SHORT-TERM INSULIN THERAPY AND NORMOGLYCEMIA - EFFECTS ON ERYTHROCYTELIPID-PEROXIDATION IN NIDDM PATIENTS

OBJECTIVE - To evaluate erythrocyte lipid peroxidation (LPO) before an d after an adaptive short-term insulin therapy in NIDDM patients who w ere chronically hyperglycemic. RESEARCH DESIGN AND METHODS - Twenty-si x patients with NIDDM (mean HbA(1c), 11.28%) aged 53.04 +/- 2.03 years were submitted for 3 days to constant intravenous glucose and continu ous insulin perfusion at an adaptable rate to maintain glycemia within the normal range. An evaluation of LPO at baseline and after euglycem ic insulin therapy was determined by erythrocyte free and total malond ialdehyde (MDA) levels, polyunsaturated fatty acid (PUFA) percentage, vitamin E and glutathione content, and the following antioxidant enzym atic activity determinations: glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). Fasting serum glucose, HbA(1c), t riglycerides, cholesterol, and HDL cholesterol levels were also determ ined at these time points. RESULTS - At baseline, erythrocyte free and total MDA were significantly higher in NIDDM patients than in control subjects (11.14 +/- 0.80 vs. 1.74 +/- 0.11. nmol/g Hb [P < 0.0001] fo r free MDA; 18.04 +/- 1.79 vs. 7.85 +/- 0.55 nmol/g Hb [P < 0.0001] fo r total MDA). PUFAs, particularly C20:4 and C22:5, were increased (14. 69 +/- 0.34 vs. 12.03 +/- 0.31 and 2.31 +/- 0.04 vs. 1.71 +/- 0.03 % o f total fatty acids, respectively). Vitamin E and glutathione were red uced significantly (6.16 +/- 0.61 vs. 14.84 +/- 0.64 nmol/g Hb and 0.4 2 +/- 0.04 vs. 0.97 +/- 0.06 mmol/l, respectively). No difference was observed for the enzymatic activities. After euglycemic insulin therap y triglycerides significantly decreased compared with baseline concent rations (1.55 +/- 0.13 vs. 2.42 +/- 0.22 mmol/l; P < 0.001), whereas o ther lipidic parameters were unchanged. Free MDA significantly decreas ed (8.60 +/- 0.76 vs. 11.14 +/- 0.80 nmol/g Hb [P < 0.01]), while vita min E increased (7.93 +/- 0.73 vs. 6.16 +/- 0.61 nmol/g Hb [P < 0.05]) . No difference was observed for PUFAs, glutathione, or total MDA. CON CLUSIONS - The observed erythrocyte LPO in NIDDM decreased after a sho rt-term adaptive insulin therapy This decrease could be principally at tributed to the normalized glycemia that reduces reactive oxygen speci es (ROS) production, which in turn may explain the increase in erythro cyte membrane vitamin E and the decrease in MDA. This study shows the value of a euglycemic environment in NIDDM to reduce LPO and, at long range, to minimize clinical diabetes complications.