Evaluacija uticaja terapije insulinskim analozima na parametre oksidativnog stresa kod bolesnika sa dijabetesom melitusom tip 1

Abstract

Significance of Type 1 diabetes mellitus is in it’s acute and chronic complications. Big studies demonstrated that microvascular complications of diabetes can be avoided or delayed if blood glucose levels are maintained as close to the normal range as possible. Diabetic state is closely related with increase in oxidative stress and studies suggest that ROS are important in pathogenesis of diabetic vascular dysfunction and that pathways of development of diabetic complications are closely connected with oxidative stress. High blood glucose leads to increase generation of ROS in mitochondria. Intensive insulin therapy is the cornerstone for tight glycemic control in type 1 diabetic patients. Basic difficulties in achieving glycemic goals are maintenance of near-euglycemia and avoidance of hypoglycemia and significant weight gain. Insulin analogues have improved pharmacokinetic properties that allow better control of both fasting and postprandial glycaemia. Aim of this work was to analyze efficacy of intensive insulin therapy with human insulin analogues (aspart and glargine) with analysis of glycoregulation (HbA1c, fasting blood glucose, postprandial glucose and glucose variability), safety with analysis of hypoglycemia, body weight and quality of life, and analysis of markers of oxidative stress. In this prospective clinical trial we analyzed clinical and laboratory parameters in Type 1 diabetic patients. Study included 49 patients with T1DM and previous therapy with human insulin for at least one year, currently on IIT with four daily doses of human insulin. For the first three months rapid acting insulin analogue (insulin aspart) was introduced instead of regular human insulin, and then in the next three months patients were treated with basal insulin analogue (insulin glargine) instead of intermediate acting human insulin. The mean HbA1c level fell after introduction of insulin analogues therapy. There was small but no significant decline in HbA1c level during 3 months of therapy with insulin aspart and HbA1c level continued to fall and after 3 month of therapy with combination of insulin analogues (aspart/glargine) was significantly lower than before initiation of therapy with analogues. There was significant decline in all postprandial glycaemia after three main vii meals during first 3 months of therapy. Blood glucose variability was significantly lower, as well as mean increment of blood glucose after the meals. At the end of the study all the values of blood glucose in glucose profiles were lower as well as mean blood glucose and glucose variability. Our results show significant reduction in the number of hypoglycemia after introduction of insulin analogues therapy. Number of all hypoglycemic episodes is lower after first three months of therapy and even more so after introduction of insulin glargine in the therapy. There were significant differences in the number of symptomatic, asymptomatic and night hypoglycemia. We recorded small, but significant weight loss and decline of the level of CRP. Our results show that in Type 1 diabetic patients level of oxidative stress (measured as MDA) is significantly higher than in control population. There was also significantly higher level of nitrates and nitrites in patients compared with control subjects, higher activity of XO, there was significantly lower activity of SOD and significantly higher activity of catalase and GPx. Level of MDA is significantly lower after therapy, as was the level of nitrates and nitrites and XO, there was a significant rise in activity of SOD and significant fall of activity of catalase and GPx. Intensive insulin therapy of Type 1 diabetic patients with insulin analogues (aspart and glargine) leads to better glycemic control with smaller number of hypoglycemic episodes and small weight loss. Intensive insulin therapy of Type 1 diabetic patients with insulin analogues (aspart and glargine) through improvement of glycemic control improves parameters of oxidative stress.