Exploration Of Early Diabetic Nephropathy Based On Risk Factor,Predictors And Syndrome Based On Objective Indexes

Objective1?To explore the main risk factors related in early diabetic nephropathy(DN)by epidemiological investigation.2?To explore the predictive value of biological indexes(EGF,APN,PTX3,RBP,uET)by the way of epidemiological investigation in early DN.3?To explore the relationship between indexes and syndrome types of Chinese medicine(CM)in early DN.4?To explore the relationship between indexes and early DN of blood-stasis syndrome.Methods182 hospitalized patients(group A)diagnosed as early DN definitely being from five hospitals(Wuhan Municipal Hospital of Chinese Medicine,Zhengzhou City Hospital of Chinese Medicine,Inner Mongolia Hospital of Chinese Medicine,the Affiliated Hospital of Inner Mongolia Medical University,and the First Affiliated Hospital of Beijing University of Chinese Medicine)from May 2010 to October 2011 were admitted,including 102 male patients and 80 female patients between the ages of 35 to 70 years old,with an average of 54.1±9.3 years old.While 170 hospitalized patients(group B)with pure DM was enrolled as the control,including 97 male patients and 73 female patients between the ages of 35 to 70 years old,with an average of 51.3±11.2 years old.Group A was further divided into two subgroups:syndrome of blood stasis(group A1,n=104),and syndrome of non-blood stasis(group A2,n=78).The normal(group of C,n=30)was also took as the control.The indexes in serum,plasma or urine were detected,which were glycosylated hemoglobin A1c(HbAlc),total cholesterol(TC),low density lipoprotein(LDL),high density lipoprotein(HDL),urinary albumin excretion rate(UAER),urinary epidermal growth factor(EGF),serum adiponectin(APN),serum endothelin(sET),tissue type plasminogen activator(t-PA),human plasminogen activator inhibitor 1(PAI-1),fibrinogen(Fib),plasma viscosity(PV),lower shear rate(LSR),serum cystatin C(CysC),nitric oxide(NO),serum C reactive protein(CRP),serum homocysteine(Hcy),serum pentraxin 3(PTX3),urinary retinol binding protein(RBP)and urinary endothelin(uET),higher shear rate(HSR)and erythrocyte metamorphosis index(TK).All patients' clinical materials were collected,including age,duration of diabetes,waist-to-hip ratio(WHR),systolic and diastolic pressure and so on.All patients'syndromes of CM were determined by three deputy director and above physicians.The data related were analyzed by the statistical method.There was not statistical significance in distribution of composition ratio,sex,age between group A and group B,also between group A1 and group A2,so they were comparable.Results1?Population materials comparison between groups:There was not statistical significance in sex ratio,nationality,education back-ground between group A and group B(P>0.05).Patients aged of 50 to 70 years old were the maximum proportion,accounting for 45.60%in early DN,the higher age,the higher attack.Patients aged of 50 to 59 years old were the maximum proportion,accounting for 50.00%in pure DM.Whereas,Patients aged of 60 to 70 years old decreased in pure DM.Distribution on duration of diabetes:10 year above accounted for 55.49%being the maximum proportion,followed by 5?10year accounted for 30.22%in group A.Whereas,5?10 year and 5 year below accounted for40.59%and 45.29%respectively in group B.Duration of diabetes comparison on 5 year below and 10 year above showed statistical significance between group A and group B(P<0.05).Smokers were more than non-smokers in early DN,difference between them was significant(P<0.05).Whereas,smokers were as more as non-smokers in pure DM,difference was not significant between group A and group B(P>0.05).Patients with habit of drinking were as more as who without in not only early DN but also pure DM,difference between them was not significant(P>0.05).2?Syndromes distribution:This study showed that in main syndromes of CM in early stage diabetic nephropathy,Qi-Yin deficiency syndrome(QY)accounted for 62.1%being the maximum proportion.Yin deficiency and excessive heat syndrome(YH)also was the chief syndrome type accounting for 21.9%.Whereas,both Yin-Yang deficiency syndrome(YY)and qi deficiency of spleen-kidney syndrome(SK)were less than ten percent accounting for 7.7%,8.2%respectively despite the two were the basic syndrome pattern in early DN.In accompanying syndromes of CM in DN of early stage,blood-stasis syndrome(BS)proportion was as high as 73.6%.Meanwhile heat-dampness syndrome(HD)was also the major syndrome type accounting for 30.8%,followed by phlegm-blood stasis(PD)syndrome accounting for 17.6%,cold-dampness syndrome(CD)accounting for 6.6%.The main syndromes in pure DM were Qi-Yin deficiency syndrome(QY)accounted for 57.1%being the maximum proportion.Yin deficiency and excessive heat syndrome(YH)also was the chief syndrome type accounting for 35.8%.Whereas,Yin-Yang deficiency syndrome(YY)accounted for7.0%in pure DM.Blood-stasis syndrome(BS)was the only accompanying syndrome in pure DM accounted for 48.2%.Cases difference showed statistical significance in both YH and BS between group A and group B(P<0.05).The main syndromes in early DN were Qi deficiency syndrome,Yin deficiency syndrome,blood-stasis syndrome,and damp-heat syndrome accounting for 70.33%,69.78%,73.6%,30.8%respectively,followed by Yang deficiency syndrome accounting for 7.69%.Whereas,phlegm-blood stasis syndrome(PB)and cold-dampness syndrome(CD)accounted smaller proportion which were 17.6%,6.6%respectively.The main syndromes in pure DM were Qi deficiency syndrome(n=97),Yin deficiency syndrome(n=109),Yang deficiency syndrome(n=12),blood-stasis syndrome(n=82)accounting for 57.06%,64.12%,7.06%,48.2%respectively.Cases difference in Qi deficiency syndrome showed obvious statistical significance between group A and group B except both Yin deficiency syndrome and Yang deficiency syndrome(P<0.05).3?Risk factors in early DN:Logistic analysis showed that the main risk factors of early DN were duration of diabetes,WHR,HbAlc and systolic pressure by logistic analysis(P<0.01).4?Comparison on TG,TC,HDL,LDL and HbAlc in different syndromes:The syndromes of CM in early DN were associated with indexes,such as TG,TC,HDL,LDL,HbAlc and so on,which changed from YH,SK,QY to YY.Whereas,the association between them was not specific.5?Comparison on UAER between syndromes:Comparison on UAER between syndromes showed statistical significance in early stage diabetic nephropathy between group A and group B except Yin-Yang deficiency syndrome(YY)(P<0.05).Comparison on UAER between syndromes showed statistical significance in early DN(P<0.05,P<0.01):between blood-stasis syndrome(BS)and non-blood stasis syndrome(NBS),between Yin deficiency syndrome(YD)and non-Yin deficiency syndrome(NYD),between Qi deficiency syndrome(QD)and non-Qi deficiency syndrome(NQD),between dampness-heat syndrome(DH)and non-dampness-heat syndrome(NDH),between phlegm-blood stasis syndrome(PB)and non-phlegm-blood stasis syndrome(NPB).While comparison on UAER between syndromes didn't show statistical significance in early stage DN(P>0.05):between Yang deficiency syndrome(YD)and non-Yang deficiency syndrome(NYD),between dampness-cold syndrome(DC)and non-dampness-cold syndrome(NDC).Comparison on UAER showed statistical significance in Qi deficiency syndrome between group A and group B(P<0.05).While no statistical significance was found in not only yang deficiency syndrome but also yin deficiency syndrome between them(P>0.05).6?Indexes Comparison between groups:?Compaired to group B,UAER,?1-MG,CysC,Hcy,uET,APN,PTX3,RBP,CRP increased,EGF decreaed in group A.The statistical diffrence was significant between them(P<0.05,P<0.01).?There was statistical significance in duration of diabetes,SBP,DBP,HbA1c,WHR,TG,HDL,Lp-?,UA and,GFR between group A and group B(P<0.05,P<0.01).While no difference was found between them in age,FPG,LDL,TC and CR(P>0.05).?Compaired to group A2,HbAlc,TC,TGQLDL,Fib,TK,PV,LSR,HSR,sET,PAI-1,Hcy,PTX3 in group A 1 increased,while NO and t-PA decreased,the difference between the two groups was significant except TC and HSR(P<0.05,P<0.01).?Compaired to group C,HbAlc,TG,TC,LDL,PV,TK,Fib,HSR,LSR,sET,PAI-1,Hcy,PTX3 in group A1 increased,while HDL,NO and t-PA decreased,the difference between the two groups was significant(P<0.05,P<0.01).7?Correlation analysis among indexes:During clinical work,we found diabetic patients with higher BMI were suffured from higher HbAlc,TG,TC,LDL,and patients with higher HbA1c were suffured from higher TG,TC,LDL,too,whose diabetic course was longer.So correlation among indexes was analyzed by spearman analysis.Positive correlation was found between HbAlc and TG,Course,also between WHR and TG,HbAlc(correlation coefficient was 0.542,0.725,0.471,0.582 respectively,P<0.05).Positive correlation was found between HbAlc and HSR,LSR,also between LSR and HSR(correlation coefficient was 0.62,0.70,0.80,P<0.05).TK was found positively correlated with HSR,PV,LSR(correlation coefficient was 0.33,0.82,0.44,P<0.05).Fib was also found positively correlated with TG,TC(correlation coefficient was 0.62,0.57,P<0.01).Positive correlation was also found between sET and PTX3,PAI-1(correlation coefficient was 0.52,0.62,P<0.05).Negtive correlation was found significantly between sET and NO,also between PAI-1 and t-PA(correlation coefficient was 0.78,0.66,P<0.01).While NO was positively correlated with t-PA(correlation coefficient was 0.41,P<0.05).Besides positive correlation was also found between APN and CRP,between UAER and APN,CysC,CRP(correlation coefficient was 0.731,0.614,0.563,0.562 respectively,P<0.05).Negtive correlation was found significantly between EGF and APN,UAER(correlation coefficient was 0.660,0.482,P<0.05).UAER waspositively correlatied with Hey,RBP,PTX3,?1-MG,uET(correlation coefficient was 0.715,0.586,0.649,0.479,0.673,P<0.05).Positive correlation was found significantly between uET and PTX3,also between RBP and ?1-MG(correlation coefficient was 0.562,0.468,P<0.05).Conclusion1?It was helpful to detect EGF,APN,PTX3,RBP,uET,CysC and Hey in predicting early DN.2?Qi-Yin deficiency syndrome and blood-stasis syndrome were the primary syndromes of CM in early DN.Activating blood and dissolving stasis as well as supplementing qi and nourishing yin were the primary treatment in early DN.3?Patients with early DN were suffering from hyperglycemia,hyperlipemia,inflamma-tion of non-infection,and from abnormality of hemorheology,vasoactive factor,fibrinolytic activity as well.Biological indexes related were relevant factor of blood-stasis syndrome,which was associated with antiinflammatory,endothelial protection,adjustment of fibrinolytic activity and hemorheology in treating early DN.4?Control of hyperglycemia,hypertension and weight loss as well as giving up smoking were helpful in delaying the development of diabetic nephropathy.