Link between glycation and lipoxidation in red blood cells in diabetes

Oxidative stress is postulated to be increased in patients with diabetes me llitus. Gycation enhanced by elevated glucose concentrations may induce the formation of oxygen-derived free radicals (OFRs). OFRs would cause oxidati ve damage to endogenous molecules, including cholesterol. Accumulating evid ence suggests that oxidative cell injury caused by OFRs contributes to the development of both macroangiopathy and microangiopathy in diabetes. Our pr evious studies have shown that 7-keto cholestadien is one of the major prod ucts of cholesterol peroxidation in diabetic erythrocyte membrane and its l evels correlate with hemoglobin Ale (HbAlc) values. We have newly identifie d 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 le vels also correlate with HbAlc values. Levels of 3-cholesten-6-one were ass essed in erythrocyte membrane lipid by monitoring peak areas of 3-cholesten -6-one to cholesterol with gas chromatography-mass spectrometry. The peak a rea ratio of 3-cholesten-6-one to cholesterol was used as a marker of chole sterol 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 (5 9.3+/-14.5 vs. 57.3+/-13.7 years, mean+/-S.D.) and sex (15 males and 14 fem ales vs. 16 males and 17 females). There were both significantly raised HbA lc levels (4.6+/-0.8 vs. 8.3+/-2.4%, P<0.001) and significantly increased r atios of 3-cholesten-6-one to cholesterol (0.2+/-0.4 vs. 21+/-1.8, P < 0.00 1) in diabetic patients compared to control subjects. A good correlation be tween HbAlc levels and ratios of 3-cholesten-6-one to cholesterol was found in participants (r = 0. 75, P < 0.00 1, y = 0.46x - 1.8). This suggests th at an oxidative stress exists in diabetes and the link between glycation an d lipoxidation is found in diabetic red blood cell. (C) 1999 Elsevier Scien ce B.V. All rights reserved.