糖尿病合并骨质疏松与糖尿病微血管并发症的相关性研究

糖尿病(diabetes mellitus,DM)合并骨质疏松(osteoporosis,OP)和糖尿病微血管病变均是糖尿病的慢性并发症,由于发病的隐匿性,常常不被重视。随着人口老龄化程度的增加及医疗诊断水平的提高,糖尿病合并骨质疏松和DM微血管并发症的发病率及检出率呈现逐年上升趋势,近年来相关的研究也开始被广泛开展。糖尿病微血管病变及骨血流量减少可能导致骨量丢失和骨脆性增加,且微血管并发症的出现是DM患者骨量减少的临界因素。因此积极探讨DM合并骨质疏松与DM其他慢性微血管并发症之间的相关性,有助于早期对DM患者的不良结局进行综合性防范,改善患者预后。本文就糖尿病肾病(diabetic nephropathy,DN)、糖尿病视网膜病变(diabetic retinopathy,DR)、糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)以及糖尿病足(diabetic foot,DF)与糖尿病合并骨质疏松症(diabetic osteoporosis,DOP)的相关性研究作一综述。     

糖尿病肾病与糖尿病视网膜病变的相关性研究进展

糖尿病肾病(DN)和糖尿病视网膜病变(DR)均是糖尿病的微血管病变，是目前成人终末期肾病(ESRD)和致盲的重要原因，两者在发生、发展过程中具有一定平行性，又存在不平行性。DN和DR可预测彼此的发生、发展，但目前对于两者之间的关系尚未明确。因此，本文就DN与DR之间的相关性的研究进展作一综述，为临床诊断治疗提供帮助。     

2型糖尿病伴发非糖尿病性肾小球病变20例分析

糖尿病肾病是糖尿病的远期并发症之一,是糖代谢紊乱所致肾脏微血管病变的结果,具有独特的病理和临床特点.蛋白尿是糖尿病肾病(DN)最常见的临床表现之一 ,但是并非所有出现蛋白尿或者肾脏损害的糖尿病患者均属于DN.随着肾活检的开展,人们逐渐发现部分糖尿病患者的肾脏病变与糖尿病无关,而部分患者可以在糖尿病肾病的基础上同时合并其他的肾脏疾病,这就是所谓的糖尿病合并非糖尿病性肾脏疾病(NDRD).NDRD与DN 在病变性质,临床表现、治疗方法及预后均存在差异,本文通过对本院肾脏科近5年收治的2 0例NDRD患者的临床特点分析,以求提高对DM患者出现肾脏损害时的诊断与鉴别诊断水平, 为这类患者提供有效的诊治方案.     

黄葵胶囊联合丹参川芎嗪治疗糖尿病肾病的疗效观察

糖尿病肾病是糖尿病的严重并发症之一，其主要原因是肾动脉硬化和肾微血管病变引起的肾小球硬化，临床主要表现为大量蛋白尿。本科采用黄葵胶囊联合丹参川芎嗪注射液治疗糖尿病肾病，在减少尿蛋白方面取得一定疗效。现报道如下。     

2型糖尿病合并非糖尿病性肾脏疾病研究现状及进展

早在1936年，Kimmelestiel和Wilson等就首先报道了糖尿病患者所特有的肾脏损害，它是由于糖尿病本身的病情进展而累及肾脏微血管病变所致，故定名为糖尿病肾病（diabetic nephropathy，DN）。2007年发布的KDOQI系列临床实践指南中第一次提出了DKD（diabetic kidney disease），且指出术语“糖尿病肾病”（DN）应该被“糖尿病肾脏疾病”（DKD）取代。     

刘玉宁教授治疗糖尿病肾脏病经验

糖尿病肾脏病（DKD）是糖尿病性微血管病变所引起的肾小球硬化症,是糖尿病的严重并发症之一。中医称糖尿病为消瘅或消渴病,DKD为消渴病肾病。DKD不仅是发达国家终末期肾病的首要病因,也是我国目前最常见的继发性肾脏病之一。该病发病率高、病情进展快、治疗难度大且预后较差,成为严重影响人类生存质量的重大问题。全国著名中西医结合肾病专家刘玉宁教授,从医四十余年,长于肾脏病的诊治,     

低分子肝素治疗糖尿病肾病的临床分析

糖尿病肾病是糖尿病的严重微血管病变,是导致终末期肾功能衰竭的主要原因之一。糖尿病肾病患者血液多呈高凝状态,肾小球内凝血、血栓形成,导致肾功能衰竭进展加剧。我院应用低分子肝素治疗糖尿病肾病,改善肾小球内高凝状态,修复肾小球基底膜电荷屏障,明显延缓糖尿病肾病的病程进展。     

糖尿病肾病的发病机制及治疗进展

糖尿病肾病是糖尿病严重的微血管并发症之一,是终末期肾病的主要原因.近年来的研究发现糖尿病肾病的发病机制涉及多方面因素,其中对炎症、免疫因素及细胞因子等的研究越来越多,同时也为治疗糖尿病肾病提供了新的方向.     

红花注射液联合缬沙坦治疗糖尿病肾病52例疗效观察

糖尿病肾病是糖尿病主要的微血管病变之一，是糖尿病患者的重要死亡原因。我们于2002年1月-2005年6月应用红花注射液联合缬沙坦治疗糖尿病肾病，其对早、中期糖尿病肾病有较好的疗效，现报道如下。     

糖尿病性视网膜病变的研究进展

糖尿病性视网膜病变(diabtic retinopathy,DR)是糖尿病常见的微血管并发症,是目前世界上四大主要致盲病因之一,其发病率随病程发展而增加,如同时全身合并有高血压、高血脂、血流变学有明显改变者,则发生率更高.流行病学调查表明,大约有75%不重视血糖控制的糖尿病患者,在发病15年内发生糖尿病性视网膜病变.在糖尿病患者中,发生糖尿病视网膜病变者,达50%以上.因其高发病率、高致残率,给病人及其家属带来严重的经济、心里及其社会负担,现将糖尿病性视网膜病变的病因、危险因素、发病机制、临床表现、诊断及其预防治疗进行归纳总结,以便更好的指导临床实践.     

Results of Kidney Transplantation for Diabetic Nephropathy: A Single-Center Experience

In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome.     

Resolution of Early Stage Diabetic Nephropathy in an Obese Diabetic Patient after Gastric Bypass

Epidemiological studies have proven that obesity is a significant risk factor for type 2 diabetes. Long-term progression of diabetes leads to various microvascular complications, of which diabetic nephropathy has become of increasing importance, and is the main cause of end-stage renal failure in occidental countries. Microalbuminuria is the first marker of incipient diabetic nephropathy, an early stage glomerulopathy which can progress to renal failure and which historically has been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. We report a severely obese diabetic patient on treatment for diabetic nephropathy with ACE-inhibitors and poor results, which resolved after Roux-en-Y gastric bypass.     

Polyphenolic Extract of Ichnocarpus Frutescens Attenuates Diabetic Complications in Streptozotocin-Treated Diabetic Rats

Diabetic nephropathy is one of the major complications of diabetes. Oxidative stress is implicated as an important mechanism by which diabetes causes nephropathy. The aim of the study was to examine the involvement of oxidative stress in the progression of nephropathy in STZ diabetic animals and to evaluate the potential of polyphenolic extract (PPE) in the treatment of diabetes mellitus. In this study, we examined whether prolonged oral administration of polyphenolic extract of Ichnocarpus frutescens could prevent the progress or improve the outcome of diabetic nephropathy induced by oxidative stress in STZ diabetic rats. Intraperitoneal glucose tolerance test (IPGTT) revealed a significant decrease in blood glucose levels at 180 min after glucose loading in Wistar albino rats fed with PPE. During the eight weeks of experimental period, diabetic rats exhibited wide range of symptoms, including loss of body weight, hyperglycemia, polyuria, proteinuria, renal enlargement, and total renal dysfunction. A significant increase in TBARS level was observed in diabetic kidney, which was accompanied by a significant decrease in enzymatic and non-enzymatic antioxidant levels. After eight weeks, PPE-treated groups showed a lower level of blood glucose compared with non-treated STZ diabetic rats. The increases in urinary albumin and protein after eight weeks of treatment were significantly inhibited by prolonged treatment with PPE. In addition, PPE attenuates the adverse effects on hepatic biomarkers. We found that PPE can effectively protect against aldose reductase activity and protein damage (albumin glycation), and showed that its action was mainly due to enriched polyphenolic content. Our results also showed that treatment with PPE normalized the increase in hyperalgesia (i.e., the response to thermal stimuli) associated with the induction of diabetes by STZ. PPE administration in diabetic rats clearly ameliorated diabetic complications, suggesting not only a natural antioxidant but also supportive therapy for the treatment of type II diabetes.     

Diabetic nephropathy-pathophysiology and management

Diabetes mellitus is the leading cause ofend-stage renal disease in the United States. Between 1996 and 2001, the prevalence ofdiabetes in the Medicare population increasedby 31%. Patients with diabetes account forapproximately one-third of all cases ofend-stage renal disease (ESRD). This number isexpected to rise dramatically as a result ofthe growing incidence of diabetes and the agingpopulation. A major complication of diabetesincludes end-stage renal disease as a resultfrom diabetic nephropathy. The earliestclinical evidence that nephropathy exists isthe appearance of low, yet abnormal, levels ofalbumin in the urine, referred to asmicroalbuminuria. This can progress toproteinuria representing overt diabeticnephropathy. Prevention remains the best way toreduce mortality and maintain a high quality oflife in these individuals as recent clinicaltrials confirm that it is possible to not onlyslow down the progression of diabeticnephropathy, but even prevent it from becominga significant problem. This article reviewsthe pathogenesis, diagnostic screening, andtreatment strategies of diabetic nephropathy.     

Genetic Determination of TNF and Myeloperoxidase Production in Dialyzed Patients with Diabetic Nephropathy

Introduction: Diabetic nephropathy accounts for more than 20% of the cases of chronic renal failure. For many patients, the method of renal replacement therapy is chronic ambulatory peritoneal dialysis (CAPD). Diabetes, through glucose auto‐oxidation and production of free radicals, causes protein glycation. Products of protein glycation increase the concentrations of proinflammatory cytokines. The tumor necrosis factor (TNF) is one of the most important cytokines of cellular response and inflammation. Its level is increased in chronic renal failure. Numerous polymorphisms have been identified within and around the TNF gene, which is located on chromosome 6. Single nucleotide polymorphisms, such as a polymorphism at a position ? 308, probably have a direct influence on the TNF production. Myeloperoxidase (MPD) is a heme enzyme, participating in oxygen mechanisms of microorganism killing by phagocytes. Chronic renal failure patients show a significant reduction in the intracellular myeloperoxidase level. In the promoter region of myeloperoxidase gene, at position ? 463, G to A transition has been found, which causes a decreased gene expression. The aim of the present study was an analysis of genetic basis of TNF and myeloperoxidase production in dialyzed patients with diabetic nephropathy. Subjects and Methods: The study group consisted of 37 diabetic nephropathy patients treated with peritoneal dialysis. The control subjects were 58 dialyzed patients with other primary renal diseases and 115 healthy individuals. TNF and myeloperoxidase gene polymorphisms were detected by polymerase chain reaction (PCR) and amplification products were digested with the NcoI and AciI restriction enzymes respectively. ELISA determined the TNF and MPO levels in plasma. Results: We haven't found significant differences in TNF genotype and allele frequencies between the groups; however, diabetic nephropathy patients seemed to have a lower frequency of TNF1/TNF1 genotype. In diabetic nephropathy patients, the median TNF plasma level was 43.8 pg/mL, and in other renal diseases it was 36.8 pg/mL. The difference was significant (p < 0.05). The differences in TNF levels between both groups and the control group (1.7 pg/mL) were highly significant (p < 0.001). There was a statistically significant difference in MPO genotype frequencies between patients with diabetic nephropathy and patients with other renal diseases (p < 0.05). GG and AA genotypes were significantly more common in patients with diabetic nephropathy. The genotype distribution in patients with other renal diseases was similar to the distribution in the control group. Median plasma MPO level in diabetic nephropathy patients was similar to patients with other renal diseases. A significantly lower level (p < 0.05) was observed in the control group. In diabetic nephropathy, we have also observed a correlation between the MPO genotype and an earlier onset of the disease. For the TNF genotype, we haven't found such a relationship. There was also no relationship between the TNF and MPO genotypes and time to end‐stage renal disease (ESRD). There were no differences in the frequency of peritonitis between patients with diabetic nephropathy and dialyzed patients with other renal diseases. Discussion: In conclusion, we found that in diabetic nephropathy patients molecular variants of TNF are more frequent than in nondiabetic patients with chronic renal failure and these changes might be associated with altered ability to TNF synthesis. Analysis of the myeloperoxidase genotypes showed significant difference in genotype distribution in dialyzed patients with diabetic nephropathy. This, however, requires further studies to confirm the relationship with the disease.     

Association of genetic variants with diabetic nephropathy

Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, e NOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.     

早期糖尿病肾病的危险因素分析

目的:探索早期糖尿病肾病(DN)的危险因素,为临床防治早期DN提供参考依据。方法:多中心收集早期DN 182例(A组),以170例单纯糖尿病(DM,B组)为对照,收集年龄、病程、血压及腰臀比(WHR),检测血脂、糖化血红蛋白(HbA1c)及尿白蛋白(uAlb),计算尿白蛋白排泄率(UAER),进行统计学分析。结果:(1)两组比较:病程、SBP、DBP、WHR、HbA1c、TG、HDL、UAER差异有统计学意义(P<0.05,P<0.01),LDL、TC差异无统计学意义(P>0.05)。(2)以UAER为因变量,其他指标为自变量,进行logistic分析。其中病程、SBP、WHR、HbA1c先后被列入方程,为早期糖尿病肾病的独立危险因素(P<0.01)。(3)spearman相关分析显示:HbA1c与病程、TG,WHR与TG、HbA1c呈正相关(P<0.05)。结论:糖尿病病程、收缩压、腰臀比、糖化血红蛋白是早期DN的独立危险因素,严格控制血糖血压、减肥有利于延缓糖尿病肾病的进展。     

Genetic susceptibility to nephropathy in Pima Indians with type 2 diabetes mellitus

Summary: In Pima Indians, the incidence of end-stage renal disease, nearly all of which is attributable to type 2 diabetes mellitus, is more than 20 times that in the general United States population. Studies in the Pimas indicate that factors other than diabetes per se enhance susceptibility to the development of diabetic nephropathy. Aggregation of renal disease in families, a relationship between parental blood pressure and diabetic nephropathy in the offspring, and an association between higher prediabetic blood pressure and the occurrence of renal disease after the onset of diabetes all point to individual differences in susceptibility. Although clustering of environmental exposures may be responsible for these findings, they may also represent genetic transmission of susceptibility to renal disease. Recently, linkage analyses were performed in 98 diabetic sib-pairs, both affected by diabetic nephropathy. Two adjacent markers on chromosome 7 met the criteria for suggestive linkage with two-point analysis. Positioned between these markers is the gene coding for aldose reductase. Polymorphisms of this locus are associated with diabetic microvascular complications in other populations. Linkage studies provide evidence that familial aggregation of diabetic renal disease reflects, in part, genetic transmission of susceptibility that appears to be independent of the transmission of diabetes.     

Diabetic nephropathy in insulin-dependent patients.

Diabetic nephropathy is a serious complication of insulin-dependent diabetes mellitus (IDDM) that affects 30% to 40% of IDDM patients with a predictable time of onset. Epidemiologic data suggest that either a genetic susceptibility, perhaps for hypertension (HTN), or an environmental exposure selects out that subset of IDDM patients and destines them to develop diabetic nephropathy. Hopefully, assessing glomerular hyperfiltration, urinary albumin excretion rate (AER), glycemic control, mean arterial pressure (MAP), and perhaps early morphologic changes will allow early identification of this high-risk group of IDDM patients before overt nephropathy is present. Once nephropathy appears, renal function inexorably declines, although the natural history of this progression may be changing with earlier therapeutic intervention. IDDM patients with nephropathy suffer a high mortality rate compared with IDDM patients without nephropathy or with nondiabetic end-stage renal disease patients. This is primarily due to malignant atherosclerotic disease manifested as coronary, peripheral, and cerebral arterial disease. Therapeutic interventions of demonstrated benefit in slowing the rate of decline of glomerular filtration rate (GFR) include blood pressure control and low-protein diets. Strict blood sugar control or treatment with aldose reductase inhibitors, converting enzyme inhibitors (CEIs), or inhibitors of advanced glycosylation end-product formation are of possible benefit, but are awaiting clinical trial results.     

Routine Coronary Angiography in Diabetic Nephropathy Patients Before Transplantation

We evaluated the incidence of significant coronary artery stenoses (CAS), angina pectoris (AP), revascularization and associated risk factors in 155 consecutive diabetic nephropathy transplant candidates. Kidney and kidney-pancreas transplant candidates with diabetes for more than 10 years and/or retinopathy and/or biopsy verified diabetic nephropathy were included. The inclusion period was 1999-2004. Seventy-two percent of patients were male. Sixty-one percent had type 1 diabetes and 39% had type 2 diabetes and mean age was 46 years (+/-10) and 58 years (+/-11), respectively. History of heart disease was present in 34% of patients, 34% had cerebro-vascular and/or peripheral atherosclerotic disease, and 51% had neither. Fifty-five percent had a smoking history and 46% were on dialysis. Significant CAS was found in 45% of patients, of whom 17% had AP. No patients below 35 years of age had significant CAS (n = 11, p = 0.001). Revascularization was performed in 57% of patients with significant CAS. The only risk factor for significant CAS in multiple logistic regression was age (p = 0.046). Approximately half of the patients had significant CAS, and half of these underwent revascularization. Most patients with CAS did not have symptoms of myocardial ischemia. The data justify screening diabetic nephropathy transplant candidates with coronary angiography before transplantation.