RELATIONSHIPS BETWEEN PLASMA MEASURES OF OXIDATIVE STRESS AND METABOLIC CONTROL IN NIDDM

Diabetes mellitus may be associated with increased lipid peroxidation which may contribute to long-term tissue damage. To test this hypothes is, we measured hydroperoxides (ROOHs) as well as alpha-tocopherol in plasma from healthy subjects and individuals with non-insulin-dependen t diabetes mellitus (NIDDM) (n=41 and 87, respectively). ROOHs were an alysed using the ferrous oxidation with xylenol orange version II (FOX 2) assay in conjunction with a specific ROOH reductant, triphenylphosp hine. alpha-Tocopherol was analysed by HPLC with fluorimetric detectio n. NIDDM patients had lower cholesterol standardised alpha-tocopherol levels as compared to control subjects (3.3+/-1.0 vs 5.1+/-2.3 (mu mol /l)/(mmol/l); p < 0.0005, Mann-Whitney test): range (1.5-6.5 vs 1.9-13 .0, respectively). Plasma ROOHs were substantially higher in the diabe tic subjects compared to those of the control subjects (9.4+/-3.3 vs 4 .1+/-2.2 mu mol/l; p < 0.0005 Mann-Whitney test: range 2.7-16.8 vs 0.4 -10.3, respectively). ROOH/cholesterol standardised alpha-tocopherol r atio was significantly higher in the diabetic patients compared to con trol subjects (3.2+/-1.6 vs 0.9+/-0.6; p < 0.0005, Mann-Whitney test: range 0.7-8.3 and 0.1-2.7, respectively). Plasma levels of ROOHs and a lpha-tocopherol were similar in diabetic patients with or without comp lications as well as in smokers and non-smokers. The present study con firms previous findings from this laboratory that NIDDM is associated with increased oxidative stress as assessed by plasma ROOHs. Increased oxidative stress in diabetic patients appears to be related to the un derlying metabolic abnormalities in diabetes, rather than to the compl ications of this disease. We therefore suggest that oxidative stress i s an early stage in the disease pathology which may contribute to the development of complications.