GLYCOXIDATION, AND PROTEIN AND DNA OXIDATION IN PATIENTS WITH DIABETES-MELLITUS

1. The role of oxidative stress in the pathogenesis of the diabetic st ate is being investigated extensively. Although oxidative stress has b een reported in terms of glycoxidation, protein oxidation and DNA oxid ation in diabetes mellitus, oxidation parameters have not been determi ned in parallel on the same study population. 2. We studied 24 patient s with diabetes mellitus (14 patients with Type I diabetes with a mean age of 62.3 +/- 6.3 years and IO patients with Type II diabetes aged 67.3 +/- 5.9 years) and compared them with age-matched non-diabetic co ntrols. Urinary o-tyrosine, 8-hydroxy-2'-deoxyguanosine and pentosidin e measurements by HPLC were made on two occasions (t1 and t2). 3. A cl ear statistical difference was found between diabetic patients and con trols at t1 or t2 for 8-hydroxy-2'-deoxyguanosine and pentosidine, but not for o-tyrosine. No significant correlations were found between cl inical and other laboratory parameters except high-density lipoprotein and uric acid. We revealed significantly increased glycoxidation and DNA oxidation in patients with Type I and Type ii diabetes, but protei n oxidation was not different from controls. 4. The finding of increas ed glycoxidation reflects increased oxidation of the carbohydrate moie ty, whereas the increased levels of oxidized DNA may also be interpret ed as due to increased DNA repair. The increased 8-hydroxy-2'-deoxygua nosine does not indicate the generation of an individual active oxygen species, but DNA could have been oxidized simply by alkenals from lip id peroxidation, as e.g. malondialdehyde. As no difference in protein oxidation (i.e. o-tyrosine) between diabetics and controls could be re vealed, the oxidation of DNA by hydroxyl radical attack is unlikely, a s o-tyrosine was proposed as a marker for hydroxyl radical attack. The refore, the message is that increased glycoxidation can be confirmed, protein oxidation does not appear to take place and increased DNA oxid ation is still not proven, as increased 8-hydroxy-2'-deoxyguanosine ma y simply reflect repair.