The Levels And Clinical Significance Of Plasma ADMA And TGF-β1 In Patients With Type 2 Diabetic Nephropathy

ObjectiveTo study the levels and clinical significance of plasma asymmetrical dimethylarginine(ADMA)and transforming growth factor-β1(TGF-β1) in patients with type 2 diabetic nephropathy(DN).MethodsSixty-two patients with type 2 diabetic mellitus,35 males and 27 females ,the average age (62.75±11.30) years, were recruited. Based on the conditions that diabetic fundus changes, more than five years'course of type 2 diabetic mellitus and proteuria, the patients were divided into two groups.(26 cases for Non-Diabetic Nephropathy group,Non-DN group and 36 cases for diabetic Nephropathy group, DN group, respectively).Twenty sex-and age-matched healthy Chinese volunteers were recruited as normal controls. Individuals with acute and/or macrovasculary complications of diabetic mellitus , primary and other secondary kidney disease, acute or chronic infection,tumour, uncontrolled hypertension and dialysis, etc were excluded.Concentrations of ADMA and TGF-β1 in plasma were measured by Enzyme linked immunosorbent essay (ELISA). And the clinical and laboratory data of the patients were collected.The methods of statistical analysis included Independent-Samples T test, One-Way ANOVA, linear correlation, linear regression, Spearman's rank correlation and multivariate linear regression analysis.SPSS16.0 was used for statistical analysis. P values less than 0.05 were considered significant.Results1.Compared with normal controls, the levels of plasma ADMA in patients with type 2 diabetic mellitus with or without nephropathy were significantly increased(P<0.05, P<0.01,respectively);and DN group were higher than Non-DN group(P<0.01).2.Compared with normal controls, the levels of plasma TGF-β1 in patients in Non-DN group and DN group were significantly increased(P<0.05, P<0.01,respectively); and DN group were higher than Non-DN group(P<0.01).3. (1).The levels of plasma ADMA were positively correlated with TGF-β1 in patients with DN(r=0.524,P<0.01),and existed linear regressive correlation between them.(2).In non-DN group, the levels of plasma ADMA had no correlation with TGF-β1.(3).In all of T2DM, the levels of plasma ADMA were positively correlated with TGF-β1; and existed linear regressive correlation between them.4.(1)In DN group, the levels of plasma ADMA were positively correlated with hsCRP, serum creatine(SCr), 24 hours proteuria, proteuria/creatine ratio(Upro/Ucr)(P<0.05, P<0.01);and reversely correlated with estimated glomerular filtration rate(eGFR).There were no correlation between plasma ADMA and ALB,HDL,LDL,TC,TG.Multiple stepwise regression analysis showed that Upro/Ucr and hsCRP were related factors which influenced on the level of plasma ADMA.(2).In non-DN group, the levels of plasma ADMA were positively correlated with HbA1c(r=0.446,P<0.05),and had no correlation with DBP,SBP,ALB, and so on.(3).In all T2DM, the levels of plasma ADMA were positively correlated with hsCRP,HbA1C,SCr,24 hours proteuria and Upro/Ucr(P<0.05, P<0.01);and reversely correlated with eGFR.5. (1) In DN group, the levels of plasma TGF-β1 were positively correlated with hsCRP,HbA1C,SCr,24 hours proteuria,Upro/Ucr(P<0.05, P<0.01);and reversely correlated with eGFR;and had no correlation with ALB,HDL,LDL,TC,TG. Multiple stepwise regression analysis showed that ADMA was a related factor which influenced on the level of plasma TGF-β1.(2)In non-DN group, the levels of plasma TGF-β1 were positively correlated with Upro/Ucr(r=0.503, P<0.05),and had no correlation with other clinical indexes. (3).In all T2DM, the levels of plasma TGF-β1 were positively correlated with hsCRP,HbA1C,SCr,24 hours proteuria and Upro/Ucr(P<0.05, P<0,01);and reversely correlated with eGFR; and had no correlation with other clinical indexes.Conclusions1. The levels of plasma ADMA and TGF-β1 are significantly elevated in patients with type 2diabetic nephropathy, and the levels of them are both positively correlated with Pro-U/Cr and SCr, reversely correlated with eGFR. The results suggest that ADMA and TGF-β1 may play an important role in the pathogenesis of diabetic nephropathy.2. The elevated plasma ADMA in patients with type 2 diabetic nephropathy may partly owe to proteuria and chronic inflammatory, not to renal excretion obstacle.3. ADMA may play an important role in the pathophysiological of type 2 diabetic nephropathy by inducing TGF-β1 expression.