Oxidative Stress and Antioxidant Defense in Relation to the Severity of Diabetic Polyneuropathy and Cardiovascular Autonomic Neuropathy

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OBJECTIVEOxidative stress resulting from enhanced free-radical formation and/or a defect in antioxidant defenses has been implicated in the pathogenesis of experimental diabetic neuropathy. The objective of this study was to evaluate plasma levels of various biomarkers of oxidative stress in diabetic subjects in relation to the presence or absence of polyneuropathy (PN) and/or cardiovascular autonomic neuropathy (CAN).RESEARCH DESIGN AND METHODSPlasma 8-iso-prostaglandin F (8-iso-PGF), superoxide anion (O2•−) generation, lag phase to peroxidation by peroxynitrite (ONOO), vitamin E-to-lipid ratio, and vitamin C were measured in nonsmoking diabetic patients without PN and CAN (PN/CAN group; n = 62), in a group with PN but without CAN (PN+/CAN group; n = 105), in those with both PN and CAN (PN+/CAN+ group; n = 22), and in healthy control subjects (n = 85).RESULTSAll three markers of oxidative stress were significantly increased, and both markers of antioxidant defense were decreased in the PN+/CAN group compared with the control group (all P < 0.05). PN/CAN subjects showed a significant increase compared with control subjects for 8-iso-PGF, O2•−, and ONOO and a decrease for the vitamin E-to-lipid ratio (all P < 0.05). In the PN+/CAN group, a significant increase compared with the PN/CAN group was noted for O2•−, whereas the vitamin E-to-lipid ratio and vitamin C were reduced (all P < 0.05). No significant differences were noted between the PN+/CAN and PN+/CAN+ groups for each of the five markers of oxidative stress. In multivariate models, O2•− and ONOO were independently associated with neuropathic deficits, but diabetes duration and triglyceride levels were also independent determinants.CONCLUSIONSOxidative stress is enhanced in diabetic patients before the development of PN but to an even higher degree in those with PN, without further significant increase in relation to superimposed autonomic neuropathy. However, apart from oxidative stress, diabetes duration and triglyceride levels are also related to the severity of PN.

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