Relationships between heart rate variability and urinary albumin excretion in patients with type 2 diabetes

BACKGROUND: Although in type 1 diabetes the close association between heart rate variability and urinary albumin excretion (UAE) is recognized even in patients with normoalbuminuria, this association has not yet been fully established in patients with type 2 diabetes. Therefore, we investigated the association in patients with type 2 diabetes. PATIENTS AND METHODS: All the hospital's 185 inpatients with type 2 diabetes were prospectively enrolled. Heart rate variability was evaluated by coefficients of variance of RR intervals (CVRR). RESULTS: The mean age, duration of diabetes, and hemoglobin A1C of the patients were 59.7+/-9.9 years, 10.4+/-7.8 years, and 9.7+/-2.3%, respectively. An analysis of the patients showed a significant negative correlation between CVRR and log10-transformed (log) UAE (R=-0.3340, P <0.0001). CVRR showed a significant negative correlation with age, duration of diabetes, hemoglobin AIC, systolic blood pressure, diastolic blood pressure, and triglyceride level. Log UAE showed a significant positive correlation with body mass index, hemoglobin A1C, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglyceride level. In the macroalbuminuric group (UAE above 300 mg/g creatinine; n=57), although CVRR showed a significant negative correlation with log UAE (R=-0.3571, P= 0.0064), but in normoalbuminuric (UAE below 30 mg/g Cr; n=79) and in microalbuminuric groups (30 to 300 mg/g Cr; n = 49), CVRR and log UAE showed no correlation. CONCLUSIONS: Our data suggest that in type 2 diabetes, the association between CVRR and UAE is significant only in patients with macroalbuminuria.     

老年糖尿病患者血清Apelin水平与尿白蛋白排泄率相关性分析

目的探讨老年糖尿病患者血清Apelin水平与尿白蛋白排泄率的相关性,为老年糖尿病肾病的预治提供临床依据。方法59例年龄在65岁以上的糖尿病患者和30例同年龄段健康对照者,采用酶联免疫吸附法测定空腹血清Apelin含量,同时检测空腹血糖及24小时尿白蛋白排泄率（UAER）,分析其相关性。结果59例糖尿病患者血清Apelin值为473±64．34,UAER为87．34±44．32,两者呈在非常显著的正相关（r=0．384,P〈0．01）。而对照组两指标无相关性。同时糖尿病组和对照组的血清Apelin水平与血糖值之间也无明显相关性。结论老年糖尿病患者血清apelin升高与UAER密切相关,提示血清Apelin水平可能是糖尿病肾病发生的因素之一。     

2型糖尿病患者肾小球滤过率与尿白蛋白的关系

目的探讨2型糖尿病患者慢性肾脏病(CKD)的患病率及肾小球滤过率与尿白蛋白排泄间的关系。方法收集自2008年1月至2009年12月在江苏省省级机关医院就诊的2型糖尿病患者资料,采用MDRD公式评估肾小球滤过率(eGFR),CKD定义为存在白蛋白尿或者eGFR60 ml/(min·1.73 m2)。白蛋白尿定义为尿白蛋白/肌酐比值(ACR)≥30 mg/g。采用多项式回归及曲线拟合分析eGFR与尿ACR之间的关系。结果研究纳入1521例2型糖尿病患者,平均年龄(63.9±12.0)岁,CKD及白蛋白尿的患病率分别为31.0%和28.9%。eGFR≥90、60~89、30~59、15~29 ml/(min·1.73 m2)患者白蛋白尿的患病率分别为19.9%、34.5%、65.6%和100%。在正常蛋白尿、微量白蛋白尿及大量白蛋白尿患者中,肾功能不全的比率分别为3.0%、9.3%和40.4%。多项式回归分析显示当患者尿ACR90 mg/g时,eGFR下降缓慢且稳定保持在90 ml/(min·1.73 m2)以上,而当尿ACR≥90 mg/g时,eGFR则迅速下降。结论 2型糖尿病患者CKD及白蛋白尿发生率高,对2型糖尿病人群进行CKD的筛查应该同时检测尿白蛋白与eGFR,为了延缓CKD的进展,应尽早对白蛋白尿进行干预治疗。     

血压正常的Ⅱ型糖尿病患者尿白蛋白排泄率与胰岛素抵抗的关系

目的 了解血压正常的Ⅱ型糖尿病患者尿白蛋白排泄率（ＵＡＥＲ）与胰岛素抵抗的关系。方法 对血压正常的３１例Ⅱ型糖尿闰中并微量白蛋白尿（ＭＡＵ）患者与３２例未合并ＭＡＵ患者的血糖，胰岛素、胰岛素敏感性指数（ＩＳＩ）进行比较分析，并对所有患者的ＵＡＥＲ与有关因素进行多因素逐步回归分析。结果 Ⅱ型糖尿病合并ＭＡＵ时ＩＳＩ显著降低，而且ＩＳＩ与ＵＡＥＲ呈独立的相关性「偏回归系数（β）＝－０．３９，Ｐ〈０．０     

2型糖尿病尿白蛋白排泄率与血栓调节蛋白的相关性研究

目的　探讨2型糖尿病(T2DM)患者尿白蛋白排泄率(UAER)与血栓调节蛋白(TM)的相关性。　方法　68 例T2DM患者分为正常白蛋白尿(NAU)组,微量白蛋白尿(MAU)组,临床白蛋白尿(CAU)组。30 例健康人作对照(NC)组。检测各组对象的血浆TM 水平、血小板计数(PC)、血小板平均容积(MPV)、血小板分布宽度(PDW)。　结果　MAU组和CAU组UAER显著高于NC组(P<0.01)。T2DM患者血浆TM含量均高于NC组(P<0.01)。UAER与TM水平呈正相关(r=0.798,P<0.05)。T2DM患者PC与NC组比较差异有统计学意义(P<0.01)。MPV、PDW在MAU组和CAU组显著高于NC组(P<0.01)。　结论　T2DM患者UAER与TM水平呈正相关。两者对糖尿病肾病的早期诊断及血管内皮细胞损伤程度的评价有重要意义。T2DM患者的PC、MPV和PDW高于NC组,且随着UAER的升高而增加。     

胰岛素样生长因子1与2型糖尿病尿白蛋白排泄率关系的临床研究

目的 探讨尿和血胰岛素样生长因子1(IGF-1)水平与2型糖尿病(T2DM)尿白蛋白排泄率的关系.方法 根据尿白蛋白排泄率(UAER)将80例T2DM患者分为正常白蛋白尿组(N-UAlb)32例,微量白蛋白尿组(M-UAlb)28例和大量白蛋白尿组(L-UAlb)20例.另设对照(NC)组20名.检测4组尿和血IGF-1水平.结果 (1)与NC组比较,T2DM三组血IGF-1明显降低,三组间血IGF-1水平无明显差异;(2)N-UAlb组尿IGF-1与NC组相比无明显差异;M-UAlb组和L-UAlb组尿IGF-1排泄较N-UAlb组显著增高;(3)尿IGF-1排泄与UAER和尿视黄醇结合蛋白排泄率呈正相关; 结论 2型糖尿病肾病尿IGF-1排泄的增加,提示可能有肾组织局部合成和分泌IGF-1的增加,后者可能是2型糖尿病肾病的发病机制之一.     

Serum uromodulin is associated with urinary albumin excretion in adolescents with type 1 diabetes

Early diabetic kidney disease (DKD) occurs in adolescents with type 1 diabetes (T1D). Lower serum uromodulin (SUMOD) predicts DKD progression in adults with T1D. In this study, we demonstrate that lower SUMOD is associated with urinary albumin excretion in adolescents with T1D, suggesting a potential relationship between SUMOD and early kidney dysfunction in T1D youth.     

Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes

The reason for the elevation of fibrinogen concentration in diabetic patients with nephropathy is not known so far. In order to elucidate the mechanism of such an increase in fibrinogen levels, we investigated haemorheological and inflammatory markers in type 2 diabetic patients in a cross-sectional design. Thirty-two non-smoking type 2 diabetic patients (13 women, 19 men; body mass index 29.1±5.4 kg/m², age 62.8±12.1 years) were investigated. Patietns with C-reactive protein levels > 1.5 mg/dl were excluded from the study. Concentration of fibrinogen was measured by immunonephelometry, C-reactive protein by immunoturbidimetry, and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay, and viscosity of plasma and of whole blood was determined by rotation viscosimetry. Concentrations of inflammatory parameters were well correlated with each other (p<0.05 for all correlations): IL-6 with C-reactive protein (r=0.48), and C-reactive protein with fibrinogen (r=0.41). While no associations were found with concentrations of C-reactive protein or IL-6, urinary albumin excretion was correlated with erythrocyte sedimentation rate (r=0.47) and with fibrinogen concentration (r=0.39; p<0.05). In patients with type 2 diabetes mellitus, urinary albumin excretion was not associated with concentrations of IL-6 or C-reactive protein. These results suggest an IL-6-independent mechanism for increased fibrinogen levels and erythrocyte sedimentation rate in type 2 diabetic patients with increased urinary albumin excretion. Received: February 2000 / Accepted in revised form: October 2001     

Rosiglitazone reduces urinary albumin excretion in type II diabetes

This study examines the effect of rosiglitazone on urinary albumin excretion (UAE) in patients with type II diabetes. Urinary albumin: creatinine ratio (ACR) was measured in a 52-week, open-label, cardiac safety study comparing rosiglitazone and glyburide. Patients were randomised to treatment with rosiglitazone 4 mg b.i.d. or glyburide. ACR was measured at baseline and after 28 and 52 weeks of treatment. Statistically significant reductions from baseline in ACR were observed in both treatment groups at week 28. By week 52, only the rosiglitazone group showed a significant reduction from baseline. Similar results were observed for the overall study population and for the subset of patients with baseline microalbuminuria. For patients with microalbuminuria at baseline, reductions in ACR did not correlate strongly with reductions in glycosylated haemoglobin, or fasting plasma glucose, but showed strong correlation with changes in mean 24-h systolic and diastolic blood pressure for rosiglitazone-treated patients (deltaACR vs deltamean 24-h systolic blood pressure, r=0.875; deltaACR vs deltamean 24-h diastolic blood pressure, r=0.755; P < 0.05 for both). No such correlation was observed for glyburide-treated patients. In conclusion, rosiglitazone treatment was associated with a decrease in urinary albumin excretion. These findings suggest a potential beneficial effect of rosiglitazone in the treatment or prevention of renal and vascular complications of type II diabetes.     

Genome-wide association studies in type 1 diabetes

Type 1 diabetes (T1D) is a chronic disease that typically manifests itself in childhood through the autoimmune destruction of pancreatic β cells, resulting in a lack of production of insulin. T1D is a multifactorial disease with a strong genetic component that is thought to interact with specific environmental triggers. Several genetic determinants of T1D were already established before the era of genome-wide association studies, primarily with the HLA class II genes, encoding highly polymorphic antigen-presenting proteins that account for almost 50% of the genetic risk for T1D. The recent development of high-throughput single nucleotide polymorphism genotyping array technologies has enabled investigators to perform high-density genomewide association studies in search of the remaining T1D loci. Combined with the well-established genes known for many years, 16 loci have now been uncovered to date as being robustly associated with the pathogenesis of this phenotype.     

西洛他唑对2型糖尿病尿白蛋白排泄率的影响

目的探讨西洛他唑治疗2型糖尿病早期肾病的临床疗效.方法将60例血压正常伴微量白蛋白尿的2型糖尿病患者,随机分为两组：治疗组30例,予口服西洛他唑片（50 mg,bid）;对照组30例,予口服安慰剂维生素B1（10 mg,bid）,两组均治疗3个月.观察患者治疗前后尿白蛋白排泄率（UAER）的变化.结果治疗组与治疗前比较,UAER明显下降（P＜0.01）,下降幅度达51.6%,约3%病人仅有轻微头痛反应.对照组治疗前后UAER无明显变化（均P＞0.05）.结论西洛他唑能显著降低糖尿病尿白蛋白的排泄,对糖尿病早期肾病具有治疗作用,且安全性好.     

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。     

Normal urinary albumin excretion in recently diagnosed type 1 diabetic patients

The urinary excretion of albumin and retinol binding protein were measured in 51 recently diagnosed Type 1 diabetic patients and 48 control subjects, matched for age and sex. The diabetic patients, admitted consecutively to the Steno Memorial Hospital, were all studied 3 to 6 months after the onset of diabetes. Urinary albumin excretion (median and 95% confidence interval) was similar in the diabetic patients and normal control subjects (8 (6-11) vs 8 (6-11) mg 24-h-1, NS). Four diabetic patients had urinary albumin excretion in the microalbuminuric range of 30-300 mg 24-h-1. There was no significant difference between the two groups in urinary excretion of retinol binding protein. The distribution among the individuals of both urinary proteins was positively skewed and similar in the two groups. In conclusion, no significant differences in the urinary excretion of albumin and retinol binding protein were found between recently diagnosed Type 1 diabetic patients and normal subjects.     

2型糖尿病患者尿蛋白排泄率与肌酐清除率关系分析

目的观察2型糖尿病患者尿白蛋白排泄率与肌酐清除率的关系。方法收集550例2型糖尿病患者的晨尿,测定即时尿标本白蛋白／肌酐比值（ACR）,同时测定血肌酐并计算肌酐清除率（Ccr）。结果在550例患者中Ccr〈60ml／min者106例,ACR增高者130例,约20％的患者ACR与Ccr不一致,且偏差较大,两者相关系数｜r｜为0．54,呈非高度相关。结论在筛查糖尿病肾病时既要测定尿白蛋白量,同时还应该计算肌酐清除率。     

2型糖尿病患者血中炎症因子、尿MCP-1与尿白蛋白排泄率的关系

观察84例不同尿白蛋白排泄率(UAE)的2型糖尿病患者血中炎症因子超敏C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)及红细胞沉降率(ESR)与尿单核细胞趋化蛋白1(MCP-1)水平的变化及临床意义.结果 发现2型糖尿病患者hs-CRP、TNF-α、尿MCP-1和ESR水平明显高于对照组,其中前三项指标随着UAE的增加而显著增加.提示糖尿病肾病与炎症反应相关.     

老年2型糖尿病患者尿蛋白排泄率与高敏C反应蛋白、血尿酸水平关系分析

目的探讨老年2型糖尿病(T2DM)患者尿蛋白排泄率(UAER)与高敏C反应蛋白(hs-CRP)、血尿酸(UA)水平的关系。方法根据UAER将94例老年T2DM患者分为3组,正常蛋白尿组(A组)、微量蛋白尿组(B组)和大量蛋白尿组(C组)。分别测定3组的hs-CRP、UA水平以及血压、血糖、血脂等相关临床生化指标,并进行比较。结果B组和C组hs-CRP、UA明显高于A组,B组和C组间也有统计学差异(P<0.05或P<0.01)。3组间在年龄、病程、血压、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、三酰甘油(TG)和高密度脂蛋白胆固醇(HDL-C)方面也存在显著性差异(P<0.05或P<0.01)。相关性分析显示,UAER与hs-CRP、UA均呈正相关(分别为r=0.331,P<0.01;r=0.254,P<0.05)。结论 hs-CRP和UA与老年糖尿病肾病(DN)的发生明显相关,在老年DN的预测中有一定临床意义。     

Long-term treatment with nifedipine reduces urinary albumin excretion and glomerular filtration rate in normotensive type 1 diabetic patients with microalbuminuria

The aim of the present study was to investigate the renal effects of long-term treatment with the calcium channel blocker nifedipine in normotensive type 1 diabetic patients with microalbuminuria. In a randomized, double-blind trial, 15 type 1 diabetic patients were treated with either nifedipine (n=8; dosage 30 mg/day) or placebo (n=7) for 12 months. At baseline and after 6 and 12 months of therapy, the albumin excretion rate (UAER, radioimmunoassay), glomerular filtration rate (GFR, chromium 51 ethylenediamine tetra-acetic acid clearance) and renal plasma flow (RPF, iodine 125 hippuran clearance) were determined. Nifedipine treatment caused a significant reduction of UAER after 6 and 12 months (median, Q₁/Q₃ in mg/24 h): baseline 84 (65/163); 6 months 35 (23/90),P<0.02; 12 months 39 (15/79),P<0.05. GFR was significantly decreased by nifedipine treatment (baseline 157±15, 6 months 122±8, 12 months 111±47 ml/min;P<0.05, mean ± SEM), whereas RPF remained constant. Nifedipine treatment did not influence systolic (baseline 121±7, 12 months 124±2 mmHg, mean ± SEM) or diastolic (baseline 72±2, 12 months 74±3 mmHg) arterial blood pressure. With placebo treatment no significant alterations of UAER, GFR, RPF and arterial blood pressure were observed. Metabolic control was constant throughout the whole study period. Thus, 1 year's treatment with nifedipine reduces the UAER and GFR in normotensive type 1 diabetic patients without influencing the systemic arterial blood pressure. The data, however, do not present a recommendation for the general use of nifedipine in these patients as the exact intrarenal mechanism of calcium channel blockers in humans remains to be established.     

Ambulatory pulse pressure and progression of urinary albumin excretion in older patients with type 2 diabetes mellitus

We studied whether ambulatory blood pressure monitoring added to office blood pressure in predicting progression of urine albumin excretion over 2 years of follow-up in a multiethnic cohort of older people with type-2 diabetes mellitus. Participants in the Informatics for Diabetes Education and Telemedicine study underwent a baseline evaluation that included office and 24-hour ambulatory blood pressure measurement and a spot urine measurement of albumin-to-creatinine ratio (ACR). Measurements of albumin-to-creatinine ratio were repeated 1 and 2 years later. In bivariate analyses, ambulatory 24-hour pulse pressure was the blood pressure variable most strongly associated with follow-up ACR. Repeated-measures mixed linear models (n = 1040) were built adjusting for baseline ACR ratio, clustered randomization, time to follow-up, and multiple covariates. When both were entered into the model, ambulatory 24-hour pulse pressure and office pulse pressure were independently associated with follow-up ACR (beta [SE] = 0.010 [0.002], P < 0.001, and 0.004 [0.001], P = 0.002, respectively). Cox proportional hazards models examined associations with progression of albuminuria in 954 participants without macroalbuminuria at baseline, adjusting for all of the covariates independently associated with follow-up ACR in mixed linear models. Ambulatory 24-hour pulse pressure, but not office pulse pressure, was independently associated with progression of albuminuria (P = 0.015 and 0.052, respectively). The adjusted hazards ratio (95% CI) per each 10-mm Hg increment in ambulatory pulse pressure was 1.23 (1.04 to 1.42). In conclusion, ambulatory pulse pressure may provide additional information to predict progression of albuminuria in elderly diabetic subjects above and beyond office blood pressure.