| ObjectiveTo observe the effects of inflammatory cytokines serum wingless-type MMTV integration site family member 5a(Wnt5a),secreted frizzled-related protein 5(sFRP5)levels on carotid intima media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM)and analyze the correlative factors.To investigate the possible mechanism of serum Wnt5 a and sFRP5 in the occurrence and progression of T2 DM macrovascular disease.Methods163 T2 DM patients hospitalized in the Department of Endocrinology of Henan Provincial People’s Hospital from September 2020 to December 2021 were selected as T2 DM group,aged 25 ～ 75 years,with diabetes course of 2 ～ 15 years.In addition,50 age-matched healthy subjects from the Health Management Department of our hospital were selected as the control group.Carotid ultrasound was used to measure the intima thickness at 1.0 ～ 1.5mm from the common carotid artery bifurcation at both sides of all subjects,taken the mean value as CIMT.T2 DM patients were divided into three groups according to CIMT:60 cases without carotid intima thickening were without thickened group,48 cases with carotid intima thickening were thickened group and 55 cases with carotid atherosclerotic plaque were plaque group.Recorded gender,age,diabetes course,smoking history,drinking history,height,weight,blood pressure of all subjects,calculated body mass index(BMI).5ml venous blood of all subjects were received the next day.Those samples were sent to the clinical laboratory of our hospital to determine hemoglobin A1c(Hb A1c),fasting blood glucose(FPG),fasting insulin(FIns),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C).Homeostasis model assessment for insulin resistance(HOMA-IR).Another 5ml venous blood was extracted to detect the levels of serum Wnt5 a,sFRP5,interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1)by enzyme linked immunosorbent assay(ELISA).Carotid ultrasound was used to measure the intima thickness at 1.0 ～ 1.5mm from the common carotid artery bifurcation at both sides of all subjects,taken the mean value as CIMT.The clinical data and inflammatory factors were compared between control group and T2 DM group,then the clinical data and inflammatory factors were compared in without thickened group,thickened group and plaque group,and analyzed the correlation of serum Wnt5 a,sFRP5,CIMT with clinical data and inflammatory factors.Results1.Comparison of clinical data and inflammatory factors between control group and T2 DM group:There were no significant differences in gender,age,smoking history,drinking history,BMI between control group and T2 DM group(all P > 0.05).The diabetes course,SBP,DBP,Hb A1 c,FPG,FIns,HOMA-IR,TC,TG,LDL-C,CIMT,IL-6,TNF-α,TGF-β1 in T2 DM group were higher than those in control group(all P < 0.05),HDL-C were lower than those in control group(P < 0.05).Wnt5 a in T2 DM group [1.21(0.82,1.49)ng/ml] were higher than those in control group [0.59(0.49,0.73)ng/ml](P < 0.05),sFRP5 [42.34(38.21,48.24)ng/ml] were lower than those in control group [56.97(46.73,64.45)ng/ml](P<0.05).2.Comparison of clinical data and inflammatory factors in without thickened group,thickened group and plaque group: There were no significant differences in gender,drinking history,BMI,FPG in without thickened group,thickened group and plaque group(all P > 0.05).Age,diabetes course,smoking history,SBP,DBP,Hb A1 c,FIns,HOMA-IR,TC,TG,LDL-C,CIMT,IL-6,TNF-α,TGF-β1 in plaque group were higher than those in thickened group and without thickened group,thickened group were higher than those in without thickened group(all P < 0.05).HDL-C in plaque group were lower than those in thickened group and without thickened group,and there was no statistical difference between thickened group and without thickened group.Wnt5 a in plaque group [1.55(1.35,1.74)ng/ml] were higher than those in thickened group [1.21(1.07,1.35)ng/ml] and without thickened group [0.75(0.68,1.06)ng/ml](P< 0.05),thickened group were higher than those in without thickened group(P < 0.05).sFRP5 in plaque group [39.00(34.63,42.30)ng/ml] were lower than those in thickened group [42.81(38.29,46.31)ng/ml]and without thickened group [49.07(39.40,64.00)ng/ml],thickened group were lower than those in without thickened group(P < 0.05).3.Correlation analysis of serum Wnt5 a,sFRP5 with clinical data and inflammatory factors:(1)Serum Wnt5 a was positively correlated with age,diabetes course,Hb A1 c,HOMA-IR,TG,CIMT,IL-6,TNF-α,TGF-β1(r = 0.425,0.476,0.467,0.330,0.227,0.717,0.465,0.453,0.631,all P < 0.05).Serum Wnt5 a was negatively correlated with HDL-C,sFRP5(r =-0.303,-0.400,P < 0.05).(2)Serum sFRP5 was positively correlated with HDL-C(r = 0.233,P < 0.05).Serum sFRP5 was negatively correlated with age diabetes course,Hb A1 c,HOMA-IR,TG,CIMT,Wnt5 a,IL-6,TNF-α,TGF-β1(r =-0.157,-0.255,-0.311,-0.236,-0.263,-0.486,-0.400,-0.331,-0.307,-0.451,all P < 0.05).4.Correlation analysis CIMT with clinical data and inflammatory factors: CIMT was positively correlated with age,diabetes course,SBP,DBP,Hb A1 c,HOMA-IR,TC,TG,LDL-C,IL-6,TNF-α,TGF-β1(r = 0.426,0.522,0.386,0.252,0.536,0.419,0.350,0.313,0.336,0.544,0.524,0.803,all P <0.05).CIMT was negatively correlated with HDL-C(r =-0.379,P < 0.05).5.Multiple linear regression analysis of influencing factors of serum Wnt5 a,sFRP5:(1)With Wnt5 a as dependent variable Y,and diabetes course,Hb A1 c,HOMA-IR,TG,HDL-C,IL-6,TNF-α,TGF-β1 as independent variable X.The results showed that: diabetes course,Hb A1 c,HDL-C,IL-6,TGF-β1 were independent influencing factors of Wnt5a(β’ = 0.162,0.181,-0.119,0.158,0.358,all P <0.05).(2)With sFRP5 as dependent variable Y,and diabetes course,Hb A1 c,HOMA-IR,TG,HDL-C,IL-6,TNF-α,TGF-β1 as independent variable X.The results showed that: Hb A1 c,TG,TGF-β1 were independent influencing factors of sFRP5(β’ =-0.182,-0.157,-0.305,all P < 0.05).6.Logistic regression analysis the influencing factors of carotid vascular disease in T2 DM patients: The thickened group and plaque combination of T2 DM patients were divided into the carotid vascular disease group.The presence or absence of carotid vascular disease was changed into a dependent variable(0 = no,1 = yes),and age,diabetes course,SBP,DBP,Hb A1 c,HOMA-IR,TG,HDL-C,LDL-C,Wnt5 a,sFRP5 were used as independent variables.The results showed that: age,diabetes course,Hb A1 c,TG,sFRP5 were independent influencing factors of carotid vascular disease in T2 DM patients,sFRP5 was protective factor and age,diabetes course,Hb A1 c,TG were risk factors.7.ROC curve of serum Wnt5 a and sFRP5 in predicting carotid vascular disease in T2 DM patients:(1)ROC curve of serum Wnt5 a in predicting carotid vascular disease in T2 DM patients: Area under curve(AUC)was 0.924,standard error(SE)was 0.02,sensitivity was 85.5%,specificity was 85.2%,Yuden index was 0.707,optimal truncation value was 1.315ng/m L,95%CI was 0.885 ～ 0.963.(2)ROC curves of serum sFRP5 in predicting carotid vascular disease in T2 DM patients: AUC was 0.772,SE was0.042,sensitivity was 63.3%,specificity was 87.4%,Yuden index was 0.507,optimal truncation value was45.83ng/m L,95%CI was 0.690 ～ 0.854.(3)ROC curve of serum Wnt5 a and sFRP5 combined in predicting carotid vascular disease in T2 DM patients: AUC was 0.925,SE was 0.021,sensitivity was 81.6%,specificity was 90%,Yuden index was 0.716,95%CI was 0.884 ～ 0.966.Conclusions1.Serum Wnt5 a levels were increased and sFRP5 levels were decreased in T2 DM patients with carotid vascular disease,both were closely related to CIMT.2.Serum Wnt5 a,sFRP5 may be involved in the occurrence and development of diabetic macrovascular complications through glucose and lipid metabolism,IR and inflammatory response.3.Combined detection of serum Wnt5 a and sFRP5 can improve the clinical predictive value of carotid vascular disease in T2 DM patients. |
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