The Relationship Between Oxidative Stress And Diabetes Due To MtDNA Mutation & Complication Of Type 2 Diabetes

Objective: Diabetes mellitus has became a serious social problem.The oxidative stress is closely related to the development of diabetes.Mutation of mtDNA contributes to the dysfunction of the synthesis of ATP and respitary train,which aggravated the oxidative stress in the mitochondrial.There is a probable relationship between the oxidative stress and the unique clinical characters of mitochondrial diabetes.In this study,the level of markers of oxidative stress in periperical blood and ATP in erythrocyte was determined in mtDM, T2DM and healthy controls.Discuss the relationship between oxidative stress and mtDNA mutation.Moreover, evalue the effect of oxidative stress on some characteristics of diabetes and diabetic complications.Methods: 16 diabetes with mitochondrial DNA mutation was recruited, who was diagnosed through directly sequencing of PCR production and was divided into two subgroup:A3243G mutation subgroup and A12026G mutation subgroup.At the same time,64 type 2 diabetes and 32 non-diabetes healthy subject were randomly recruited,who were matched with mtDM group in the sex and age without any mtDNA mutation mentioned above.The clinical biochemical index were collected.Total genome was extracted conventionally in peripheral leucocytes from patients of T2DM and Normal in order to exclude the mutation carriers.Venous blood was drew from all the participants of the three groups in which the activity of SOD, GSH-Px, CAT and anti-ROS and the level of MDA were determined by the special kits,the level of ATP, ADP, AMP in erythrocyte were measured by HPLC.The situation of oxidative stress and level of ATP between the three group were compared with correct statistic method.Analyse the relationship between the oxidative stress and mtDNA mutation, genesis of diabetes and its complication.Results:1.In mtDM group ,decreased activity of SOD, GSH-Px, CAT, anti-ROS and increased level of MDA are found in comparison with normal group.Decreasedactivity of CAT and increased level of MDA are found in mtDM group compared with T2DM group.In the T2DM group,compared with Normal group,there is decreased activity of anti-oxidase and increased level of MDA.In the mtDM group,between the two subgroup A3243G and A12026G,the agravated tendency without statistic difference is found in the former.2.The content of ATP and ATP/ADP in erythrocyte was dramatically dereased and that of AMP is increased in the mtDM group compared with the normal group.The content of ATP and ATP/ADP is decreased and AMP was increased in the mtDM group compared with T2DM group. Moreover,in T2DM group,the decreased ATP and ATP/ADP and the increased ADP and AMP was found compared with Normal group. In the T2DM group,the content of ATP is positive corralated with the of activity of SOD and SOD/MDA, ATP/ADP is positive corralated with activity of GSH-Px.3.0xidative stress and diabetic complication.Rsults indicated decreased activity of SOD and CAT were risk factors significantly associated with the occurrence of the diabetic neuropathy, retinopathy and diabetic nephrapathy.Decreased level of SOD and increased activity of MDA was aggravated following the advanced diabetic retinopathy. However there is no risk factor in the marker of oxidative stress of macrovascularpathy complication.4.0xidative stress and some clinical and biochemistric feature of diabetes.The content of MDA are related with the level of uric acid.In the overweighted diabetic group,the increased of MDA are found,there are decreased tendency of activity of SOD and GSH-Px.In the Normal group, there are negative correlation between MDA and HOMA-IR.Following the aging,activity of SOD is decreased and level of MDA is increased.The difference of activity of SOD and level of MDA between the Normal and T2DM group is most prominence in the Elderly than other age.Conclusion: Oxidative stress in the peripheral blood is raised and content of ATP in erythrocyte is decreased in the hyperglycemia.Diabetes mellitus due to themutation of the mitochodrial DNA own the aggravated oxidative stress and consumption of ATP compared with Type 2 diabetes without mtDNA mutation.Oxidative stress is one of risk factor of the microvascular complication of diabetes mellitus including diabetic neuropathy > retinopathy rather than macrovascular disease. Moreover, Overweight.aging and increased uric acid in plasma can aggravate the oxidative stress in diabetes mellitus.