Reduced metal ion concentrations in atherosclerotic plaques from subjects with Type 2 diabetes mellitus

AimsTransition metal ions have been implicated in atherosclerosis. The goal of this study was to investigate whether metal ion levels were higher in people with diabetes, in view of their increased risk of aggravated atherosclerosis.Methods and resultsAbsolute concentrations of iron, copper, zinc and calcium, and products of protein and lipid oxidation were quantified in atherosclerotic lesions from subjects with (T2DM, n = 27), without Type 2 diabetes (nonDM, n = 22), or hyperglycaemia (HG, n = 17). Iron (P < 0.05), zinc (P < 0.01) and calcium (P = 0.01) were lower in T2DM compared to nonDM subjects. Copper levels were comparable. A strong correlation (r = 0.618; P < 0.001) between EPR-detectable and total iron in nonDM patients was not seen in T2DM. X-ray fluorescence microscopy revealed “hot spots” of iron in both T2DM and nonDM. Calcium and zinc co-localised and levels correlated strongly. F2-isoprostanes (P < 0.05) and di-Tyr/Tyr ratio (P < 0.025), oxidative damage markers were decreased in T2DM compared to nonDM, or HG.ConclusionAdvanced atherosclerotic lesions from T2DM subjects unexpectedly contained lower levels of transition metal ions, and protein and lipid oxidation products, compared to nonDM and HG. These data do not support the hypothesis that elevated metal ion levels may be a major causative factor in the aggravated atherosclerosis observed in T2DM patients.

► Elevated levels of metal ions have been proposed as catalysts in atherosclerosis. ► Lesions from people with and without Type 2 diabetes were analysed for metal ions. ► Levels of lipid and protein oxidation products were quantified. ► Lower levels of iron were detected in subjects with Type 2 diabetes than without. ► The data do not support a role for metal ions in diabetes-enhanced atherosclerosis.