss was more prevalent in T2DM, or T2DM+MA groups compared to controls. Conclusion: This study highlights microvascular structural and functional abnormalities in T2DM. While EG disruption was linked to impaired MH, no greater EG loss was observed in T2DM. These findings partially support the role of EG dysfunction in microvascular impairment and identify areas for further investigation.