Glucosepane and oxidative markers in skin collagen correlate with intima media thickness and arterial stiffness in long-term type 1 diabetes

Abstract

AimsTo study intima media thickness (cIMT) and arterial stiffness in type 1 diabetes of long duration, and their associations with the collagen cross-linker glucosepane and inflammatory and oxidative markers. MethodsTwenty-seven individuals with type 1 diabetes mellitus of 40years duration from the Oslo Study cohort and 24 age-matched controls were included. cIMT measurements of the carotid artery were performed longitudinally. Pulse wave velocity (PWV), augmentation index (AIx) and augmentation pressure (AP) were assessed cross-sectionally. Glucosepane and the oxidative product methionine sulfoxide (MetSO) were determined in skin collagen by liquid chromatography–mass spectrometry. Circulating inflammatory markers were determined by ELISAs. ResultsThe diabetes patients had significantly increased cIMT and arterial stiffness compared to controls. Significant correlations were noted for skin glucosepane with cIMT (r=0.41) and PWV (r=0.44). Skin MetSO and monocyte chemoattractant protein-1 (MCP-1) correlated significantly with AIx and AP. After correcting for age and mean arterial pressure in multiple linear regression analysis, MetSO and MCP-1 were both independently associated with AIx and AP. ConclusionsThese results suggest more premature atherosclerosis and arterial pathology in individuals with diabetes compared to age-matched controls. They also suggest an association between the arterial pathology and markers of collagen crosslinking, oxidative damage and inflammation in type 1 diabetes patients of forty years disease duration.