Glycated hemoglobin and lipid peroxidation in erythrocytes of diabetic patients

In diabetes, glycation and subsequent browning (or glycoxidation) reactions are enhanced by elevated glucose concentrations. It is unclear whether the diabetic state per se also induces an increase in the generation of oxygen-derived free radicals (OFRs). However, there is some evidence that glycation itself may induce the formation of OFRs. OFRs cause oxidative damage to endogenous molecules, including cholesterol. 7-Oxocholesterol is known to be one of the major products of cholesterol oxidation. The level of cholesterol peroxidation products was assessed in erythrocyte membrane lipid by monitoring the peak height ratio of 7-oxocholesterol, one of the products of cholesterol peroxidation, to cholesterol with gas chromatography/mass spectrometry (GC/MS). The peak height ratio of 7-oxocholesterol to cholesterol was used as a biomarker of lipid peroxidation. The hemoglobin A1c (HbA1c) value, an index of glycemic stress, was measured by high-performance liquid chromatography. We examined the relationship between the levels of cholesterol peroxidation products and HbA1c in erythrocytes of diabetic and healthy subjects. There was a significantly increased ratio of 7-oxocholesterol to cholesterol in diabetic erythrocytes compared with control erythrocytes. The ratio of 7-oxocholesterol to cholesterol was significantly correlated with the level of HbA1c. This suggests that glycation of hemoglobin via chronic hyperglycemia is linked to cholesterol peroxidation in erythrocytes of both diabetic and healthy subjects.