The Effect Of Glucose Variability On Oxidative Stress In Patients With Type 2 Diabetes

Objective: To investigate the amplitude of glucose variability and oxidative stress in type 2 diabetic patients, analyze the relationship between glucose variability and oxidative stress . At the same time, we performed a clinical trial to compare the effect of repaglinide and gliclazide on glucose variability and oxidative stress.Methods: A randomized, controlled, prospective study was used, 40 patients with type 2 diabetes mellitus and 10 healthy controls (group A) were enrolled in our study. Type 2 diabetic patients were divided into two groups: group B (n=20): treatment with repaglinide (1.5～6mg/d); group C (n=20): treatment with gliclazide (30～60mg/d). They were all received treatment for four weeks. Glutathione Peroxidase (GSH-Px) was measured by dithio-bis-nitrobenzoic acid assay (DTNB assay). Superoxide Dismutase (SOD) was determined by xanthine oxidase assay (hydroxylamine assay) . Maleic Dialdehyde (MDA) was measured by thiobarbituric acid colorimetry (TBA assay). Other metabolic variables were measured, including blood pressure, body mass indexes, waist/hip ratio, plasma glucose (0' ,30' ,45' ,60' ,90' ,120' ,180' ,240' ) and glycosylated hemoglobin (HbA1c) .Results: Glucose variability was assessed by the slope rate and mean postprandial incremental area under the curve (AUCpp), which obtained from fitting curve of human glycometabolism . The serum GSH-Px, SOD and MDA activity were measured to assess oxidative stress. The slope rate and AUCpp in type 2 diabetic patients were significantly higher than those in healthy adults (p<0.01), patients had lower serum GSH-Px and SOD concentration, but a higher serum MDA activity than the controls (p<0.01). After treatmented with repaglinide and gliclazide , the slope rate and AUCpp significantly decreased (p<0.01), and there were significant increase in serum GSH-Px and SOD levels, decreased in serum MDA activity (p<0.01), but the two group show no statistical difference (P>0.05). Using Pearson and partial correlation analyze, serum GSH-Px and SOD levels were negatively correlated with slope rate and AUCpp, but serum MDA activity was positively correlated with slope rate and AUCpp.Conclusion: Amplitude of glycemic variability and oxidative stress levels are significantly increased in type 2 diabetic patients. The serume oxidative stress levels are significantly correlated with changes of glucose variability. Repaglinide and gliclazide therapy can significantly reduce the amplitude of glycemic variability and oxidative stress levels in type 2 diabetic patients, but both had similar effect.