Antioxidative effects of probucol in complex therapy for type 2 diabetes

By taking into account the role of lipid peroxides in the development of atherosclerosis, the authors studied the time course of changes in the content of primary oxidized low-density lipoproteins (oxy-LDL) and secondary (malonic dialdehyde (MDA)) lipid peroxidation (LPO) products in LDL and the activity of antioxidative (АО) defense enzymes in 30 patients with type 2 diabetes mellitus (DM-2) before and during achieved compensation of carbohydrate metabolism, thereafter the patients were randomized to either a group receiving the antioxidant probucol in a daily dose of 1.0 g (n = 20) or a control group taking no antioxidant therapy (n = 10). With compensated carbohydrate metabolism, plasma LDL showed 30 and 40% reductions in oxy-LDL and MDA, respectively, and 2.2 and 1.3-fold increases in the activity of АО defense enzymes (superoxide dismutase and glutathione peroxidase), respectively. In the probucol group, there were a decrease in LDL oxygen demand by 77% of the baseline value and 45 and 6S% reductions in the LDL levels of oxy-LDL and MDA, respectively; such changes were not revealed in the control group. With administration of probucol, there was a drop in the HOMA-IR and 1SI indices, which directly correlated with the lower plasma LDL levels of oxy-LDL (r = 0.454; p < 0.05) and MDA (r = 0.549; p < 0.05). With the use of probucol, there was a rise in stimulated insulin secretion, which inversely correlated with the decreases in oxy-LDL (r = -0.4S9; p < 0.01) and MDA (r = -0.44; p < 0.05). The findings suggest that inclusion of the antioxidant probucol into the complex therapy for DM-2 not only reduces the risk of progressive atherosclerosis, but also results in diminished insulin resistance and increased secretory capabilities of betta-cells, facilitating better glycemic control.

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