糖尿病肾病相关危险因素分析

　　作者：徐锦春1，陈思娇1，张　浩2，齐国先1，李廷富1，陈　婕1，高　阳1，宋今丹3 作者单位：1. 中国医科大学附属第一医院干部医疗工作部老年病教研室，辽宁 沈阳　110001;2.中国医科大学附属第一医院体检中心;3. 中国医科大学医学分子生物学研究所，卫生部细胞生物学重点实验室

　　【摘要】 目的：探讨影响糖尿病肾病的相关危险因素。方法：入选明确诊断2型糖尿病患者238例，根据尿微量白蛋白/尿肌酐的比值(UACR)分为糖尿病无肾病组(糖尿病1组，90例)，早期糖尿病肾病组(糖尿病2组，73例)，临床糖尿病肾病组(糖尿病3组，75例)，收集所有患者的临床资料，并检测餐前及餐后2h血糖(FBG、2hPB)，血脂、尿酸(UA)、纤维蛋白原(Fg)、糖化血红蛋白(HbA1c)等生化指标，并分析其与糖尿病肾病的相关性。结果：糖尿病1组、糖尿病2组、糖尿病3组的糖尿病病程[(7.25±6.29)年比(10.25±7.67)年比(13.53±7.82)年]、FBG[(8.46±2.52) mmol/L比(9.52±3.38) mmol/L比(10.82±3.30) mmol/L]、2hPB[(18.40±5.64) mmol/L比(20.27±5.94) mmol/L比(22.59±6.14) mmol/L]、HbA1c[(7.96±1.65)%比(8.60±1.76)%比(9.55±2.09)%]、甘油三酯[(1.72±0.86) mmol/L比(2.34±1.87) mmol/L比(3.16±1.85) mmol/L]、Fg[(3.49±0.93) g/L比(3.88±1.21) g/L比(4.99±2.10) g/L]、UA[(295.42±52.34) μmol/L比(324.18±96.29) μmol/L比(351.23±56.88) μmol/L]水平逐渐显著升高(P<0.05～<0.01)。Logistic逐步回归分析显示，糖尿病病程、HbA1c、TG、Fg、UA是糖尿病肾病的危险因素(优势比=1.008～1.910，P<0. 01～<0.001)。结论：糖尿病病程、血糖、血脂、血尿酸和纤维蛋白原是糖尿病肾病的危险因素;尿微量白蛋白/尿肌酐比值升高反映糖尿病人病情的进展，测定它有助于糖尿病的防治。

　　【关键词】 糖尿病肾病;白蛋白尿;危险因素

　　Abstract：Objective：To study relative risk factors for diabetic nephropathy (DN). Methods： A total of 238 patients diagnosed as type 2 diabetes mellitus (DM) were enrolled in the study. According to urine microalbuminuria to urine creatinine ratio (UACR)，patients were divided into pure DM group (group DM1，n=90)，early diabetic nephropathy group (group DM2，n=73) and clinical diabetic nephropathy group (group DM3，n=75). Clinic data of all patients were collected; Fasting blood glucose (FBG),2h postprandial blood glucose (2hPB)，blood lipids，uric acid (UA)，fibrinogen (Fg) and glycosylated haemoglobin (HbA1c) were measured in all patients，and their correlations with DN were analyzed. Results： Compared with group DM1，the course of disease in DM [(7.25±6.29) years vs. (10.25±7.67) years vs. (13.53±7.82) years]，levels of FBG [(8.46±2.52) mmol/L vs. (9.52±3.38) mmol/L vs. (10.82±3.30) mmol/L]，2hPB [(18.40±5.64) mmol/L vs. (20.27±5.94) mmol/L vs. (22.59±6.14) mmol/L]，HbA1c [(7.96±1.65)% vs. (8.60±1.76)% vs. (9.55±2.09)%]，triglyceride [TG，(1.72±0.86) mmol/L vs. (2.34±1.87) mmol/L vs. (3.16±1.85) mmol/L]，Fg [(3.49±0.93) g/L vs. (3.88±1.21) g/L vs. (4.99±2.10) g/L]and UA [(295.42±52.34) μmol/L vs. (324.18±96.29) μmol/L vs. (351.23±56.88) μmol/L]significantly increased in group DM2 and group DM3 in order (P<0.01～<0.001). Logistic gradual regression analysis indicated that course of DM，HbA1c，TG，Fg and UA were risk factors for DN (OR=1.008～1.910，P<0.01～<0.001). Conclusion：The course of DM，blood glucose，blood lipid，uric acid and fibrinogen are risk factors for diabetic nephropathy;increased UACR reflects progress of patients′ condition in DM patients，its detection is used for diabetic prognosis and treatment.

　　Key words： Diabetic nephropathies; Albuminuria; Risk factors

　　Diabetic nephropathy (DN) is one of major microvascular complications of type 2 diabetes mellitus (T2DM) and is a main cause of renal failure，and it′s an important cause of death and disability in DM patients. Unine microalbuminuria to urine creatinine ratio (UACR) is a stable，easy to examine，accurate and reliable index in early diagnosis of DN. Mechanism of DN development involves many factors. The present study analysed factors that influence development of DN，screened relative risk factors in order to perform effective intervention in early stage of nephropathy and delay development of DN.

　　1　Data and methods

　　1.1　Subjects

　　A total of 238 cases without kinship with each other diagnosed as T2DM admitted in department of endocrinology of our hospital from Jun 2008 to Jun 2009 were enrolled，including 121 males and 117 females with age 38～79，(64.12±15.85). T2DM was diagnosed according to diagnostic and exclusion standards established by WHO in 1999[1]. Patients with following diseases were excluded： acute complications of DM，hypertension，severe obesity，essential nephropathy，proteinuria or other renal damages caused by acute/chronic nephritis or pyelonephritis，severe cardiopulmonary or liver diseases，fever，post-exercise，stress，taking renal toxicity drugs or drugs that influence excretion of urine protein in recent period，taking drugs that influence blood lipids，clotting and excretion of uric acid. According to diagnostic standard of proteinuria in Chinese prevention and treatment guidelines for type 2 diabetic mellitus (2007 version)[2]，after creatinine corrected，urinary albumin excretion rate is presented as UACR (UACR： male： 22～220 mg/g，female： 31～220 mg/g were defined as microalbuminuria. UACR>220 mg/g was defined as massive proteinuria). Patients were divided into pure DM group (group DM1，n=90)，early diabetic nephropathy group (group DM2，n=73) and clinical diabetic nephropathy group (group DM3，n=75)according UACR level.

　　1.2　Indicators and methods

　　1.2.1　General data： Gender，age and course of disease in DM were collected and recorded.

　　1.2.2　Clinical indicators： Height，weight were measured and body mass index (BMI) was calculated in all subjects. After fasting for 10～12 h overnight，ulnar vein blood was taken in morning. Potassium oxalate and sodium oxide(2 mg/ml blood) were used for anticoagulation. Glucose oxidase method was used to measure fasting blood glucose (FBG) and 2h postprandial blood glucose (2hPB); automatic biochemical analyzer was used to measure blood lipids [total cholesterol (TC)，triglyceride (TG)，high density lipoprotein-cholesterol (HDL-C)，low density lipoprotein-cholesterol (LDL-C)]，renal function [blood urea nitrogen (BUN) and serum creatinine (Scr)]，uric acid (UA) and plasma fibrinogen (Fg); low-pressure liquid chromatography method was used to measure glycosylated haemoglobin (HbA1c，EDTA was used for anticoagulation of whole blood，EDTA vs. blood amount=1.5 mg/ml). Morning urine was collected for measuring urine micro albumin and urine creatinine by immunoturbidimetry method and UACR value was calculated then.

　　1.2.3　Definitions： (1) body mass index (BMI)： BMI= weight (kg) /height (m)2; (2) UACR：UACR= Unine microalbuminuria /urine creatinine，and the unit was mg/g.

　　1.3　Statistical process

　　SPSS 17.0 software was used for statistical analysis. Measurement data with normal distribution were presented as mean ± standard deviation(x-±s)，data without normal distribution were transformed into normal distribution after natural logarithmic transformation or were presented as median (quartile). Independent sample t test was used for comparison between two groups，Satterthwaite approximated t test was used for test of heterogeneity of variance. Forward conditional gradual Logistic regression analysis was used to analyze relative risk factors for DN. P<0.05 was regard as possessing significant difference.

　　2　Results

　　2.1　Comparison of general data and laboratory indexes among three groups with T2DM

　　There were significant difference in FBG,2hPB，HbA1c，TG，Fg and UA among three groups (P<0.05 all)，and levels of these indexes gradually increased from group DM1，to group DM2，group DM3 in order. There were no significant difference in age，gender，systolic blood pressure (SBP)，diastolic blood pressure (DBP)，BMI，TC，HDL-C，LDL-C，BUN and Scr among three groups (P>0.05). These were shown in Table 1.

　　2.2　Analyses of relative risk factors for DN

　　Complication of nephropathy in DM (1=yes,0=no) was regard as dependent variable and other clinical data were treated as independent variables to enter equation. Logistic gradual regression analysis show that strongest six relative risk factors for DN were course of DM，HbA1c，TG，Fg and UA (OR=1.008～1.910，P<0.05～0.01). There were no relationship among age，gender，BMI，SBP，DBP，FBG,2hPB，TC，HDL-C，LDL-C，BUN，Scr and occurrence of DN. These were shown in Table 2.　Table 1　Comparison of general data and laboratory indexes among three groupsTable 2　Logistic regression analysis for risk factors on incidence rate of DN

　　3　Discussion

　　DN is a common cause of renal failure and its prevalence rate is high in Asia-Pacific district[3]. In the USA，about 40% patients with end-stage renal disease (ESRD) were caused by DN and over 50% new ESRD patients every year were caused by DN[4]. In China,8% of total ESRD were caused by DN and it increased to 15% in some districts[5]. Early feature of DN is emerge microalbuminuria (MAN). The worse renal function is，the higher risk occurring cardiovascular diseases is. Thus，MAN should be regard as a risk factor for cardiovascular diseases and renal failure; intensive early prevention and treatment is a key for effective control of DN now. There are many factors influenced DN occurrence and development.Systemic endothelial function obstacle is a potential factor for MAN and vascular disease.MAN level upgrade suggests that widespread vascular damage occurred and permeability of general small arteries increased and arteriosclerosis aggravated.

　　Data of present study indicated that there existed significant difference in course of DM among three groups (P<0.05) and course of disease in DM was also an independent risk factor for DN，accorded with past studies[6]. The longer course of disease in DM is，the higher risk occurring DN is. When MAN occurs，course of disease is usually over five years and 80% patients with MAN develop into clinical DN in the next 10 years. Report from American Diabetes Association suggested that over 75% T2DM patients with obvious renal diseases will develop into ESRD in the next 20 years[7].

　　The present study indicated that levels of HbA1c，FBG and 2hPB in clinical DN group were significantly higher than those of pure DM group and early DN group (P<0.05～0.01)，suggesting that poor control of blood glucose is related with progression of DN and it′s consistent with overseas report[8]. Logistic regression analysis indicated that HbA1c，which may be better represent blood glucose control than FBG and 2hPB，was positively correlated with DN，suggesting that hyperglycemia may be an important risk factor for occurrence and development of DN.

　　The present study proved that Fg is also an independent risk factor for DN，therefore anticoagulation and antiplatelet treatments in early stage can delay occurrence and development of DN;also indicated that TG was positively correlated with occurrence of DN.Suggesting that hyperlipidemia may be an independent risk factor for DN. Because lipid metabolism disorder increases permeability of glomerular basement membrane and causes excretion of protein through changing phosphorylation ester composition on glomerular basement membrane.Meanwhile，it can cause atherosclerosis，increase excretion of urine protein[11]. Therefore，intensive blood lipid control can not only decrease diabetic macrovascular disease，but also decrease incidence rate and mortality rate of DN.

　　The present study indicated that increased UA level was a risk factor for DN，consistent with many past studies[9]. UA is mainly excreted in kidney，when glomerular filtration rate decreases，tubular reabsorption dysfunction occurs，blood UA level increases. Increased UA level can induce increase of renin expression in juxtaglomerular cells and inhibit expression of nitric-oxide synthase in macular densa. Meanwhile，increased UA can also damage vascular endothelial function and finally leads to glomerulosclerosis and albuminuria.

　　On the whole，interactions of prolonged course of disease in DM，poor control of blood glucose，hyperlipidemia，hypercoagulable state and hyperuricemia promote occurrence and development of DN.UACR is a sensitive index in diagnosis of early renal damage in DM. Therefore，early quantitative measurement of UACR is helpful for early diagnosis and treatment of DN and possess practical and clinical significance for prevention and delay occurrence of DN.

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　　[1]World Health Organization. Definition，diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1： Diagnosis and classification of diabetes mellitus. WHO/NCD/NCS/99.2.

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