Defective Plasma Antioxidant Defenses and Enhanced Susceptibility to Lipid Peroxidation in Uncomplicated IDDM

Abstract

Oxidative stress is postulated to be increased in patients with IDDM. Accumulating evidence suggests that oxidative cell injury caused by free radicals contributes to the development of IDDM complications. On the other side, a decreased efficiency of antioxidant defenses (both enzymatic and nonenzymatic) seems to correlate with the severity of pathological tissue changes in IDDM. Thus, we determined plasma antioxidant defenses, measuring the total radical-trapping antioxidant capacity (TRAP) and the two markers of oxidative stress, lipid hydroperoxides (ROOHs) and conjugated dienes, in 72 patients with well-controlled IDDM and without evident complications, compared with 45 nondiabetic subjects. Compared with control subjects, IDDM patients showed significantly reduced plasma TRAP (669 ±131 vs. 955 ± 104 μmol/1, P < 0.001) and significantly increased levels of ROOHs (7.13 ± 2.11 vs. 2.10 ± 0.71 μmol/1, P < 0.001) and conjugated dienes (0.0368 ± 0.0027 vs. 0.0328 ± 0.0023 arbitrary units [AU], P < 0.01), especially in the trans-trans conformation (0.0340 ± 0.0028 vs. 0.0259 ± 0.0022 AU, P < 0.001), with a concurrent reduction of conjugated dienes in the cis-trans conformation (0.0028 ± 0.0011 vs. 0.0069 ± 0.0012 AU, P < 0.001). The oxidative parameters studied did not appear to be correlated with metabolic control (HbA_1c levels) and lipid profile (cholesterol or triglyceride levels). The reduced TRAP and the increased ROOH and conjugated diene plasma levels, together with the decreased ratio of cis-trans/trans-trans conjugated dienes, which reflects an altered redox status of plasma, indicate that in IDDM patients, oxidative stress is enhanced and antioxidant defenses are defective, regardless of diabetes duration, metabolic control, or presence of complications.