The effect of varıabılıty blood glucose levels on plasma and urıne oxıdatıon ın patıent wıth type 2 dıabetes

The aim of this study was to evaluate the effect of high dose insulin analog initiation therapy on glucose variability and oxidative stress in type 2 diabetes patients. Twenty four type 2 diabetic patients with HbA1c levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs such as, 0.4 U/kg/day lispro mix (50% insulin lispro protamine and 50% insulin lispro) (n=8); 0.4 U/kg/day insulin aspart (30% insulin aspart and 70% protamine insulin aspart) (n=8) and 0.4 U/kg/day insulin glargine (n=8). Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood/urine samples were obtained from all patients at 24 and 72 hours. Plasma 8-isoprostane, protein carbonyl and nitrotyrosine levels were measured to evaluate oxidized lipids, oxidized and nitrated proteins, respectively. Plasma nitrite and nitrate levels were also determined to assess nitric oxide (NO) production in all experimental groups. The glucose patterns obtained from each patient on study days 1 and 3 were submitted to calculations and showed that overall glucose control was significantly better following treatment with insulin analog plus metformin compared to sulphonylurea and metformin alone. Treatment with insulin analog plus metformin also resulted in a significant reduction in glucose variability, as determined by decreased standard deviation of measured blood glucose concentrations. Plasma and urine 8-isoprostane, plasma protein carbonyl and nitrotyrosine levels were markedly decreased following treatment with insulin analog plus metformin. No significant difference was observed in plasma nitrite and nitrate values suggesting similar levels of NO production. These findings indicate that lowering blood glucose and glucose fluctuations using high dose insulin analogs plus metformin reduces oxidative stress over time. The present data also suggest that therapy in type 2 diabetes should also target the reduction of acute glucose fluctuations as well as hemoglobin A1c and mean glucose concentrations.