Renal outcomes in patients with type 2 diabetes with or without coexisting non-diabetic renal disease

Aims

We sought not only to determine the independent predictors of non-diabetic renal disease (NDRD) but also to investigate the impact of NDRD on renal outcomes in patients with type 2 diabetes who underwent renal biopsy and were followed-up longitudinally.

Methods

The present study was conducted by reviewing the medical records of 119 type 2 diabetic patients who underwent renal biopsy at Yonsei University Health System from January 1988 to December 2008.

Results

Renal biopsy findings declared that 43 patients (36.1%) had diabetic nephropathy alone, 12 (10.1%) had NDRD superimposed on diabetic nephropathy, and 64 (53.8%) had only NDRD. On multivariate analysis, the absence of diabetic retinopathy, higher hemoglobin levels, and shorter duration of diabetes were independent predictors of NDRD in these patients. During the follow-up period, end-stage renal disease (ESRD) developed in 33 patients (27.7%). On multivariate Cox regression, higher serum creatinine levels, higher systolic blood pressure, longer duration of diabetes, and the presence of diabetic nephropathy were identified as significant independent predictors of ESRD. When the presence of diabetic retinopathy was included in the multivariate model, higher serum creatinine levels, higher systolic blood pressure, and the presence of retinopathy were shown to be independent predictors of ESRD.

Conclusions

Since diabetic patients with NDRD have significantly better renal outcomes compared to patients with biopsy-proven diabetic nephropathy, it is important to suspect, identify, and manage NDRD as early as possible, especially in type 2 diabetic patients with short duration of diabetes and those without diabetic retinopathy or anemia.     

2型糖尿病伴肾脏病变患者肾活检指征探讨

目的 研究2型糖尿病(DM)伴肾脏病变怀疑合并非糖尿病肾病(NDN)患者肾活检的指征及临床特征.方法 对53例2型糖尿病患者[因①急性肾衰竭7例;②突出的肾小球源性血尿6例;③糖尿病病程＜5年而蛋白尿＞0.5 g/24h者29例;④糖尿病病程＞5年、大量蛋白尿而血压正常者(肾活检指征)11例]行肾活检、眼底和常规实验室检查.24例因其他原因肾活检、住院期间发现2型糖尿病的患者做对照.结果 糖尿病肾病(DN)占51%,非糖尿病肾病占49%,其中系膜增生性肾炎最多见占1/3.病程越长,糖尿病肾病发生率越高;伴有糖尿病眼部病变[糖尿病视网膜病、白内障、晶体或(和玻璃体)浑浊]者肾活检均为糖尿病肾病.非糖尿病肾病患者糖尿病眼部病变少,糖尿病肾病病程短.肾活检指征②非糖尿病肾病的检出率最高(83.3%),指征④最低(18.2%).结论 糖尿病眼部病变预测糖尿病肾病的特异性为100%;2型糖尿病合并非糖尿病肾病患者血尿突出,糖尿病病程短,糖尿病眼部病变少见.     

2型糖尿病非糖尿病性肾病流行病学及病理变化研究

65例 2型糖尿病患者肾活检发现, 46. 2% (30 /65)有非糖尿病性肾病 (NDRD)。与糖尿病肾病对比,NDRD男性多见、病程短,浮肿、蛋白尿明显,系膜细胞增生及免疫球蛋白沉积显著,病理组织学类型多样,多见的是IgA肾病(占 43. 3% )。     

2型糖尿病患者非糖尿病肾脏疾病的患病率分析

目的 鉴别2型糖尿病患者蛋白尿的肾脏病因,估算非糖尿病肾病的患病率.方法 回顾性研究分析46例2型糖尿病合并肾损伤的患者,比较病史、心脏彩超、颈动脉多普勒彩超、眼底检查结果、肾小球滤过率、肝功能、肾功能、血脂、血糖、HbA1c、尿蛋白等临床指标,所有患者通过肾脏穿刺明确诊断,根据病理结果分为糖尿病肾病组和非糖尿病肾病组.结果 46例患者确诊糖尿病肾病比例占47.8%,52.2%患者是糖尿病合并其他肾小球疾病,即非糖尿病.肾病,在非糖尿病肾病组中以局灶节段肾小球硬化比例最高.糖尿病肾病组空腹血糖较高(P<0.05).心脏彩超各项指标中,糖尿病肾病组的射血分数显著低于非糖尿病肾病组(P<0.05).颈动脉彩超检测中发现,糖尿病肾病组存在动脉粥样斑块患者显著高于非糖尿病肾病组,其颈动脉内膜中层厚度均较非糖尿病肾病组高(P<0.05).值得注意的是,非糖尿病肾病与糖尿病视网膜病变关系不大,糖尿病视网膜病变对诊断糖尿病肾病具有较高的敏感性(72.2%)和特异性(91.7%,P<0.01).结论 2型糖尿病合并有蛋白尿时,空腹血糖、心脏射血分数、颈动脉粥样斑块和内膜中层厚度,以及眼底的改变作为临床鉴别糖尿病肾病和非糖尿病肾病的参考指标,肾活检则是明确糖尿病伴肾脏病变性质的重要手段.     

Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes

AIM:To evaluate the correlation between nonalcoholic fatty liver disease(NAFLD) and microvascular complications in type 2 diabetes mellitus(T2DM).METHODS:Data were obtained from 1217 inpatients with T2DM(757 females,460 males;aged 63.39 ± 12.28 years).NAFLD was diagnosed by hepatic ultrasonography.Diabetic nephropathy(DN),diabetic peripheral neuropathy(DPN),and diabetic retinopathy(DR) were diagnosed according to their respective criteria.The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression,respectively.RESULTS:Approximately 61% of inpatients with T2DM in Qingdao,China had NAFLD,which decreased significantly with increase in age and prolonged course of diabetes.The prevalence of NAFLD in patients presenting with DN,DPN and DR was 49.4%,57.2% and 54.9%,respectively.These rates were significantly lower than those of patients without DN,DPN and DR(65.9%,65.6% and 66.1%,respectively,P < 0.05).Participants with NAFLD had greater body weight,waist circumference(WC),body mass index(BMI),fasting blood glucose(FBG),hemoglobin A1c,alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,blood pressure,as well as triglyceride(TG) levels and lower high-density lipoprotein(HDL) concentration than those without NAFLD(P < 0.05).NAFLD was positively correlated with BMI,WC,TG,FBG,diastolic blood pressure,and systolic blood pressure but negatively correlated with the duration of diabetes,DR,DPN,DN,and HDL.CONCLUSION:Despite the benign nature of NAFLD,efforts should be directed toward early diagnosis,intensive blood glucose and blood pressure control,and effective dyslipidemia correction.     

Immunoglobulin G levels can predict non-diabetic renal disease in patients with type 2 diabetes mellitus

Background: Proteinuria in patients with diabetes mellitus (DM) is sometimes caused by glomerular diseases other than diabetic nephropathy. In patients with type 2 DM (T2DM), specific predictors for non‐diabetic renal disease (NDRD) are needed in addition to the traditional indicators for renal biopsy. Methods: From 1 January 2000 to 31 March 2011, we retrospectively enrolled 54 T2DM patients with proteinuria who had undergone renal biopsies into the present study. Associations between NDRD and 20 potential biomarkers, including serum levels of Igs and proteins associated with kidney function, and urinary protein and red blood cell levels, and hepatitis virus carrier status, were analyzed by multivariate logistic regression. Results: Multivariate logistic regression showed that reduced serum IgG (odds ratio [OR] 0.997; P = 0.006; 95% confidence interval [CI] 0.94–0.998) and creatinine (Cr; OR 0.587; P = 0.014; 95% CI 0.348–0.897) were predictors of NDRD. The area under the receiver operating characteristic curve (AUC_ROC) confirmed the good discriminatory power of IgG (AUC_ROC 0.857 ± 0.058; 95% CI 0.744–0.970; P < 0.001) and Cr (AUC_ROC 0.838 ± 0.054; 95% CI 0.732–0.943; P < 0.001). The IgG level below which the risk for NDRD increased, as calculated by obtaining the best Youden index, was 919.5 mg/dL (sensitivity 91.7%; specificity 83.3%), and the corresponding Cr level was 4.1 mg/dL (sensitivity 58.3%; specificity 96.7%). Conclusion: Serum IgG levels <919.5 mg/dL and serum Cr levels <4.1 mg/dL are associated with NDRD in T2DM patients.     

Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Lack of association between anemia and renal disease progression in Chinese patients with type 2 diabetes

Aims/Introduction

Anemia has a close interaction with renal dysfunction in diabetes patients. More proof is still awaited on the relationship between anemia and the progression of renal disease in this population.

Materials and Methods

In the present longitudinal study, 1,645 Chinese type 2 diabetes patients without end‐stage renal disease were included in the analysis in Nanjing, China, during January 2006 and December 2012. All patients were managed by staged diabetes management protocol, and clinical parameters were collected at each visit. The end‐point of progression of renal disease was evaluated during the follow up. Cox regression analysis was used to estimate the risk of anemia on renal disease progression.

Results

On recruitment, 350 (21.3%) patients had anemia, which was more common among those with older ages, longer diabetes duration, lower estimated glomerular filtration rate or more albuminura. On median follow up of 49 months (range 28–62 months), 37 patients (2.2%) developed the defined renal end‐point. Compared with those without anemia, patients with anemia had a higher risk of renal disease progression. However, multivariate analysis showed that anemia lost its statistical significance once estimated glomerular filtration rate was added into the model. Although the incidence of renal disease progression markedly increased by anemia status in patients of estimated glomerular filtration rate <60 mL/min/1.73 m², anemia was still not an independent risk factor for renal disease progression in this subgroup.

Conclusions

Anemia was a common finding in Chinese type 2 diabetes patients. Anemia was a risk factor for renal disease progression, but lost its significance once baseline renal function was adjusted.     

血清对氧磷酯酶活性变化与糖尿病视网膜病变的关系

目的 探讨对氧磷酯酶(PON)活性变化与2型糖尿病视网膜病变(DR)的关系。方法 用分光光度法检测96例DR患者、82例单纯2型糖尿病(DM)患者及58例正常对照者血清PON的活性；用放免法检测血清免疫反应性胰岛素(IRI)、C肽(C—P)的水平。结果 (1)DR患者血清PON活性明显低于DM患者(F＝11．04，P＜0．01)，DM患者血清PON活性低于正常对照者(F＝16．90，P＜0．01)；(2)PON活性与空腹血清胰岛素及C—P水平无明显相关(r＝0.113，P＞0．05，r＝0．109，P＞0．05)；(3)Logistic回归分析表明，PON活性(P＜0．01)是DR的独立变异危险因素。结论 PON活性变化与DR的发病有关。     

Serial renal biopsies in normo- and microalbuminuric patients with type 2 diabetes demonstrate that loss of renal function is associated with a reduction in glomerular filtration surface secondary to mesangial expansion

Aims

The aim of the present study was to explore the relationship between changes in renal structure in patients with type 2 diabetes at an early stage of diabetic nephropathy using serial renal biopsies, and change in renal function.

ApoE基因多态性与中国人2型糖尿病及其肾病并发症的关系

目的　研究 Apo E基因多态性与中国人 2型糖尿病及其肾病并发症的关系。方法　以载脂蛋白 E(Apo E)基因为候选基因 ,运用聚合酶链反应——限制性片段长度多态性 (PCR- RFL P)方法检测了 2 6 5例 2型糖尿病患者 ,其中未合并肾病者 10 6例 ,合并肾病者 15 9例 ,后者又分为蛋白尿者 12 2例 ,肾功能不全者 37例及 110例非糖尿病对照者的Apo E基因型。结果　 12型糖尿病合并肾病组与 2型糖尿病未合并肾病组相比 ,等位基因 ε2频率显著升高 (P=0 .0 0 894 ) ;基因型 E2 (E2 / 2 E2 / 3)组频率也显著升高 (P=0 .0 0 194 )。 2 2型糖尿病组与非糖尿病对照组相比基因型频率及等位基因频率均无显著性差异 (均 P>0 .0 5 )。结论　Apo E等位基因 ε2可能是 2型糖尿病合并肾病的危险因子。Apo E基因多态性与中国人 2型糖尿病发病无相关性     

Plasma homocysteine is associated with nonproliferative retinopathy in patients with type 2 diabetes without renal disease

Background and aimsThis study aimed to assess the role of plasma homocysteine (Hcy) in the development of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes (T2DM) without chronic kidney disease.MethodsThis was a cross-sectional study that included 94 T2DM. Hcy, serum 25-hydroxy (25-OH) vitamin D, vitamin B12, and folate were determined by the CMIA method. NPDR was determined according to the EURODIAB retinal photography methodology and optical coherence tomography (OCT) of the macula.ResultsCompared to patients without NPDR, patients with NPDR had longer diabetes duration (p < 0.001), higher Hcy (p < 0.001), lower vitamin B12 (p = 0.028) and lower estimated glomerular filtration rate (eGFR) (p = 0.004). NPDR was positively associated with diabetes duration (p < 0.001), HbA₁c (p = 0.049) and Hcy (p < 0.001), and negatively with vitamin B12 (p = 0.027) and eGFR (p = 0.005). Logistic regression analyses showed that diabetes duration (OR = 1.13, p < 0.001), Hcy (OR = 1.06, p = 0.047), and eGFR (OR = 0.96, p = 0.004) were the main predictors of NPDR in T2DM. Stepwise regression analyses showed that the best model for predicting Hcy (R2 = 0.104) included vitamins B12 and D.ConclusionsHigher Hcy is associated with NPDR and may play a role as a risk factor for its development in T2DM. Vitamins B12 and D seem to modify this association.     

Determinants of end-stage renal disease in Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria

Summary To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio ≥0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61% 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61 %) than in Caucasians from Rochester, Minnesota (17%) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease.     

2型糖尿病尿白蛋白排泄和视网膜病变相互关系研究

目的了解老年２型糖尿病（２ＤＭ）患者尿白蛋白排泄（ＵＡＥ）与视网膜病变（ＤＲ）之间的关系。方法对２４３例老年２ＤＭ患者同时进行了２４ｈＵＡＥ测定、眼底检查和详细的临床资料分析。结果①ＤＲ的发生率随ＵＡＥ的增加而增加,正常、微量和大量白蛋白尿患者,ＤＲ的发生率分别为１１７％、７６０％和８３３％,增殖性ＤＲ发生率分别为１８％、１４７％和３６７％;同样,白蛋白尿的发生率亦随ＤＲ的出现和进展而明显增高;②有白蛋白尿,但不伴ＤＲ的患者,其白蛋白尿常由其他非糖尿病性疾病所致。结论老年２ＤＭ患者ＵＡＥ与ＤＲ的发生密切相关,ＤＲ的存在与否对其白蛋白尿的病因有重要提示价值。     

Association of glutathione-S-transferase with patients of type 2 diabetes mellitus with and without nephropathy

Statements of the problemHyperglycemia induced oxidative stress is implicated as a contributor to the onset and progression of type 2 diabetes mellitus (T2DM) and its complications like diabetic nephropathy (DN). Glutathione-S-transferase (GST) is primarily involved in the neutralization of reactive oxygen species (ROS) by enzymatic conjugation with the scavenger peptide glutathione (GSH). Therefore, present study was aimed to evaluate the role of GST along with oxidative stress markers and their correlation in patients with Type 2 diabetes mellitus with and without nephropathy.MethodsThis study comprised of 300 participants divided into three groups of 100 each: healthy controls (HC), T2DM without complications and DN. Plasma GST, malondialdehyde (MDA), reduced GSH levels and ferric reducing ability of plasma (FRAP) were estimated spectrophotometrically.ResultsHighest GST levels was observed in T2DM which was significantly higher (p < 0.05) as compared to DN and HC. However, GSH and FRAP levels were found to be significantly lowest whereas MDA levels were significantly highest in DN as compared to T2DM and HC. GST showed a significant negative correlation with GSH, FRAP and positive correlation with MDA in both patients groups.ConclusionsHighest activity of GST in T2DM might be as a compensatory mechanism in response to oxidative stress. GST is found to have significant negative association with decreased GSH. Altered redox milieu in DN collectively conspire to increase the risk of renal damage in T2DM.     

高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点

目的：制备发病过程类似人类2型糖尿病的动物模型，并观察其肾脏病变特点。方法：用高糖高脂饲料喂养Wistar大鼠诱发胰岛素抵抗，然后用亚致病剂量链脲佐菌素（STZ）腹腔注射，诱发高血糖症。结果：高糖高脂饮食后1个月，大鼠发生高胰岛素血症、胰岛素抵抗和高脂血症。注射STZ后，大鼠血糖升高，平均279mg/dl，血胰岛素降至常规饲料喂养大鼠的水平。其肾脏改变特点，临床上表现为持续蛋白尿；病理改变为肾小球体积增大、髓袢腔扩张、系膜增生和硬化、基底膜增厚、内皮细胞泡沫样变、出入球动脉透明样变以及间质血管损伤等。结论：Wistar大鼠用高糖、高脂饮食结合小剂量STZ注射可成功制备2型糖尿病模型，并具有典型糖尿病肾病病变特点，是研究2型糖尿病及其慢性血管并发症的理想动物模型。     

2型糖尿病患者参考范围甲状腺激素与糖尿病肾病的相关性分析

目的:探讨甲状腺功能正常的2型糖尿病患者甲状腺激素与血糖控制及糖尿病肾病(diabetic kidney disease,DKD)的关系.方法:收集240例年龄≥45岁甲状腺功能正常的2型糖尿病患者临床及实验室资料,分析甲状腺激素与血糖控制及DKD的关系.结果:糖化血红蛋白(hemoglobin A1c,HbA1c)分...     

血清同型半胱氨酸水平与老年2型糖尿病视网膜病变的关系

目的　探讨血清总同型半胱氨酸 (Hcy)水平与老年人 2型糖尿病视网膜病 (DR)的关系及与其他危险因素的关系。方法　用免疫化学发光法检测 54例老年 2型糖尿病患者和 2 0例非糖尿病对照者的血清 Hcy水平 ,并收集其他相关危险因素资料。结果　 (1 )单因素分析结果显示 :DR组 (2 4例 )糖尿病病程、血浆糖化血红蛋白 (Hb A1 C)、血清甘油三酯 (TG)和 Hcy水平明显高于 2型糖尿病无视网膜病组 (NDR) (30例 )和非糖尿病对照组 (P<0 .0 5) ;(2 )血清 Hcy水平与 Hb A1 C呈正相关 ,与空腹胰岛素 (FINS)水平呈负相关 (P<0 .0 5) ;(3)多元 Logistic回归分析表明 ,血清Hcy水平增高是老年 DR的独立变异危险因素。结论　血清 Hcy水平增高与老年 DR的发病有关。