| Background:Diabetic nephropathy is one of the most serious chronic complications of diabetes mellitus,as well as the primary cause of chronic kidney disease in China.With the improvement of living standards,the morbidity and mortality of diabetic nephropathy increased significantly year by year,which had affected the quality of people’s life and exerted tremendous pressure on the development of society.Nowadays,small portion could not achieved the therapeutic goals,even though multi-factor intervention for the therapy of diabetic nephropathy.Linagliptin had drawn much attention since it was listed.It is worth noting that many relative studies have found that linagliptin could protect the kidneys while controlling blood glucose,and this effect was beyond the improvement of blood glucose.However,little is known about the mechanism of linagliptin on protecting the kidney until now.Objective:In the present study,we examined the levels of the urinary albumin-to-creatinine ratio,serum HMGB1 and serum RAGE of the patients with diabetic nephropathy.Aim to observe the role of linagliptin in protecting the kidneys and infer the possible mechanisms,which will offers a new method for the treatment of diabetic nephropathy.Materials and methods:The study collected a total of 160 patients diagnosed with T2DM,as well as combined with diabetic nephropathy from Oct 2015 to Feb 2016,in the Second Hospital of Jilin University.In short,patients whose T2DM duration of 5~10 years combined with microalbuminuria,and whose eGFR was more than 60 ml/min/1.73m~2were eligible for the study.Those who infected with acute complications of diabetes mellitus,or combined with severe heart and liver dysfunction,or women in pregnancy or lactation were excluded.The participants were previously received insulin therapy with one or two hypoglycemic agents for more than 6 months(HbA1c levels of6.5~10.0%at screening),combined with hypertension and had received stable dose of antihypertensive drugs like ACEI/ARB for more than 4 weeks.The eligible patients’general informations and vital signs were collected,including gender,age,height,weight,BMI,SBP and DBP,followed by collecting the blood samples from cubital vein and the spot urine sample in the early morning.The participants were randomly divided into 2 groups,that is the linagliptin group(n=80)and the control group(n=80).The control group continued the background therapy,while the linagliptin group received linagliptin 5mg additionally.The FPG,2hPG,HbA1c,TC,TG,HDL-C,LDL-C,UACR,HMGB1and RAGE were measured per 12weeks.The primary efficacy outcome of our study was the change in UACR,the levels of serum HMGB1and RAGE from baseline to week 24.Results:1.A total of 160 subjects were pooled in the study.Among them,there were 39males with the age(57.62±9.51)years and 41 females with the age(59.40±10.61)years in the linagliptin group(n=80),42 males with the age(57.45±9.81)and 38females with the age(60.25±9.02)in the control group(n=80)(P=0.635).There was no statistical difference between the two groups at the baseline.2.After following up for 3-month,linagliptin group shows a significant reduction in FPG,2hPG,HbA1c,UACR,serum HMGB1 and RAGE compared with the baseline(P<0.001)and the control group(P<0.001),there was no statistical significance in the control group compared with the baseline about the above indexes(P>0.05).3.After following up for 6-month,the linagliptin group decreased significantly in FPG,2hPG,HbA1c,UACR,serum HMGB1 and RAGE compared with the baseline(P<0.001),3-month ago(P<0.001),and the control group(P<0.001),the control group shows a significant reduction in UACR from the baseline(P<0.001)and 3-month ago(P<0.001).4.The linagliptin group was divided into subgroups according to the average value of baseline SBP and baseline HbA1c.Further analysis between the subgroups shows that UACR decreased significantly than baseline when 6-month follow-up in each subgroup(P<0.001),but there was no statistically significant interaction between the subgroups(P>0.05).5.SBP and HbA1c were stratified into categories based on the change from baseline to 6-month follow-up in linagliptin group,further analysis shows that UACR decreased significantly than baseline when 6-month follow-up in each subgroup(P<0.001),but there was no statistically significant interaction between the subgroups(P>0.05).Conclusion:1.Linagliptin administered on top of stable RAAS inhibitors led to a significant reduction in patients with diabetic nephropathy,and its effect on the kidney independent on the control of either blood glucose or blood pressure.2.Linagliptin administered in addition to stable RAAS inhibitors reduced the level of serum HMGB1 and RAGE of the patients with diabetic nephropathy,and its effect of reducing urinary protein maybe relative to this. |
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