Modified lipoproteins in diabetes

The mechanisms by which diabetes leads to various manifestations of tissue damage are not yet fully understood; however, different recent studies suggest that some of them may be mediated by modified lipoproteins, although other lipid abnormalities also have been described in diabetes patients. Principally, the modification consists of an oxidation of the lipoprotein particle [mainly low-density lipoprotein (LDL)]. The oxidized LDL is then rapidly internalized by macrophages, converting them to cholesterol-loaded foam cells. In diabetic patients, oxidation occurs through two pathways: enzymatic (vascular inflammation) and nonenzymatic (polyunsaturated fatty acids) that can be blocked either by acetyl salicylic acid or by antioxidants. Moreover, in diabetes patients, higher glucose levels can also lead to a direct (stimulated by metals) or an indirect (by generation of glycosylated proteins) generation of free radicals, which will also damage proteins and collagen in particular. Clinically, lipid peroxide concentrations are higher in diabetic than in nondiabetic subjects, particularly in patients with vascular complications and with high triglyceride levels. These lipid peroxide levels can be decreased by antioxidants, whose concentrations are lower in diabetic patients. Preliminary data also indicate that HMG CoA reductase inhibitors can decrease lipid peroxide concentrations.