Lipid-derived modifications of plasma proteins in experimental and human diabetes

Plasma from two diabetic rat models and human diabetic patients was analyzed to investigate the hypothesis that enhanced oxidative stress in diabetes promotes lipid-derived protein modification. We evaluated the nonenzymatic modification of plasma protein by oxidized phospholipids, including measurement of protein-bound pentanedioate, nonanedioate, and hexanoate, all derived from oxidation of phospholipid polyunsaturated fatty acids. Generally pentanedioate was higher in diabetic compared with nondiabetic control groups, and nonanedioate was also higher in the diabetic rat models. We conclude that diabetes is associated with higher levels of phospholipid-derived protein modification in both animal models and human diabetes. Their role in the development of diabetes vascular complications warrants further research.