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 micromol/l, P < 0.001) and significantly increased levels of ROOHs (7.13 +/- 2.11 vs. 2.10 +/- 0.71 micromol/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 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 (HbA1c 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.

Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes

“…The limited number of smokers might explain why our results on smoking are not in accordance with earlier reports on the association between smoking and elevated urinary excretion of 8-isoprostanes [17,18,26]. An explanation for the lack of correlation between glucose variability and oxidative stress may be that, unlike patients with type 2 diabetes, patients with type 1 diabetes are not sensitive to glucose variability as a stimulator of oxidative stress, because of different underlying pathophysiological mechanisms [28,[32][33][34][35]. The significantly higher excretion of 15 S ð Þ-8-iso-PGF 2α in patients with type 1 diabetes as compared with healthy controls does suggest the existence of a factor favouring oxidative stress.…”

Tyrosine Nitration of Prostacyclin Synthase Is Associated with Enhanced Retinal Cell Apoptosis in Diabetes

“…Oxidized LDL-mediated inflammation and vascular damage are critical in the pathogenesis of atherosclerosis as well as diabetic complications, [32][33][34][35][36] including diabetic retinopathy, as witnessed by our own studies. Diabetes may amplify LDL oxidation and exacerbate its complications by increasing glycation of plasma LDL 37 and rendering the lipoprotein more susceptible to oxidation.…”

Glycemic index in chronic disease: a review

“…Endothelium-dependent vasodilation impaired by dietary glucose ingestion seemed to be restored by consumption of antioxidant vitamins (Levine et al, 1996;Title et al, 2000;Skyrme-Jones et al, 2000). Diabetic patients (type 1 and 2) tend to be more prone to endothelial dysfunction (eg decreased endothelium-dependent vasodilation) and to have higher levels of oxidative stress than healthy populations (Clarkson et al, 1996;Williams et al, 1996;Akkus et al, 1996;Santini et al, 1997;Ceriello et al, 1998b) and in healthy individuals postprandial hyperglycemia appears to result in increased oxidative stress (Koska et al, 1997;Ceriello et al, 1998a;Kawano et al, 1999).…”