Levels Of VEGF And VEGF-A In Type 2 Diabetic Nephropathy And The Changes After Liraglutide Treatment

Objective:1.To compare the levels of serum vascular endothelial growth factor(VEGF)and its subtype VEGF-A among different clinical courses of type2 diabetic nephropathy(DN)in patients with type 2 diabetes.Study the relationship between serum VEGF,VEGF-A and 24h urinary microalbumin in T2DM patients with DN.Investigate whether VEGF and its subtype VEGF-A are related to the occurrence and development of diabetic nephropathy.2.We had the patients with early type 2 DN treated with glucagon like peptide 1(GLP-1)analog,liraglutide,and then compared their serum levels of VEGF,VEGF-A and 24h urinary microalbumin before and after treatment.The aim of the study was to explore whether the effect of liraglutide on the kidney is related to the expression level of VEGF and VEGF-A in patients with DN.Methods:1.92 inpatients diagnosed with type 2 diabetes were enrolled in our study.According to their 24h urinary microalbumin,total 92 type 2diabetes subjects were divided into three groups:normoalbuminuria group(group A),microalbuminuria group(group B),macroalbuminuria group(group C).At the same time,40 healthy people from medical center were enrolled as the control group(group D).The levels of serum VEGF,VEGF-A and 24h urinary microalbumin in the whole subjects were detected.2.Patients who had microalbuminuria(early DN)and did not control their serum glucose well after 1 month treatment with metformin,were randomly divided into two groups.Combined with metformin treatment,one group was treated with liraglutide and the other was treated with insulin glargine for 12 weeks.The changes of serum VEGF,VEGF-A and24h urinary albumin,blood glucose,blood lipid,waist circumference,waist to hip ratio were compared before and after treatment.3.Statistical analysis:SPSS19.0 software was used to analyze and process the data.The statistical methods we used included descriptive statistical analysis,analysis of variance,t test,Spearman correlation analysis and other methods for statistical data.Results:1.Compared with the control group,VEGF increased in the study group(group A ~aP<0.05,group B and C ~bP<0.01).VEGF-A increased more significantly(~b P<0.01),and Group C>group B>group A>group D.2.Correlation analysis:the serum levels of VEGF and VEGF-A were positively correlated with urine microalbumin in patients with type 2diabetes(r_s values were 0.363,0.721,respectively.P<0.05).Using VEGF and VEGF-A as the test variables,urine microalbumin as the state variable for the ROC curve,showing VEGF-A area under curve larger than VEGF.3.The patients with early DN were treated with liraglutide or insulin glargine.After 12 weeks of treatment,fasting and postprandial blood glucose,HbAlc decreased(P<0.01)compared with before treatment.And the difference before and after treatment in both groups considerable(P>0.05).24h urinary microalbumin and the serum levels of VEGF and VEGF-A decreased significantly in patients treated with liraglutide(P<0.01),while there was no significant decrease in patients treated with insulin glargine(P>0.05).The difference of VEGF and VEGF-A between the two groups was statistically significant(P<0.05 and P<0.01 separately).The waist circumference,waist-to-hip ratio,total cholesterol and triglyceride in liraglutide group decreased(P<0.05).Conclusion:1.Serum VEGF and VEGF-A were associated with the occurrence and development of DN,and the sensitivity of VEGF-A was higher.2.The protective effect of liraglutide on diabetic nephropathy is independent of lowering blood glucose,suggesting that it may be related to the inhibition of overexpression of VEGF and VEGF-A levels,thereby delaying the progression of diabetic nephropathy.