Study On The Relationship Between Serum Betatrophin Level And Urinary Albumin Creatinine Ratio In Type 2 Diabetes Mellitus Patients

ObjectiveDiabetic nephropathy is one of the major complications of diabetes,and microalbuminuria is its earliest performance.Betatrophin is a newly discovered secretory protein which involved in the metabolism of glycolipids.Some studies have found that serum betatrophin levels are significantly elevated in patients with diabetic nephropathy(DN).However,knowledge regarding the relationship between betatrophin and DN in humans is limited.This study measured serum betatrophin between normal control,normal albuminuria and abnormal albuminuria,and explored the correlations between its serum levels and DN.MethodsA total of 150 subjects were enrolled in this study.The participants were divided into newly diagnosed T2 DM patients(n=90)and age-and sex-matched normal control subjects(n=60).The T2 DM group was divided into normal albuminuria group(60 cases)and abnormal albuminuria group(30 cases)based on(UACR)?30mg/g.Anthropometric characteristics were measured.Glycosylated hemoglobin(HbA1c),fasting plasma glucose(FPG),fasting insulin(FINS),2h postprandial plasma glucose(2hPG),lipids and serum creatinine and other biochemical parameters were also detected,then homeostasis model of insulin resistance(HOMA-IR),homeostasis model of ?-cell function(HOMA-?)and glomerular filtration rate(GFR)were calculated.The UACR of T2 DM patients were determined by immunoturbidimertry,and fasting serum betatrophin concentrations were measured by enzyme-linked immunosorbent assay(ELISA).Results(1)Compared with the normal control group,HbA1 c,FPG,2hPG,HOMA-IR,triglyceride(TG),total cholesterol(TC)and low-density lipoprotein(LDL-C)in normal albuminuria group were significantly increased(P<0.05 or P<0.01),while HOMA-? was significantly decreased(P<0.01).HbA1 c,FPG,2hPG,TG,HOMA-IR and blood urea nitrogen(BUN)in abnormal albuminuria group were significantly increased than in normal control subjects(P<0.05 or P<0.01),while HOMA-? was significantly decreased(P<0.01).Compared with the normal albuminuria group,BUN,24 h-urinary albumin excretion(24hPRO)and UACR in abnormal albuminuria group were significantly increased(P<0.05 or P<0.01).(2)Serum betatrophin levels in normal albuminuria and abnormal albuminuria patients were significantly higher than in normal control subjects(P<0.01).Serum betatrophin levels in abnormal albuminuria patients were also significantly higher than in normal albuminuria(P<0.05).(3)According to the levels of serum betatrophin,T2 DM patients were divided into three groups,Tertile1,Tertile2 and Tertile3.Compared with the Tertile1 group,waist circumference(WC),waist-to-hip ratio(WHR),2hPG and HOMA-IR in Tertile2 and Tertile3 group were significantly increased(P<0.05 or P<0.01).The HbA1 c and creatinine(CREA)in Tertile3 group were significantly increased(P<0.05 or P<0.01),while GFR was significantly decreased(P<0.05)than in Tertile1 group.Compared with the Tertile2 group,age and CREA in Tertile3 group were significantly increased(P<0.05 or P<0.01),while GFR was significantly decreased(P<0.01).(4)Serum betatrophin levels in T2 DM patients positively correlated with age,WHR,HbA1 c,FPG,2hPG,FINS,HOMA-IR,BUN,CREA and UACR(P<0.05 or P<0.01),but negatively with GFR(P<0.01).After adjustment for age and WHR,HbA1 c,FPG,2hPG,FINS,HOMA-IR,CREA and UACR still significantly positively correlated with serum betatrophin levels(P<0.05 or P<0.01),while GFR still significantly negatively correlated with serum betatrophin levels(P<0.01).(5)Multivariate regression models were fit for betatrophin as a dependent variable,the variables that single factor linear regression analysis showed significant statistical significance as independent variables to demonstrate the relative contribution to the outcome ones.The results showed that WHR(?=1505.740,P=0.014),HOMA-IR(?=49.292,P=0.007),HbA1c(?=47.564,P=0.019)and GFR(?=-883.586,P=0.000)were independently related factors influencing serum betatrophin level(R2=0.312,P=0.000).(6)Binary logistic regression analysis showed that circulating betatrophin was significantly associated with UACR even adjustment for age,body mass index(BMI),HbA1 c,TG,LDL-C,HDL-C and blood pressure.Betatrophin was a risk factor of UACR.Conclusions(1)Our results indicated that serum betatrophin levels were significantly increased in T2 DM patients with elevated UACR.(2)Serum betatrophin levels were associated with UACR positively and GFR negatively.The trend in the presence of DN was more apparent in higher serum betatrophin tertile group.(3)High levels of serum betatrophin were the risk factor of proteinuria,which may play an important role in the pathogenesis of DN.