2型糖尿病肾病患者25-羟维生素D水平变化及意义

目的探讨25-羟维生素D[25(OH)D]水平在2型糖尿病肾病患者中的检测价值。方法采用便利抽样与回顾性分析方法,选择2014年8月-2018年2月期间在湖北医药学院附属东风医院肾病内科诊治的糖尿病肾病患者180例作为研究对象,调查患者的临床资料,记录患者血清25(OH)D、尿白蛋白排泄率(UAER)水平,记录患者的病情状况并进行相关性分析。其中UAER≥300 mg/24 h表示存在糖尿病肾病;UAER≥30 mg/24 h表示存在微量白蛋白尿。结果在180例患者中,微量白蛋白尿50例,大量蛋白尿20例;平均血清25(OH)D水平为(31.0±15.5)ng/mL,大量尿蛋白组的血清25(OH)D水平也显著低于其他两组(P0.05)。维生素D正常组120例,不足组40例和缺乏组20例。维生素D缺乏组UAER显著高于其他两组(P0.05),3组血肌酐、高密度脂蛋白胆固醇(HDLC)、三酰甘油(TG)等比较也有显著性差异(P0.05),Pearson相关分析显示糖尿病肾病患者的血清25(OH)D水平与患者UAER、血肌酐呈显著负相关(P0.05),与HDL-C呈现显著正相关性(P0.05);通过开展多元线性逐步回归分析发现,血肌酐与UAER是影响血清25(OH)D水平的独立因素(P0.05)。结论血清25(OH)D在2型糖尿病肾病患者中呈现低水平,与患者的血脂与UAER有显著相关性,可影响患者的病情进展,其在临床上有很好的检测价值。     

2型糖尿病患者血清胆红素水平与糖尿病肾病的相关性

目的:探讨2型糖尿病患者血清胆红素水平与糖尿病肾病的相关性。方法:156例2型糖尿病患者,按照尿白蛋白排泄率水平分为正常蛋白尿组(n=54),微量蛋白尿组(n=50),大量蛋白尿组(n=52),比较患者一般资料及胆红素水平并进行分析。结果:三组间的总胆红素水平和直接胆红素水平,大量蛋白尿组微量蛋白尿组正常蛋白尿组,差异有统计学意义(P0.01)。Pearson相关分析表明,血清总胆红素与尿白蛋白排泄率呈负相关(r=-0.305,P0.01)。Logistic回归分析显示,总胆红素是糖尿病肾病的独立保护性因素(OR=0.832,95%CI:0.725~0.954,P0.01)。结论:总胆红素水平与尿白蛋白排泄率水平相关,胆红素的下降参与了糖尿病肾病的发生、发展。     

血清25（OH）D3与胰岛素抵抗及尿微量白蛋白的相关性研究

目的：观察2型糖尿病及糖调节受损患者血清25（OH）D3与胰岛素抵抗及尿微量白蛋白的相关性。方法：对820例健康体检人员进行筛查,共筛选出104例2型糖尿病患者（T2DM组）,其中初发糖尿病患者40例,既往诊断2型糖尿病患者64例,同时筛选出糖调节受损患者（IGR组）94例,选择同期170例非糖尿病血糖正常体检者为对照组（NGT组）。所有参与者记录身高、体重计算体重指数（ BMI）、并行口服糖耐量及胰岛素释放试验检测;留取血清,运用ELISA法检测血清25（OH）D3水平;放免法检测尿微量白蛋白（尿MA）;分析血清25（OH）D3与胰岛素抵抗及尿MA的相关性。结果：T2DM组及IGR组中25（OH）D3水平与对照组相比明显降低（P＜0.05）,2型糖尿病中有63.16%的患者维生素D缺乏,较非糖尿病患者（42.35%）明显增高（P＜0.05）;相关分析显示,血清25（OH）D3水平与空腹胰岛素呈正相关,而与年龄、BMI、空腹血糖水平、HOMA-IR、尿微量白蛋白呈负相关。结论：2型糖尿病患者血清维生素D缺乏非常严重,维生素D缺乏可能会加重胰岛素抵抗及促进尿微量白蛋白分泌。维生素D缺乏可能是2型糖尿病及糖尿病肾病发病中重要的危险因素。     

血清25( OH )VD水平在2型糖尿病患者中的状况

目的 糖尿病患者骨质疏松以及骨折的风险较非糖尿病患者增加,在1型糖尿病患者中表现明显,但对于2型糖尿病患者骨折的风险和骨密度的变化存在争议.本研究探讨25(OH)VD和骨转换指标在2型糖尿病患者的变化,分析其对骨代谢的影响.方法 收集2007.12至2011.10于我院就诊的437例未接受维生素D补充治疗的病程不超过5年的2型糖尿病患者(T2DM),同时收集非糖尿病的对照组(NDM)414例,测定各组患者骨生化指标,并收集临床资料以备数据分析使用.结果 与非糖尿病组患者相比,2型糖尿病患者血清25(OH)VD水平明显降低(P=0.001),骨特异性碱性磷酸酶(BAP)、抗酒石酸酸性磷酸酶(TRAP)水平升高,骨转换活跃;男性、女性2型糖尿病患者血清25(OH)VD水平均较非糖尿病组降低(P均＜0.001);相关分析显示,2型糖尿病患者血清25(OH)VD水平与空腹血糖呈负相关,而与糖化血红蛋白、HOMA-IR等无明显相关性.结论 2型糖尿病患者血清25(OH)VD水平明显低于非糖尿病者,且与空腹血糖呈负相关,糖化血红蛋白与25(OH)VD的相关性不如空腹血糖明显.     

糖尿病肾脏病患者尿白蛋白排泄率与骨代谢生化指标相关性分析

目的分析2型糖尿病患者尿白蛋白排泄率与骨代谢生化指标的相关性。方法选取2013年10月至2015年6月于重庆医科大学附属第一医院内分泌科住院的2型糖尿病患者302名。搜集其基本资料、骨代谢生化指标及骨密度等。按尿白蛋白排泄率(urinary albumin excretion rate,UAER)的水平将其分为正常白蛋白尿组(132名)、微量白蛋白尿组(101名)、大量白蛋白尿组(69名)。并作统计学分析。结果三组间骨密度(bone mineral density,BMD)比较差异无统计学意义,2型糖尿病患者25(OH)D3、1型前胶原氨基末端前肽(type I procollagen N-terminal propeptide,P1NP)在大量白蛋白尿组显著低于微量白蛋白尿组、正常白蛋白尿组(P0.05);随着UAER的升高,1型胶原羧基端肽β特殊序列(β-Carboxyl terminal peptide,β-CTX)逐渐升高、骨钙素(bone alkaline phosphatase,BGP)逐渐降低,大量白蛋白尿组、微量白蛋白尿组与正常白蛋白尿组比较差异有统计学意义(P0.05)。Spearman等级相关分析示P1NP、BGP、25(OH)D3与UAER呈负相关,β-CTX与UAER呈正相关。结论糖尿病肾脏病患者骨代谢生化指标的改变可能早于骨密度反映骨代谢异常。     

2型糖尿病患者HbA1C、25( OH )VD水平与骨密度的相关性研究

目的 观察2型糖尿病患者HbA1C、25 (OH)VD水平与骨密度(Bone Mineral Density,BMD)的相关性.方法 收集我院160例住院患者资料,以HbA1C水平分组,HbA1C<7%为组1(平均年龄52.47±11.39岁),HbA1C>8.5%为组2(平均年龄56.38±9.84岁),测定HbA1c、身高、体重、体重指数(Body Mass Index,BMI),采用美国Norland双能X线骨密度检测仪测定患者L2-4和左侧股骨近端(Neck、Troch、Ward's三角区)BMD,采用酶联免疫吸附法检测血清25(OH)VD,分析HbA1c、25(OH)VD、BMD三者的相关性.结果 两组患者身高、体重、BMI无显著性差异,2型糖尿病患者血清25(OH)VD水平与HbA1C呈负相关(r=-0.758,P<0.05),与腰椎骨密度无相关性(P>0.05),与髋部骨密度呈明显正相关(P＜0.05).结论 糖尿病患者血糖控制水平对25(OH)VD与骨密度有不良影响.     

2型糖尿病合并微血管病变与骨转换标志物的相关性

目的探讨2型糖尿病合并微量白蛋白尿、视网膜病变患者骨转换标志物的变化。方法选取301名成人2型糖尿病患者,将合并微量白蛋白尿和(或)视网膜病变患者作为试验组,无微量白蛋白尿和视网膜病变患者作为对照组,运用统计学分析比较两组间I型原胶原N-端前肽(procollagentype I N-terminal propeptide,PINP)、β-异构C-端肽(beta-isomerized Ctelopeptide,β-CTX)以及相关资料的差异,并对两组骨转换标志物进行相关性分析。结果两组间血清PINP的比较,差异无统计学意义(P0.05);试验组β-CTX明显高于对照组(P=0.001);相关分析显示β-CTX与BUN(γ=-0.431,P=0.013)、Cr(γ=-0.602,P=0.013)、UA(γ=-0.538,P=0.012)、25(OH)D3(γ=-0.703,P=0.036)呈负相关,与HbA1c(γ=0.235,P=0.030)、PTH(γ=0.652,P=0.000)呈正相关。结论 2型糖尿病合并微量白蛋白尿和视网膜病变时,β-CTX明显增高,认为β-CTX可能成为监测2型糖尿病微血管病变患者骨代谢变化的特异性指标。     

尿NGAL在2型糖尿病肾病肾小管间质损伤评价中的价值

目的探讨尿中性粒细胞明胶酶相关载脂蛋白(NGAL)对评价2型糖尿病肾病(DN)患者肾小管间质损伤的价值。 方法研究对象为2012年1月至2015年12月第三军医大学大坪医院2型糖尿病患者167例(2型糖尿病组);将2型糖尿病组再分为正常白蛋白尿组(n＝56)、微量白蛋白尿组(n＝58)、大量白蛋白尿组(n＝53),其中51例患者进行了肾活检。50例非糖尿病患者作为正常对照组。采用酶联免疫吸附测定方法检测尿液中NGAL水平,分光光度法测定尿N-乙酰-β-D-葡萄糖苷酶(NAG)。分析尿NGAL水平与肾功能相关指标[尿NAG、尿白蛋白/肌酐比值(ACR)、eGFR]及肾组织损伤病理评分之间的相关性,以及NGAL对DN肾小管间质损伤严重程度的评价效能,采用SPSS软件进行统计学分析,相关性分析采用Pearson或Spearman方法。 结果糖尿病患者尿NGAL水平较非糖尿病正常对照组明显增加;尿NGAL水平与尿NAG、ACR呈正相关(r＝0.528, 0.578,P<0.001),与eGFR呈负相关(r＝－0.637,P<0.001);尿NGAL水平与DN肾小管萎缩与间质纤维化(IFTA)的严重程度呈显著正相关(r＝0.652,P<0.001);尿NGAL曲线下面积最大(AUC＝0.868),特异度94.7%,敏感度71.9%。 结论尿NGAL是评价DN肾小管间质损伤理想的生物标志物之一。     

2型糖尿病患者微量白蛋白尿危险因素分析

目的：研究2型糖尿病微量白蛋白尿（MAU）的危险因素。方法：对47例2型糖尿病合并MAU的患者和56例2型糖尿病非合并MAU的患者的病程、年龄、血脂、血糖、血压、空腹胰岛素（FINS）和空腹C肽（F-CP）水平等因素进行分析比较，同时将微量白蛋白排泄率（UAER）与各指标进行相关分析和多元逐步回归分析。结果：2型糖尿病合并微量白蛋白尿组的、舒张压（DBP）、甘油三酯（TG）、载脂蛋白B(APOB)显著高于非合并微量白蛋白尿组，而高密度脂蛋白（HDL-C）则明显低于后者；UAER与年龄、病程、血压、空腹C肽（F-CP）、糖化血红蛋白（HbAlC）、TG、低密度脂蛋白（LDL-C）、APOB呈正相关，与HDL-C呈负相关；经多元逐步回归分析后得出：UAER与HbAlC、F-CP、TG、SBP、病程、APOB呈正相关，与HDL-C呈负相关。结论：2型糖尿病的病程长和以高TG、高APOB和低HDL为特征的脂代谢紊乱是糖尿病肾病的危险因素，高血压、HbAlC、高F-CP水平也是糖尿病的危险因子。     

尿8-OHdG检测在糖尿病肾病患者中的临床价值

目的：通过检测糖尿病肾病（DN）患者尿中DNA氧化损伤的主要的标记物8-羟基脱氧鸟苷（8-OHdG）,评价2型糖尿病患者早期肾脏病变与氧化应激的关系并探讨其临床意义。方法：选取DN患者90例,分为正常蛋白尿组,微量蛋白尿组、大量蛋白尿组各30例,检测尿8-OHdG,尿微量白蛋白、NAG等指标。结果：糖尿病组的尿8-OHdG水平显著高于正常对照组[（16.5±0.3） vs （10.8±0.5）ng/mg Cr,P〈0.01];微量蛋白尿组和大量蛋白尿组的尿8-OHdG水平明显高于正常蛋白尿组（P〈0.01）,大量蛋白尿组的尿8-OHdG水平显著高于微量蛋白尿组（P〈0.01）。 DN患者尿8-OHdG水平与总胆固醇、低密度脂蛋白呈正相关,与BMI及eGFR呈负相关。尿8-OHdG水平与尿微量白蛋白、尿NAG、α2-MG、FDP呈显著正相关。结论：DN 患者随着蛋白尿的增多及肾功能的进展其氧化应激水平增强,氧化应激的重要标志物8-OHdG作为重要因素参与DN的发生与发展。     

2型糖尿病患者微血管病变与骨密度相关性研究

目的探讨2型糖尿病患者微血管病变与骨密度的相关性。方法本横断面研究共纳入2 170例2型糖尿病患者(包括1 188名绝经后女性和982名50岁男性)。根据24 h尿蛋白水平对这些受试者进行分组:一组(30 mg)、二组(30～299mg)和三组(300 mg)。通过双能X射线吸收测定法评估其腰椎、髋部和股骨颈的骨密度。视网膜病的眼底照相和24 h尿蛋白作为2型糖尿病中微血管病的标志物。比较受试者的特征和骨密度。多变量分析用于研究骨密度与微血管病之间的关联。结果第三组在两种性别中具有最低的骨密度水平。在调整年龄、体重指数、高血压、高脂血症、糖尿病状态、肝功能、肾功能、性激素和25(OH)维生素D后,多变量分析显示,微血管病变与女性骨密度呈负相关(腰椎:r=-0. 522,P0. 001;髋关节:r=-0. 301,P=0. 010;股骨颈:r=-0. 314,P=0. 009),男性未发现相关性。结论绝经后女性2型糖尿病患者的微血管病变与骨密度之间呈负相关。     

Albuminuria: a target for treatment of type 2 diabetic nephropathy

Both renal and cardiovascular morbidity and mortality is increased markedly in patients with type 2 diabetes. Besides the classic risk factors and markers such as glucose, blood pressure, blood lipid profile, and lifestyle (smoking, overweight), novel risk markers are identified, among them urine albumin excretion. Levels of urinary albumin excretion greater than normal are observed frequently in patients with type 2 diabetes. Moderately increased levels of albuminuria, so-called microalbuminuria, are predictive both for progressive renal function loss to diabetic nephropathy, and for cardiovascular morbidity and mortality: the higher the albuminuria level, the more chance of renal and cardiovascular complications. More advanced levels of albuminuria (overt albuminuria) are observed in patients in the diabetic nephropathy state. In this condition, renal and cardiovascular risk are extremely high, and again one may observe that the level of albumin excretion is predictive of renal and cardiovascular outcome. Several drug strategies decrease the level of urinary albumin excretion in type 2 diabetic patients. Data on using drugs that intervene in the renin-angiotensin-aldosterone-system (RAAS) are the most extensive and conclusive. RAAS intervention is a very effective strategy to decrease the amount of albumin in the urine, independent from the blood pressure decreasing characteristics of the treatment. RAAS intervention is associated with long-term renal and cardiovascular protection. Importantly, the degree of short-term albuminuria decrease is associated with the degree of renal and cardiovascular protection: the more albuminuria reduction, the more protection. The protective predictive power of the albuminuria effect of RAAS intervention is not related to (or dissociated from) the blood pressure decreasing effect of these drugs. The protective effect of RAAS intervention is present at normoalbuminuric, microalbuminuric, and overt albuminuria levels. This makes albuminuria a target for therapy in type 2 diabetes. New drug strategies that decrease or prevent albuminuria without affecting other risk factors currently are being tested, and not only will add to underscoring the need to treat albuminuria as a separate target, but also will assist in reducing the enormous residual risk burden of individual diabetic patients.     

Change and clinical significance of microRNA-148b-3p level in the serum of patients with type 2 diabetes mellitus and diabetic nephropathy

Objective To detect the serum microRNA-148b-3p level in patients with diabetes mellitus and diabetic nephropathy, and to analyze its correlation with clinical and pathological indexes. Methods The research crowd was divided into three groups (1) diabetic nephropathy group: biopsy with diabetic nephropathy (n=25, 14 males, 11 females); (2) type 2 diabetes mellitus group: type 2 diabetes mellitus patients with normal urinary microalbumin /urinary creatinine value (n=10, 4 males, 6 females); (3) normal control group: healthy subjects (n=9, 3 males and 6 females). Clinical indicators included gender, age, 24-hour urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), urea (Urea), cystatin-C (Cys-C), blood albumin (ALB), urine microalbumin (UMA), triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum uric acid (UA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), urine microalbuminuria / urinary creatinine (UACR), and estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula. Real-time quantitative PCR was applied to verify the expression of microRNA-148b-3p in serum samples of the research crowds. The relationships between microRNA-148b-3p level and clinical features was also analyzed. Results The levels of serum microRNA-148b-3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group (P＜0.05, respectively). The level of serum microRNA-148b-3p was significantly correlated with HDL-C (r=-0.374, P=0.013), UMA (r=0.426, P=0.004), FBG (r=0.330, P=0.046) and TG (r=0.423, P=0.005). Multiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level (β=0.338, P=0.044). The area under the receiver operating characteristic curve (ROC) of serum microRNA-148b-3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665, respectively. Conclusions The level of serum microRNA-148b-3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases. The level of UMA is independently associated with serum microRNA-148b-3p level. Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic nephropathy.     

Usefulness of a highly sensitive urinary and serum IL-6 assay in patients with diabetic nephropathy

BACKGROUND/AIM: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. METHODS: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. RESULTS: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 +/- 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 +/- 0.6 pg/ml in patients with microalbuminuria and then to 4.4 +/- 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. CONCLUSION: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.     

糖尿病肾病患者血清vaspin与血清脂联素的相关性

目的 探讨血清vaspin、血清脂联素水平与糖尿病肾病的相关性.方法 选择120例2型糖尿病患者,据尿白蛋白排泄率分为正常蛋白尿组(尿白蛋白排泄率＜ 20μg/min)40例、微量蛋白尿组(尿白蛋白排泄率20～200 μg/min)45例、大量蛋白尿组(尿白蛋白排泄率＞200μg/min)35例,另选健康体检者40名为对照组.分别采用酶联免疫吸附法测定空腹vaspin、脂联素水平,同时测定空腹血糖、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹胰岛素、尿素氮、血肌酐,测量体质指数、腰围、收缩压和舒张压,比较各组间差异.结果 3组患者较对照组血清vaspin、脂联素水平显著升高,差异有统计学意义(P＜0.05).3组患者随着尿白蛋白排泄率升高,血清vaspin水平逐渐降低,差异无统计学意义(P＞0.05);随着尿白蛋白排泄率升高,血清脂联素水平逐渐升高,差异有统计学意义(P＜0.05).血清vaspin与体质指数、腰围、收缩压、空腹血糖、甘油三酯、空腹胰岛素呈正相关(P＜0.05);血清脂联素与空腹血糖、高密度脂蛋白胆固醇、空腹胰岛素、血肌酐呈正相关.结论 脂联素和vaspin均与糖尿病肾病有一定相关性,血清脂联素水平随着糖尿病肾病进展不断升高,而vaspin则随糖尿病肾病的进展下降.     

Role of plasma activated protein C in atherosclerosis in type 2 diabetic nephropathy

Objective To investigate the relationship between plasma activated protein C (APC) and the development of atherosclerosis (AS), and illustrate the mechanism of AS in type 2 diabetic nephropathy. Methods A total of 30 non-dialysis patients of type 2 diabetic nephrology and 26 control subjects were enrolled. APC, soluble vascular adhesion molecular-1 (sVCAM-1), soluble endothelial cell protein C receptor (sEPCR) and soluble thrombomodulin (sTM) were assayed by ELISA. Carotid intima-media thickness (IMT) was measured by ultrasonography. Results APC levels were significantly decreased in type 2 diabetic nephropathy compared with that in controls [(2 865.99±571.38) ng/L vs (3 227.70±300.44) ng/L, P＝0.005]. APC levels had negative correlation with IMT, 24 h albuminuria, sEPCR, sVCAM-1, sTM (r＝-0.720, -0.402, -0.477, -0.437, -0.505, all P＜0.05). Significant difference were observed in different proteinuria groups and IMT groups by ANOVA analysis(P＜0.05). Conclusions In type 2 diabetic nephropathy patients, plasma APC is negatively correlated with severity and IMT. Decreased plasma APC may lead to high levels of inflammatory mediators and endothelial cell injury, which may involved in the occurrence and development of atherosclerosis in diabetic nephropathy.     

Urinary microRNA-29 correlates with urinary albumin in type 2 diabetes mellitus

ObjectiveTo investigate the possibility of urinary microRNA-29 (miR-29) as biomarker for diabetic nephropathy in patients with type 2 diabetes. Methods Sixty-one patients with type 2 diabetes were divided into 2 groups: diabetes with normoalbuminuria[n＝25, (58.88±11.75) years old] and diabetes with albuminuria[n＝36, (62.19±13.11) years old]. There were no significant differences in age and gender between groups. The contents of miR-29a, miR-29b and miR-29c in urine supernatant were determined by real-time quantitative PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. The laboratory parameters including urinary albumin excretion, serum creatinine, BUN, glycosylated hemoglobin, and blood lipids were collected, while retinopathy serves as non-invasive method to assess vascular fibrosis. Results There was no significant difference in glycosylated hemoglobin levels and duration of diabetes between two groups, while the diabetes with albuminuria group had lower estimated glomerular filtration rate (eGFR) (P＝0.001), had higher level of miR-29a, miR-29b and miR-29c in urine (P＝0.029, 0.032, 0.040) compared with diabetes normoalbuminuria group. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r＝0.284, P＝0.039) and miR-29b level (r＝0.275, P＝0.046), urinary miR-29b significantly correlated with BUN（r＝0.277, P＝0.031）in patients with type 2 diabetes. However, no correlation was found between miR-29a, miR-29b, miR-29c and other clinical parameters. Conclusion Urinary miR-29a and miR-29b correlates with urinary albumin in patients with type 2 diabetes, and it needs further exploration and evaluation for urinary miR-29 to serve as potential biomarker for diabetic nephropathy in type 2 diabetes.     

Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes

BACKGROUND Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis. Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease. Dickkopf-1, a negative regulator of Wingless, has been proven to participate in renal fibrosis, glucose metabolism, and inflammation. However, whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear.AIM To assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes.METHODS Seventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study. Diabetic individuals were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups based on their urinary albumin/creatinine ratios(UACRs). Clinical characteristics and metabolic indices were recorded. Serum Dickkopf-1 levels were determined by enzymelinked immunosorbent assay.RESULTS No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group. However, the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group(P = 0.017), and those in the macroalbuminuria group were the lowest. Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1 c level(r = 0.368, P 0.01) and estimated glomerular filtration rate(r = 0.339, P 0.01), but negatively correlated with diabetes duration(r =-0.231, P = 0.050), systolic blood pressure(r =-0.369, P = 0.001), serum creatinine level(r =-0.325, P 0.01), and UACR(r =-0.459, P 0.01). Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR(odds ratio = 0.627, P = 0.021).CONCLUSION Serum Dickkopf-1 levels are negatively associated with UACR. Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.     

Angiotensin receptor blockers in diabetic nephropathy: renal and cardiovascular end points

The activity of the renin-angiotensin-aldosterone system (RAAS) is elevated both in the circulation and in the renal tissue of diabetic and nondiabetic nephropathies. The increased RAAS activity plays an important role in the hemodynamic and nonhemodynamic pathogenetic mechanisms involved in kidney disease. Previous studies have demonstrated that albuminuria is not only a marker of glomerular lesions, but also a progression promoter, and finally a powerful predictor of the long-term beneficial effect of blood pressure-lowering therapy. Randomized crossover and parallel blind studies in patients with diabetic nephropathy have demonstrated that angiotensin II receptor blockers (ARB) induce favorable changes in systemic blood pressure, renal hemodynamics, and proteinuria similar to those induced by angiotensin-converting enzyme (ACE) inhibition. Studies have revealed the optimal renoprotective dose for some ARBs; however, additional dose titration studies are urgently needed to obtain the maximum benefit of this valuable new class of compounds. The combination of ARB and ACE inhibition is well tolerated and even more effective than monotherapy in reducing systemic blood pressure and albuminuria in diabetic nephropathy. In addition, dual RAAS blockade is safe and well tolerated. Impaired autoregulation of glomerular filtration rate (GFR); demonstrated with some blood pressure-lowering agents implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension depending of the level of blood pressure. ARB does not interfere with GFR autoregulation in hypertensive diabetic patients. In contrast to previous observational studies with ACE inhibition, long-term treatment with ARB has similar beneficial renoprotective effect on progression of diabetic kidney disease in hypertensive diabetic patients with ACE II and DD genotypes. ARB can prevent/delay development of diabetic nephropathy independently of its beneficial blood pressure-lowering effect in patients with type 2 diabetes and microalbuminuria. Recently, two landmark studies led to the following conclusion: "Losartan and Irbesartan conferred significant renal benefit in patients with type 2 diabetes and nephropathy. This protection is independent of the reduction in blood pressure it causes. The ARB is generally safe and well tolerated." A recent metaanalysis indicates that ARBs reduce cardiovascular events mainly because of reduction in first hospitalization for congestive heart failure in hypertensive type 2 diabetic patients with albuminuria. The studies mentioned here suggest that ARB represents a beneficial treatment of hypertension and proteinuria in incipient and overt diabetic nephropathy.