Link between glycation and lipoxidation in red blood cells in diabetes.
Oxidative stress is postulated to be increased in patients with diabetes mellitus. Glycation enhanced by elevated glucose concentrations may induce the formation of oxygen-derived free radicals (OFRs). OFRs would cause oxidative damage to endogenous molecules, including cholesterol. Accumulating evidence suggests that oxidative cell injury caused by OFRs contributes to the development of both macroangiopathy and microangiopathy in diabetes. Our previous studies have shown that 7-keto cholestadien is one of the major products of cholesterol peroxidation in diabetic erythrocyte membrane and its levels correlate with hemoglobin Alc (HbAlc) values. We have newly identified 3-cholesten-6-one, one of the minor products of cholesterol peroxidation, in it. The aim of our study is to investigate whether 3-cholesten-6-one levels also correlate with HbAlc values. Levels of 3-cholesten-6-one were assessed in erythrocyte membrane lipid by monitoring peak areas of 3-cholesten-6-one to cholesterol with gas chromatography-mass spectrometry. The peak area ratio of 3-cholesten-6-one to cholesterol was used as a marker of cholesterol peroxidation. The HbAlc value, an index of both glycemic stress and glycation, was measured by high-performance liquid chromatography. In this study, we evaluated 33 diabetic and 29 healthy subjects, matched for age (59.3+/-14.5 vs. 57.3+/-13.7 years, mean+/-S.D.) and sex (15 males and 14 females vs. 16 males and 17 females). There were both significantly raised HbAlc levels (4.6+/-0.8 vs. 8.3+/-2.4%, P<0.001) and significantly increased ratios of 3-cholesten-6-one to cholesterol (0.2+/-0.4 vs. 21+/-1.8, P<0.001) in diabetic patients compared to control subjects. A good correlation between HbAlc levels and ratios of 3-cholesten-6-one to cholesterol was found in participants (r = 0.75, P<0.001, y = 0.46x-1.8). This suggests that an oxidative stress exists in diabetes and the link between glycation and lipoxidation is found in diabetic red blood cell.
Inouye
M
M
Department of Internal Medicine, Hyogo Rehabilitation Center Hospital, Kobe, Japan.
Mio
T
T
Sumino
K
K
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008055:Lipids