Short-Term Insulin Therapy and Normoglycemia: Effects on erythrocyte lipid peroxidation in NIDDM patients

OBJECTIVE To evaluate erythrocyte lipid peroxidation (LPO) before and after an adaptive short-term insulin therapy in NIDDM patients who were chronically hyperglycemic.

RESEARCH DESIGN AND METHODS Twenty-six patients with NIDDM (mean HbA_1c, 11.28%) aged 53.04 ± 2.03 years were submitted for 3 days to constant intravenous glucose and continuous insulin perfusion at an adaptable rate to maintain glycemia within the normal range. An evaluation of LPO at baseline and after euglycemic insulin therapy was determined by erythrocyte free and total malondialdehyde (MDA) levels, polyunsaturated fatty acid (PUFA) percentage, vitamin E and glutathione content, and the following antioxidant enzymatic activity determinations: glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). Fasting serum glucose, HbA_1c, triglycerides, cholesterol, and HDL cholesterol levels were also determined 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] for free MDA; 18.04 ± 1.79 vs. 7.85 ± 0.55 nmol/g Hb [P < 0.0001] for 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% of total fatty acids, respectively). Vitamin E and glutathione were reduced significantly (6.16 ± 0.61 vs. 14.84 ± 0.64 nmol/g Hb and 0.42 ± 0.04 vs. 0.97 ± 0.06 mmol/l, respectively). No difference was observed for the enzymatic activities. After euglycemic insulin therapy, triglycerides significantly decreased compared with baseline concentrations (1.55 ± 0.13 vs. 2.42 ± 0.22 mmol/l; P < 0.001), whereas other lipidic parameters were unchanged. Free MDA significantly decreased (8.60 ± 0.76 vs. 11.14 ± 0.80 nmol/g Hb [P < 0.01]), while vitamin 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.

CONCLUSIONS The observed erythrocyte LPO in NIDDM decreased after a short-term adaptive insulin therapy. This decrease could be principally attributed to the normalized glycemia that reduces reactive oxygen species (ROS) production, which in turn may explain the increase in erythrocyte 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.