Prevalence Of Diabetic Nephropathy And Its Associations With ACE2 Gene Polymorphism And ACE/ACE2 Ratio In Type 2 Diabetes

Objective:(1)To analyze prevalence of diabetic nephropathy(DN)in hospitalized type 2 diabetic patients and its clinical characteristics.(2)To investigate the association between ACE2 gene polymorphism,serum ACE/ACE2 ratio and DN by a case-control study,in order to provide the scientific basis for exploring a new treatment approach on DN taking ACE/ACE2 as the therapeutic target.Methods:(1)2516 inpatients with type 2 diabetes mellitus(T2DM)were seleted as subjects from August 30,2011 to Aug 30,2012 in Metabolic Diseases Hospital of Tianjin Medical University,Tianjin,China.The Epi data database was established according to the medical records,which included name,gender,occupation,marital status,smoking,alcohol drinking,blood pressure,height,weight,waist circumference,hip circumference,the records of laboratory examination and so on.The clinical characteristics and stages of DN inpatients were analyzed.(2)A case-control study was conducted in Metabolic Diseases Hospital of Tianjin Medical University from April 26,2012 to October 1,2013 in order to investigate the association between ACE2 gene polymorphism,serum ACE/ACE2 ratio and DN.The subjects included 145 patients with DN as the case group and 141 T2DM patients without DN as the control group.Information was collected through face-to-face interview,physical examination and laboratory examination.Serum ACE and ACE2 activity were tested by enzyme-linked immunosorbent assay(ELISA).ACE2 gene G8790A polymorphism was tested by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The OR(95%CI)of ACE2 gene polymorphism,serum ACE/ACE2 ratio,and other factors for type 2 diabetic nephropathy were analyzed by logistic regression analysis.Results:(1)The prevalence of DN was 31.6%,of which 51.9%was in stage ?,15.2%in stage ?,32.9%in stage V of DN.Prevalence of DN in male type 2 diabetic patients(33.9%)was higher than in female patients(28.5%);Stage ?,?and V accounted for 47.6%,14.4%and 38.0%respectively in male DN patients,while 58.4%,16.6%and 25.0%respectively in female DN patients.The proportions of stages varyed in different aged patients with DN(?2=47.098,P<0.001).The proportion of Stage ? was lower and of Stage V was higher in older type 2 diabetic patients.The proportions of different DN stages also varyed in different diabetic duration(?2=39.776,P<0.001).The proportion of Stage ? was lower and of Stage ? was higher in2 type 2 diabetic patients with long duration.DN patients were diagnosed as diabetes in earlier age than non-DN patients and DN patients with stage? were diagnosed in later age than patients with stage ? and ? DN.The proportions of insulin use,eye diseases,peripheral neuropathy,hypertension,diabetic foot,hyperuricemia,hypocalcemia,hypokalemia and obesity(BMI 2 28 kg/m)were higher in DN patients than in patients without DN.Levels of serum albumin,globulin ratio,total bilirubin,direct bilirubin,fructosamine were lower,while serum urea nitrogen,creatinine,uric acid,TG,CRP,VLDL-C,fibrinogen,urine creatinine,urine protein,urinary albumin were higher in DN patients.(2)There was no significant difference in age,sex,ethnic group,occupation,education level and marriage between case group and control group.There wasn't significant difference in ACE2 genotype and allele frequencies between case group and control group.Logistic regression analysis showed that OR for DN was 0.230 in patients with serum ACE activity over 1.637U/L comparing with patients with ACE activity level<1.637U/L and ORs for DN were 0.148,0.459 and 0.098 respectively in patients with serum ACE2 activity levels 46.89U/L-,247.69 U/L-,422.09U/L-comparing with patients with ACE2 activity level<46.89U/L.After adjusting for age and sex,the relationship still existed.The OR for DN was 5.954 in patients with serum ACE/ACE2 ratio over 0.0392 comparing with patients with ACE/ACE2 ratio<0.0038.Logistic regression analysis also showed that physical exercise,lipid metabolism disorders,family history of hypertension,systolic blood pressure,serum TG,TC,LDL-C,urea nitrogen,creatinine,uric acid,FIB were statistically associated with DN occurrence.Multivariate logistic regression analysis showed that six factors come into the equation,i.e.physical exercise,systolic blood pressure,serum TG,creatinine,FIB,ACE/ACE2 ratio.Conclusions:1.The prevalence of DN was higher in older male and longer diabetic duration.The proportion of stage ? was lower and of stage V was higher in older DN patients with long duration.DN patients had poor glycemic control and higher proportion of insulin use.Prevalence of eye diseases,peripheral neuropathy,hypertension,diabetic foot,hyperuricemia,hypocalcemia,hypokalemia were higher in DN patients.Levels of serum albumin,globulin ratio,total bilirubin,direct bilirubin,fructosamine were lower in DN patients,while serum urea nitrogen,creatinine,uric acid,TG,CRP,VLDL-C,fibrinogen,urine creatinine,urine protein,urinary albumin were higher in DN patients.2.There wasn't significant difference in ACE2 genotype and allele frequencies between case group and control group.Logistic regression analysis showed that there was statistical association between serum ACE and ACE2 activity and DN.The ratio of ACE/ACE2 was higher in case group,the difference was statistically significant(Z=5.176,P<0.001).Multivariate logistic regression analysis showed that physical exercise,systolic blood pressure,serum TG,creatinine,FIB,ACE/ACE2 ratio were associated with the occurrence of DN.