Non diabetic renal disease in type 2 diabetes mellitus

AIM: The aim of this analysis of renal biopsies in people with type 2 diabetes was to know the prevalence and nature of non-diabetic renal disease (NDRD) and to note its correlation with the duration of diabetes, extent of proteinuria and presence or absence of retinopathy. METHODS: From January 2000 to December 2004, 160 people with type 2 diabetes with clinically suspected NDRD underwent renal biopsy reported by a single pathologist. The case records of these patients were retrospectively analysed. Based on the biopsy findings, patients were grouped as Group I, isolated NDRD; Group II, NDRD with underlying diabetic glomerulosclerosis; and Group III, isolated diabetic glomerulosclerosis. The relation of histology with clinical profile in each group was noted and statistically analysed using strata 6 software. RESULTS: Of the 160 patients studied, 118 were males and 42 were females (2.8:1). The average age was 51.35 years (30-79). Indications for renal biopsy included: nephrotic syndrome in 55 (34.37%), acute renal failure (ARF) in 49 (30.62%), rapidly progressive renal failure (RPRF) in 24 (15%), absent retinopathy in 19 (11.87%), haematuria in 10 (6.25%) and acute on chronic renal failure (CRF) in three (1.87%) patients. Group I included 68 patients (42.50%), Group II included 48 patients (30%) and Group III included 44 patients (27.50%). The mean duration of diabetes was 5.37, 10.12 and 6.86 years in Groups I, II and III respectively. The duration of diabetes was significantly less in Group I compared with Group II and III combined (5.37 vs 8.53; P < 0.001). Diabetic retinopathy was absent in 61 (38.13%) patients, of whom 41 (67.21%) had isolated NDRD. The most common NDRD were acute interstitial nephritis (18.1%), post infectious glomerulonephritis (17.24%), membranous nephropathy (11.20%) and focal segmental glomerulosclerosis (7.75%). CONCLUSIONS: Prevalence of NDRD (either isolated or superimposed on underlying diabetic glomerulosclerosis) is very high in appropriate clinical settings. The shorter duration of diabetes and the absence of retinopathy, especially when associated with nephrotic proteinuria, strongly predict NDRD.     

Nephropathy in Type II diabetes

Summary: The incidence and prevalence of end-stage renal failure due to renal involvement in patients with type II diabetes has increased in the Western world and in Asia. Interesting differences of prevalence of this disease are found between nations. the reasons for the increase in the frequency of nephropathy in type II diabetes include: (i) an increasing prevalence of type II diabetes; (ii) ageing of the population; and (iii) improved survival of patients with type II diabetes. Today patients frequently live long enough to develop diabetic nephropathy. In contrast with previous opinion, no major differences in renal involvement is found between type I and type II diabetes. This applies to renal haemodynamics as well as renal histology, although non-specific changes, presumably of an ischaemic nature are more frequently found in patients with type II diabetes. the renal risk appears to be similar in type II diabetes (i.e. cumulative prevalence of proteinuria and rate of progression to renal failure).     

Diabetes mellitus and the risk of non-vertebral fractures: the Tromsø study

We wanted to determine the risk of non-vertebral fracture associated with type and duration of diabetes mellitus, adjusting for other known risk factors. This is a population-based 6-year follow-up of 27,159 subjects from the municipality of Tromsø, followed from 1994 until 2001. The age range was 25–98 years. Self-reported diabetes cases were validated by review of the medical records. All non-vertebral fractures were registered by computerized search in radiographic archives. A total of 1,249 non-vertebral fractures was registered, and 455 validated cases of diabetes were identified. Men with type I diabetes had an increased risk of all non-vertebral [relative risk (RR) 3.1 (95% CI 1.3–7.4)] and hip fractures [RR 17.8 (95% CI 5.6–56.8)]. Diabetic women, regardless of type of diabetes, had significantly increased hip fracture risk [RR 8.9 (95% CI 1.2–64.4) and RR 2.0 (95% CI 1.2–3.6)] for type I and type II diabetes, respectively. Diabetic men and women using insulin had increased hip fracture risk. Duration of disease did not alter hip fracture risk. An increased risk of all non-vertebral fractures and, especially, hip fractures was associated with diabetes mellitus, especially type I. Type II diabetes was associated with increased hip fracture risk in women only.     

高龄住院老年人中2型糖尿病与老年性骨折呈负相关-病例对照研究

目的：采用病例对照法初步分析2型糖尿病与老年性骨折的关系。方法根据纳入和排除标准筛选大于60周岁的住院糖尿病和非糖尿病病人,收集其人口学特征、病史和治疗情况,采用SAS 9.2软件建立logistic多元回归模型分析调整多种因素后2型糖尿病与老年性骨折的关系。结果共纳入150例病例,平均年龄82.39岁。女性（ OR：3.314,95％CI 1.191～9.218）和年龄（每增加5岁OR：1.399,95％CI 1.010～1.939）是老年性骨折的危险因素;调整年龄和性别等混杂因素的影响之后,患2型糖尿病和血管性痴呆的患者发生老年性骨折的风险更低,OR值分别为0.237（95％CI 0.072～0.787）和0.091（95％CI 0.015～0.742）。结论本研究提示在高龄住院老年人中2型糖尿病与老年性骨折呈负相关,其原因有待更大样本量的研究进行分析。     

Atherosclerotic cardiovascular disease among patients with type 2 diabetes in Basrah

AIM: To determine the frequency of atherosclerotic cardiovascular disease and its risk factors among patients with type 2 diabetes in Basrah, Iraq.METHODS: Participants in this cross-sectional study were patients who had type 2 diabetes for at least 1 year, presenting at the Al-Faiha Diabetes Endocrine and Metabolism Center in Basrah (Southern Iraq) over the period from January to December 2008.RESULTS: The series included 1079 patients (58.8% men), of whom 25.0% were smokers. The prevalence of symptomatic cardiovascular disease and hypertension was 16.0%, and 44.3% respectively. Those who were overweight or obese constituted 70.5%. Insulin was used in only 26.9% despite 56.1% having had diabetes for 6 years and more. The mean glycated hemoglobin (HbA1c) was 9.46% ± 2.0% and only 5.5% achieved the target of HbA1c of < 7%. We had 68.7% of patients with total cholesterol of ≥ 200 mg/dL, 21.5% with high density lipoprotein cholesterol of < 40 mg/dL, 84.1% with low density lipoprotein cholesterol of ≥ 100 mg/dL and 71.6% with triglyceride of ≥ 150 mg/dL.CONCLUSION: Among adults with type 2 diabetes mellitus, there was increased frequency of cardiovascular disease and its modifiable risk factors. This finding necessitated urgent work to modify these risk factors in a population based setting.     

Classification tree model analysis on related factors of different stages of kidney in type 1 diabetic patients

Objective To analyze the related factors of micro-albuminuria and macro-albuminuria in type 1 diabetes mellitus (DM) in the classification tree model, and to screen the high risk population of diabetic kidney disease. Methods 394 patients with type 1 diabetes were enrolled in the hospital from 2008 to 2015. According to glomerular filtration rates and urine albumin quantification, the patients were divided into type 1 diabetes group (299 cases), micro-albuminuria group (73 cases) and macro-albuminuria group (22 cases). The classification tree model was utilized to analyze related factors of the different stages of proteinuria, and the high-risk population was screened by node gain analysis. Results Four important explanatory variables were screened out by the classification tree model from the 27 candidate variables related to primary renal damage, including retinopathy, fibrinogen, waist-hip ratio (WHR), red blood cell distribution width (RDW). Retinopathy was an major factor of DKD. The probability of macro-albuminuria in retinopathy and WHR＞0.82 group was 43.8%, and if at the same time RDW＞0.14, the probability of macro-albuminuria was 88.9%. Conclusions The classification tree model can analyze factors of the separate stages of proteinuria in type 1 diabetic patients effectively. Retinopathy is the major influential factors of type 1 diabetic patients with proteinuria.     

Significance of age in the survival of diabetic patients after kidney transplantation

Background: In recent years acceptance ofdiabetic patients for renal replacement therapyhas increased. Renal transplantation for Type Idiabetic patients is widely accepted but theappropriate treatment for Type II diabeticpatients is still a matter of dispute. Ourstudy was done to determine whether the age ofType II diabetic patients constituted anadditional risk factor.Methods: We analyzed the outcome of renaltransplantation in 56 diabetic patients, 31Type I and 25 Type II diabetics (we excludedany who had combined kidney-pancreastransplants). We compared them with 51non-diabetic patients who were transplantedbecause of end-stage renal failure due tonephrosclerosis and age-matched to type IIdiabetic patients. We assessed the one- andthree-year patient and graft survival, thequality of renal function, the maincomplications and causes of mortality.Results: The overall one- and three-yearpatient survival was 69% and 60% in Type IIpatients; 73% and 69% in Type I diabetespatients and 88% and 80% in patients withnephrosclerosis. The overall one- andthree-year actuarial graft survival was 50%and 38% in patients with Type II disease and58% and 50% in Type I diabetes, and 76% and64% in nephrosclerosis. The main cause ofgraft loss in all groups was death (withfunctioning kidney) due to infections andcardiovascular complications.Conclusions: Diabetes itself is the mostimportant variable in patients who have poorresults after kidney transplantation.Increasing age increases slightly the risk forpoor graft and patient survival. Both groups ofdiabetic patients have poorer results thancontrols but in this comparison age was anindependent factor.     

Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes: a subanalysis of Japanese patients from the RENAAL study

Background The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study has previously shown losartan to confer significant benefits to patients with type 2 diabetes and nephropathy. The original study of 1513 patients included 96 Japanese patients; the present study is a post-hoc analysis of the effects of losartan in this Japanese subpopulation. Methods This double-blind, randomized study compared losartan (50 to 100 mg once daily) with placebo. The study medication was taken in addition to conventional antihypertensive treatment, and the mean follow-up period for the Japanese patients was 2.8 years. The primary endpoint was the composite of doubling of serum creatinine, endstage renal disease, or death. Secondary endpoints included changes in proteinuria levels. Safety was also evaluated. Results The primary composite endpoint was reached in fewer Japanese patients receiving losartan than placebo (50.0% versus 65.4%, respectively). The treatment effects of losartan were more robust when data were corrected for differences in proteinuria at baseline – a significant relative risk reduction of 45% with losartan (P = 0.0397) was apparent. Treatment benefit exceeded that attributable to blood pressure changes alone. Levels of proteinuria were reduced with losartan compared with placebo, with an overall losartan treatment effect of 37.8% (P < 0.001). Overall, losartan was similarly well tolerated in both the Japanese patients and the total population. Conclusions In Japanese patients with type 2 diabetes and nephropathy, losartan offers renal protection and is generally well tolerated.     

Ischaemia imaging in type 2 diabetic kidney transplant candidates--is coronary angiography essential?

BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death in type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is a high prevalence of silent CAD in these patients. Controversy exists regarding the role of dobutamine stress echocardiography (DSE) in detection of CAD. Our purpose was to compare DSE with coronary angiography (CA) for the detection of CAD in type 2 diabetic patients undergoing evaluation for renal transplantation. METHODS: Forty (36 male, four female) type 2 diabetic patients with end-stage renal disease (ESRD) were subjected to DSE followed by CA as a part of their pre-renal transplant evaluation. The ability of DSE to predict 70% stenosis in one or more coronary arteries as determined by CA was evaluated. Mean age of the patients was 49.2 +/- 5 years (range 39-60 years). RESULTS: DSE was positive in 10 (25%) patients, while 19 patients (48%) had a more than 70% lesion in at least one epicardial vessel on CA (six patients had single vessel, three had double vessel and 10 had triple vessel disease). The sensitivity and specificity in identifying CAD was 47.3 and 95.2%, respectively, while positive predictive value and negative predictive value was 90% and 66%. Accuracy of DSE was 72.5%. All four patients with diffuse diabetic coronary artery disease had negative DSE. CONCLUSION: DSE is a poor predictor of coronary artery disease in type 2 DM patients being evaluated for renal transplantation. CA should be included in evaluation of type 2 diabetic patients who are renal transplant candidates.     

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos

Aim:   The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus.
Methods:   A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method.
Results:   Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P  ≤ 0.044). In addition, female patients with macroalbuminuria without dialysis showed no significant differences with patients undergoing dialysis.
Conclusion:   The ACE DD genotype is a risk factor for the development of renal disease in Mexican Mestizo females with type 2 diabetes, indicating a possible DD genotype-associated sex effect in renal disease.     

Post-renal transplant diabetes mellitus--a retrospective study.

The prevalence of post-transplant diabetes mellitus in 222 consecutive live related renal allograft recipients over a 3-year period was found to be 11.7%. Most of them (20 of 26) developed diabetes mellitus within the first 4 months of transplantation. Post-transplant diabetic patients were older, and had a significantly greater incidence of avascular necrosis of bone. An assessment of risk factors showed that abnormal postprandial blood sugar pretransplant was a significant predictor for development of post-transplant diabetes, whereas cumulative oral steroid dose, weight gain after transplant, type of immunosuppression employed, and graft function were not important. We conclude that post-transplant diabetes mellitus frequently develops in patients with a predisposition by virtue of older age and pretransplant postprandial hyperglycaemia. While steroids are important in the pathogenesis, there was no demonstrable dose-response relationship; post-transplant diabetic patients may be a group with a greater propensity to steroid-induced complications.     

2型糖尿病患者合并非糖尿病性肾损害的临床病理分析

目的：了解2型糖尿病合并非糖尿病性肾损害的临床病理特点。方法：总结分析29例2型糖尿病合并非糖尿病肾损害的临床资料、病理改变及治疗反应。结果：2型糖尿病或糖尿病肾病可以合并多种非糖尿病肾损害,以各种类型的原发性及继发性肾小球疾病为主。原发性肾小球疾病常见病理类型有轻度系膜增生性肾小球肾炎、膜性肾病、IgA肾病和微小病变。这些患者具有以下不同于典型糖尿病肾病的特点：（1）糖尿病病程短于5年;（2）大量蛋白尿或肾功能不全时血压正常;（3）急性肾功能衰竭;（4）血尿明显。大部分肾病水平蛋白尿患者经糖皮质激素或糖皮质激素联合细胞毒类药物治疗后可完全缓解.结论：（1）2型糖尿病合并肾损害不等于糖尿病肾病;（2）2型糖尿病可以合并各种非糖尿病性肾损害;（3）当2型糖尿病伴肾脏受累者具有上述不符合糖尿病肾病特征时,应尽早行肾活检明确诊断;（4）在充分考虑患者 的临床特点、病理改变、严格控制血糖及血压的情况下,糖皮质激素或糖皮质激素联合细胞毒类药物治疗是安全有效的,可以改变患者的预后。     

Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes

Elevated plasma concentrations of TNF receptors 1 and 2 (TNFR1 and TNFR2) predict development of ESRD in patients with type 2 diabetes without proteinuria, suggesting these markers may contribute to the pathogenesis of renal decline. We investigated whether circulating markers of the TNF pathway determine GFR loss among patients with type 1 diabetes. We followed two cohorts comprising 628 patients with type 1 diabetes, normal renal function, and no proteinuria. Over 12 years, 69 patients developed estimated GFR less than 60 mL/min per 1.73 m(2) (16 per 1000 person-years). Concentrations of TNFR1 and TNFR2 were strongly associated with risk for early renal decline. Renal decline was associated only modestly with total TNFα concentration and appeared unrelated to free TNFα. The cumulative incidence of estimated GFR less than 60 mL/min per 1.73 m(2) for patients in the highest TNFR2 quartile was 60% after 12 years compared with 5%-19% in the remaining quartiles. In Cox proportional hazards analysis, patients with TNFR2 values in the highest quartile were threefold more likely to experience renal decline than patients in the other quartiles (hazard ratio, 3.0; 95% confidence interval, 1.7-5.5). The risk associated with high TNFR1 values was slightly less than that associated with high TNFR2 values. TNFR levels were unrelated to baseline free TNFα level and remained stable over long periods within an individual. In conclusion, early GFR loss in patients with type 1 diabetes without proteinuria is strongly associated with circulating TNF receptor levels but not TNFα levels (free or total).     

Incidence of proteinuria in type 2 diabetes mellitus in the Pima Indians

Little is known of the natural history of nephropathy in type 2 (non-insulin-dependent) diabetes, yet type 2 diabetes is a major cause of end-stage renal disease in the United States. The incidence rate of heavy proteinuria was determined in Pima Indians participating in a longitudinal population study of diabetes and its complications. Heavy proteinuria was defined by a urine protein (g/liter) to urine creatinine (g/liter) ratio greater than or equal to 1.0 (greater than or equal to 113 mg protein/nmol creatinine), a level which corresponds to a urine protein excretion rate of about 1 g/day. The incidence rates of proteinuria in diabetic Pimas were 4, 12, 37, and 106 cases/1,000 person-years at risk in the periods 0 to 5, 5 to 10, 10 to 15, and 15 to 20 years after the diagnosis of diabetes. The cumulative incidence rates were 2%, 8%, 23%, and 50% at 5, 10, 15, and 20 years, respectively. The duration of diabetes, severity of diabetes as determined by the degree of hyperglycemia and type of treatment, and blood pressure were risk factors for proteinuria. The presence of heavy proteinuria was strongly associated with the development of renal insufficiency, defined by serum creatinine greater than or equal to 2.0 mg/dl (greater than or equal to 177 mumol/liter). The incidence of proteinuria in type 2 diabetes in Pima Indians was as high as that reported in type 1 diabetes in other populations and represents a frequent, serious complication of the disease.     

Kidney transplantation in type 2 diabetic patients: a comparison with matched non-diabetic subjects.

BACKGROUND: Because they generally are older and frequently have co-morbidities, patients with type 2 diabetes mellitus and end-stage renal disease seldom are selected for renal transplantation. Thus, information on transplantation results from controlled studies in this high-risk category of patients is scarce. We have compared the results of kidney transplantations in type 2 diabetic patients with carefully matched non-diabetic subjects. METHODS: All first cadaveric renal transplants performed in type 2 diabetic patients from January 1, 1988 to December 31, 1998 in our centre were included. Non-diabetic controls were individually matched with diabetic patients with respect to year of transplantation, sex, age, selected immunological parameters, and graft cold ischaemia. RESULTS: We included 64 type 2 diabetic and 64 non-diabetic patients who were followed for a mean period of 37+/-27 and 41+/-31 months, respectively, after renal transplantation. Patient survival at 1 and 5 years post-transplant was 85 and 69 vs 84 and 74% (P=0.43, NS), while graft survival rates censored for patient death were 84 and 77 vs 82 and 77% for diabetic and non-diabetic subjects, respectively (P=0.52, NS). With graft survival results not censored for death with functioning graft, no significant change was seen (diabetic vs non-diabetic group: 77 and 54 vs 73 and 61%, P=0.19, NS). Age, but not the presence of diabetes, was the only factor significantly affecting patient survival when both patient groups were pooled. With regard to post-transplant complications requiring hospitalization, there was a significant difference only in the number of patients who had amputations (diabetic vs non-diabetic group: 8 vs 0, P=0.01). CONCLUSIONS: Patient and graft survival after kidney transplantation was similar in type 2 diabetic and matched non-diabetic subjects, with more amputations occurring in the diabetic group. Thus, at a single-centre level renal transplantation results almost equivalent to those in non-diabetic patients may be achieved in type 2 diabetes mellitus.     

2型糖尿病合并肾脏损害的病理与临床分析

目的 分析2型糖尿病患者出现肾脏病变时病理诊断与临床表现的关系.探讨肾活检在2型糖尿病伴有肾脏病变诊断的意义.方法 分析52例尿检异常和（或）Scr升高的2型糖尿病患者的临床特征和病理改变特点.结果 52例2型糖尿病患者经肾活检,32例确诊为糖尿病肾病（DN）,占61.5%,其中3例为糖尿病肾病合并非糖尿病性肾脏疾病（NDRD）;余20例为非糖尿病性肾脏疾病,占38.5%.肾活检前后诊断符合率46.15%,误诊率19.23%.两组间除BUN、Scr、糖尿病病程和是否伴有糖尿病性视网膜病变有显著差异外,其他临床表现和实验室检查的差异均无统计学意义.结论 2型糖尿病伴肾脏病变时相当部分是非糖尿病性肾脏病变,单纯依靠临床资料常难以鉴别,肾活检对明确糖尿病伴肾病变的性质具有重要的意义.     

Roux-en-Y胃旁路术对非肥胖2型糖尿病患者生活质量的影响

目的观察Roux-en-Y胃旁路术（RYGB）对非肥胖2型糖尿病患者生活质量的影响。方法2008年6月至2010年10月间,前瞻性入组37例非肥胖2型糖尿病患者接受RYGB治疗,分别于术前和术后12个月,通过简明健康状况量表（SF36）、糖尿病治疗满意度问卷（DTSQ）、2型糖尿病生活质量量表（DMQLS）评价患者的生活质量。结果37例患者术后血糖和血脂均显著下降（均P〈0．05）,糖尿病得到有效控制。术后12个月时,SF36生理相关综合评分（74．6±18．3）和精神相关综合评分（78．9±14．5）均高于术前（54．9±15．1和56．4±17．8,均P〈0．01）;DTSQ治疗满意度优于术前（29．2±7．1比15．4±5．6,P〈0．01）;DMQLS满意度亦优于术前（60．9±8．0比33．3±7．0,P〈0．01）。结论Roux-en-Y胃旁路术可有效地改善非肥胖2型糖尿病患者的生活质量。     

2型糖尿病肾脏损害病理类型分类初探

目的 探讨2型糖尿病肾脏损害病理类型的分类方法。 方法 回顾性分析49例除外非糖尿病肾病的伴显性白蛋白尿2型糖尿病患者的肾脏病理表现及临床特点,根据病理表现分为典型糖尿病肾小球病（DG）组和不典型糖尿病相关肾脏疾病（ADRD）组。 结果 DG占59.2%,ADRD占40.8%。病理表现上,DG的肾小球系膜区体密度、肾小球基底膜厚度、肾小管间质病变积分和肾小动脉玻璃样变发生率均大于ADRD,而足细胞相对密度低于ADRD。临床表现上,DG的糖尿病病程较长,糖尿病视网膜病变（DR）发生率高,空腹血糖较高,收缩压和平均动脉压较高,尿蛋白量较多,GFR下降更明显,而ADRD的体质量指数和肥胖比例较高,血脂紊乱更显著。DG和ADRD的GFR均与肾小球球性硬化率呈负相关,而DG的尿蛋白量水平与肾小球系膜区体密度呈正相关,ADRD的尿蛋白量水平与病理指标无显著相关。对DG诊断预测价值较高的有DR（阴性预测值94.8%）和已知糖尿病病程超过5年（阴性预测值90.7%)。 结论 2型糖尿病肾损害的病理表现多样,ADRD与DG是两种差异显著的2型糖尿病肾损害的病理表现,区分ADRD与DG能更好地从临床预测病理。     

Renal Replacement Therapy in Patients with Diabetic Nephropathy, 1980-1985: Report from the European Dialysis and Transplant Association Registry

Diabetic nephropathy, a rarely listed cause of end-stage renalfailure (ESRF) among patients starting renal replacement therapy(RRT) in the early seventies, has progressively gained in importanceand become one of the major reasons for the continuous growthof the patient population on RRT in most European countries.Amongst new patients commencing RRT in 1985, the acceptancerate varied between 3 and 12 per million population for typeI diabetes mellitus and between one and four per million populationfor type II diabetes mellitus. Nordic countries, particularlySweden and Finland, had the highest acceptance rate of youngpatients with type I diabetes mellitus whose median ages were38–42 years. In most central and southern European countriesthe median age of patients with type I diabetes mellitus variedbetween 50 and 58 years. The high number of young patients withtype I diabetes mellitus and ESRF in Nordic countries pointto a different natural history of this disease. It cannot beexcluded, however, that the higher median age in other countriesmight result from doctors mistakenly diagnosing type I diseasein patients with type II disease who need insulin treatment.Patients with type II diabetes mellitus had a similar age distributionat start of RRT throughout Europe and their median ages clusteredaround 60 years in most countries. The contribution of haemodialysis, peritoneal dialysis and renaltransplantation was analysed for diabetic compared to non-diabeticESRF. Despite large geographical differences in the proportionaluse of methods of treatment, a general trend to apply CAPD morefrequently in diabetic as compared to non-diabetic patientswas observed, and this was true for countries with both predominanthaemodialysis and predominant transplant programmes. Transplantationwithout prior dialysis was performed in 17% of Swedish and 30%of Norwegian patients with type I diabetes mellitus. In order to better explain the high mortality of patients withdiabetic ESRF, the proportional distribution of causes of deathwas analysed. Myocardial ischaemia and infarction was confirmedto be the leading cause of death in patients with diabetes mellituson RRT. The coronary death rate was estimated to be 10 timesgreater in young patients with type I diabetes mellitus as comparedto their non-diabetic counterparts. Other cardiovascular aswell as infectious causes were recorded in a similar proportionof deaths in diabetics as in non-diabetics. Cancer deaths, however,appeared to be definitely less frequent in patients on RRT dueto diabetic nephropathy.     

Treatment of diabetic nephropathy with angiotensin II receptor antagonist

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group (P = 0.02) and 23% lower than that in the amlodipine group (P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group (P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group (P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group (P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (−11% and −38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan. Received: October 18, 2002 / Accepted: December 17, 2002 Correspondence to:E.J. Lewis