| Objective: Detect the serum levels of D-lacticacid(DLA),diamine oxidase(DAO),lipopolysaccharide(LPS),and toll-like receptor 4(TLR4)of peripheral blood mononuclear cells(PBMCs)as well as its downstream signaling molecules-interleukin 6(IL-6)and high-sensitivity C-reactive protein(hs-CRP)-in patients with type 2 diabetes mellitus(T2DM)with or withoutmicroalbuminuria as well as in healthy subjects.This cross-sectional study was designed to investigate the mechanism of LPS-TLR4 singnaling in the occurrence and development of microalbuminuria in patients with T2DM.Methods: a total of 61 patients with T2DM were recruited from the department of Endocrinology in Gansu Provincial Hospital from December 2016 to june 2017,and all of the patients were stratified based on the levels of urinary albumin excretion rate(UAER): group of simple T2DM(UAER<20μg/min,32 subjects)and group of T2DM with microalbuminuria(UAER=20-200μg/min,29 subjects);and28 gender and age matched healthy subjects wereserved as group of healthy control.Flow cytometry was used to detect the expression of TLR4 in PBMCs.Serum levels of LPS,DLA,DAO,hs-CRP,IL-6,fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),low density lipoprotein(LDL),hi ghdensity lipoprotein(HDL),fasting insulin(Fins),glycosylated hemoglobin A1c(HbA1c)and liver and renal function were measured.All data were statistically analyzed using Statistical Product and Service Solutions(SPSS)version 19.0 developed by International Business Machines(IBM).Results:1 Comparison between groups:the levels of LPS,DLA,DAO,hs-CRP,IL-6 and TLR4 were increased in group of simple T2DM and group of T2DM with microalbuminuriaas compared with group of healthy control(P< 0.05 for all),and the levels of group of T2DM with microalbuminuria were higher than group of simple T2DM(P< 0.05 for all).2 Bivariate correlation analysis showed that thelevels ofLPS were positively correlated with FBG,HbA1 c,homeostasis model assessment of insulin resistance(HOMA-IR),hs-CRP,IL-6,UAER,DLA,DAO,TLR4,age,and disease duration(r=0.420,0.372,0.380,0.281,0.248,0.556,0.594,0.663,0.251,0.242,0.480,P<0.05 for all),and were negatively correlated HDL(r=-0.214,P<0.05);the levels of TLR4 were positively correlated with LPS,FBG,HbA1 c,HOMA-IR,hs-CRP,UAER,DLA,and disease duration(r=0.251,0.229,0.224,0.231,0.272,0.291,0.220,0.334,P<0.05 for all).3 Multivariate linear stepwise regression analysis demonstrated that the levels of TLR4(β=2.401,t=2.074,P=0.041),LPS(β=0.041,t=2.651,P=0.010),HbA1c(β=5.419,t=2.008,P=0.048),hs-CRP(β=6.211,t=2.546,P=0.013)and DLA(β=-11.787,t=-3.010,P=0.004)were independently related to the levels of UAER.Logistic regression analysis showed that the levels of FBG(OR=1.416,95%CI:1.046-1.917,P=0.024),LPS(OR=1.011,95%CI:1.005-1.017,P= 0.000),TLR4(OR=1.253,95%CI:1.009-1.556,P=0.003)and hs-CRP(OR=1.986,95%CI:1.265-3.120,P=0.003)were independently related to the occurrence of microalbuminuria in T2DM.Conclusions:1 Levels of LPS and TLR4 were independently associated with the occurrence and development of microalbuminuria in T2DM in both quantitative analysis and qualitative analysis;and high expression of LPS and TLR4 may be an independent risk factor for the occurrence of microalbuminuria in T2DM.2 LPS-TLR4 signaling pathway,which is often associated with impaired intestinal mucosal barrier function,may play an important role in the occurrence and development of microalbuminuria in T2DM. |
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