DEFECTIVE PLASMA ANTIOXIDANT DEFENSES AND ENHANCED SUSCEPTIBILITY TO LIPID-PEROXIDATION IN UNCOMPLICATED IDDM

Oxidative stress is postulated to be increased in patients with IDDM. Accumulating evidence suggests that oxidative cell injury caused by fr ee radicals contributes to the development of IDDM complications. On t he other side, a decreased efficiency of antioxidant defenses (both en zymatic and nonenzymatic) seems to correlate with the severity of path ological tissue changes in IDDM. Thus, we determined plasma antioxidan t 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 subje cts. Compared with control subjects, IDDM patients showed significantl y reduced plasma TRAP (669 +/- 131 vs. 955 +/- 104 mu mol/l, P < 0.001 ) and significantly increased levels of ROOHs (7.13 +/- 2.11 vs. 2.10 +/- 0.71 mu mol/l, 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 ci s-trans conformation (0.0028 +/- 0.0011 vs. 0.0069 +/- 0.0012 AU, P < 0.001). The oxidative parameters studied did not appear to be correlat ed with metabolic control (HbA(1c) levels) and lipid profile (choleste rol or triglyceride levels). The reduced TRAP and the increased ROOH a nd conjugated diene plasma levels, together with the decreased ratio o f cis-trans/trans-trans conjugated dienes, which reflects an altered r edox status of plasma, indicate that in IDDM patients, oxidative stres s is enhanced and antioxidant defenses are defective, regardless of di abetes duration, metabolic control, or presence of complications.