Increased urinary albumin excretion aggregates with atherosclerotic risk factors in type 2 (non-insulin-dependent) diabetes mellitus

Supranormal urinary albumin excretion (microalbuminuria) is an early indicator of microangiopathy, i.e. diabetic nephropathy, and is associated with higher cardiovascular mortality in both type 1 and type 2 diabetes. The relationship between the presence of microalbuminuria and some atherosclerotic risk factors has been evaluated in 318 (170 male, 148 female) type 2 (non-insulin-dependent) diabetic subjects [age 63±10 years; known duration of diabetes 10.9±8.8 years; age at diabetes diagnosis 52±11 years; systolic blood pressure (BP) 150±23 mmHg; diastolic BP 86±11 mmHg (mean±SD)]. In early morning urine samples, albumin (immunonephelometry) and creatinine were assayed. On the basis of the albumin/creatinine ratio (A/C, mg/mmol), patients were categorized as normoalbuminuric (Na; A/C<2.0;n=159, 50%), microalbuminuric (ma; A/C 2–20;n=135, 42.5%) or macroalbuminuric (Ma; A/C >20;n=24, 7.5%). The three groups were closely matched for age, age at diagnosis, duration of diabetes, and fasting plasma and urinary glucose levels. Systolic and diastolic BP rose progressively with increasing urinary A/C ratio levels. While high-density lipoprotein (HDL) cholesterol was unaffected by albuminuria, total cholesterol (218±45 vs 198±43 mg/dl,P<0.001) and low-density lipoprotein (LDL) cholesterol (145±42 vs 131±38 mg/dl,P<0.05) levels were higher in microalbuminuric than in normoalbuminuric patients. Further, a significant correlation (r=0.16,P<0.01) existed between albuminuria and triglyceride concentrations. Prevalence of arterial hypertension, defined as BP160/95 mmHg and/or drug treatment (Na, 51%; ma, 65%; Ma, 78%;P<0.001) and obesity, defined as body mass index (BMI)>30 (Na, 15%; ma, 26%; Ma, 32%;P<0.05) rose with increasing A/C ratios. Both coronary heart disease (30% vs 15%) and intermittent claudication (18% vs 7%) were more frequent in microalbuminuric than in normoalbuminuric subjects. Finally, multiple stepwise regression analysis showed that urinary albumin excretion is significantly and independently associated with coronary heart disease and intermittent claudication, also taking into account hypertension and other established cardiovascular risk factors. In type 2 diabetes microalbuminuria tends to aggregate with risk factors for atherosclerotic vascular disease, e.g. increased prevalence of hypertension and obesity, elevated total and LDL cholesterol, and raised triglycerides levels. These abnormalities may only explain the excess of cardiovascular morbidity and mortality in part. Microalbuminuria per se may be an important and independent cardiovascular risk factor.     

Microalbuminuria in diabetes: a population study of the prevalence and an assessment of three screening tests

A single observer reviewed 842 of the 917 known diabetic patients registered with 40 GPs in the Poole area. A midstream urine specimen was tested for proteinuria using Albustix (Ames) and cultured to detect bacterial infection. After the first 3 months of the survey, the aliquot of this specimen was frozen for later determination of the random albumin/creatinine ratio (R-Alb/Creat). Patients were requested to submit a timed overnight urine collection for estimation of urinary albumin excretion rate (AER). Of the 842 patients reviewed, 493 (59%) submitted timed overnight urine collections; 43 were excluded because of urinary infection and/or proteinuria. One hundred and thirty-three (30%) of 450 diabetic patients were found to have microalbuminuria, although only 31 (7%) had an AER greater than 30 micrograms/min. Six hundred and seven urine samples were collected for R-Alb/Creat but 68 were excluded because of infection and/or proteinuria; in 10 further samples urinary creatinine was not measured. Two hundred and four (38%) of 532 diabetic patients were found to have an elevated R-Alb/Creat. There was a significant correlation between AER and R-Alb/Creat (r = 0.32, p less than 0.001) but a considerable number of patients showed either a normal AER and high R-Alb/Creat or the reverse. The value of R-Alb/Creat or an overnight urinary albumin concentration, or an overnight urinary albumin/creatinine ratio (ON-Alb/Creat) as screening tests to predict AER greater than 30 micrograms/min was assessed. An ON-Alb/Creat greater than 2.0 mg/mmol was the optimal screening test (sensitivity 96% and specificity 99.7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

糖尿病患者尿内皮素排量变化及其临床意义

目的　为研究尿内皮素（ Ｕ Ｅ Ｔ） 与糖尿病肾损害的可能关系和作用。方法　以放免法直接检测５２ 例正常人、３０ 例糖尿病、２８ 例早期糖尿病肾病和２５ 例糖尿病肾病患者 Ｕ Ｅ Ｔ 排量。结果各疾病组 Ｕ Ｅ Ｔ 排量显著高于正常人组（ Ｐ＜ ０ ．０１） 。糖尿病组尿白蛋白排泄率＜ ２０μｇ／ ｍｉｎ 时， Ｕ Ｅ Ｔ排量已显著增高。 Ｕ Ｅ Ｔ 与尿β２ 微球蛋白排量显著性正相关（ Ｐ＜ ０ ．０５） ，与血浆内皮素水平、内生肌酐清除率无相关。结论　糖尿病患者 Ｕ Ｅ Ｔ 水平随糖尿病肾病的严重程度而明显增高。 Ｕ Ｅ Ｔ 排量增高可作为糖尿病早期肾损害的敏感指标。     

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     

The relationship between autonomic neuropathy and urinary sodium and albumin excretion in insulin-treated diabetics

There is evidence to suggest that renal function may alter in the presence of autonomic neuropathy. Albumin excretion rate (AER) and sodium excretion rate (NaER) in timed daytime (erect) and night-time (supine) urine collections were assessed in 20 insulin-treated diabetics with and in 20 without established autonomic neuropathy, matched for age, sex, duration of diabetes, diabetic control, and systolic blood pressure. All patients were free of proteinuria on albustix testing and had normal serum levels of urea and creatinine. AER based on daytime and pooled 24-hour collections was higher, but not significantly so, in the group with autonomic neuropathy. The nocturnal AER on the other hand was significantly elevated in the group with autonomic neuropathy (p less than 0.02) as was the nocturnal urine volume (p less than 0.01) and sodium excretion rate (p less than 0.05). The corrected nocturnal albumin/creatinine ratio was likewise greater in this group (p less than 0.02). These findings suggest that autonomic neuropathy can independently affect renal function and that nocturnal renal haemodynamics and glomerulotubular balance may be deranged in insulin-treated diabetics with autonomic neuropathy.     

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.     

糖尿病前期尿白蛋白排泄率和微量白蛋白尿患病率的比较

目的　比较糖耐量正常 (NGT)、单纯空腹血糖受损 (I IFG)、单纯糖耐量低减 (I IGT)、糖耐量低减合并空腹血糖受损 (IGT/IFG)、新诊断的 2型糖尿病 (2型DM ) 5种不同糖代谢状态的尿白蛋白排泄率 (UAE)和微量白蛋白尿 (MAU )患病率。方法　根据 75g口服葡萄糖耐量试验 (75gOGTT)结果 ,将 2 93 4例受试者分为 :NGT组 13 3 2例、I IFG组 186例、I IGT组 470例、IGT/IFG组 2 3 6例、新诊断的 2型DM组 710例。用放射免疫法测定过夜 12h尿白蛋白。UAE在 2 0～ 2 0 0μg/min之间定义为MAU。 结果　 (1)UAE水平 [中位数 (四分位数 ) ] ,在新诊断的 2型DM组为8 50 (4 89～ 15 95) μg/min、IGT/IFG组为 6 93 (4 85～ 10 89) μg/min、I IGT组为 6 51(4 0 9～10 74) μg/min ,均高于I IFG组的 5 56(3 70～ 9 2 3 ) μg/min(P值均 <0 0 1) ;I IFG组与NGT组的 5 2 6(3 50～ 8 12 ) μg/min比较差异无显著性 (P >0 0 5) ;MAU的患病率在新诊断的 2型DM组为 2 0 7%、IGT/IFG组为 13 1%、I IGT组为 11 7%、I IFG组为 5 8%、NGT组为 5 6% ,同样呈现上述变化规律。(2 )多元逐步回归分析显示 :UAE与OGTT 2h血糖、舒张压、体重指数呈现独立正相关。logistic回归分析显示 ,导致MAU危险性增加的因素有OGTT 2h血糖、舒张     

Hydroxyproline Excretion is Increased in Diabetes Mellitus and Related to the Presence of Microalbuminuria

Increased fracture frequency and low bone mass have each been reported in patients with diabetes. To see if these were related to increased bone resorption we have measured the urinary excretion of hydroxyproline in 73 patients with Type 1 (insulin-dependent) diabetes, 67 patients with Type 2 (non-insulin-dependent) diabetes, and 75 control subjects. Hydroxyproline excretion was increased in both types of diabetes: Type 1: 21 (10–36) (median (IQR) μmol mmol creatinine^?1; Type 2: 25 (13–43) μmol mmol creatinine^?1; control: 10 (6–22) μmol mmol creatinine^?1 (p < 0.0001 and < 0.0002, respectively). Hydroxyproline excretion was not related to age, duration of diabetes or blood glucose control. Neither was it different in patients with or without retinopathy, neuropathy and macrovascular disease. However it was higher in patients with microalbuminuria at 35 (20–53) μmol mmol creatinine^?1 than in those with normal protein excretion (25(13–37) μmol mmol creatinine^?1 p = 0.03) or those with established proteinuria (18(8–26) μmol mmol creatinine^?1 p = 0.001). We conclude that there is evidence of increased bone resorption in diabetes and that this is related to alterations in renal function.     

血压对NIDDM患者尿白蛋白排泄的影响

本文对１６４例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者２４ｈ尿白蛋白排泄（２４ｈＵＡＥ）进行检测，结果显示：（１）在病程＜１０年的患者中，伴或不伴高血压者，２４ｈＵＡＥ无显著差异，但伴高血压者，微量白蛋白尿的发生率明显高于不伴高血压者，分别为３６．９％（１／１９）和７．９％（６／７６）；（２）在病程１０－２０年的患者中，伴高血压者，２４ｈＵＡＥ、微量及大量白蛋白尿的发生率均明显高于不伴高血压者；（３     

血和尿层粘连蛋白与2型糖尿病患者尿白蛋白关系的研究

目的　研究血、尿层粘连蛋白 (LN)与早期糖尿病肾病 (DN)的关系。方法　 2型糖尿病 (DM)患者 116例 ,分为正常蛋白尿组 (DMN组 ) 83例 ,微量蛋白尿组 (DMMA组 ) 3 3例 ;对照组 (C组 ) 3 1例。检测尿液LN、白蛋白(Alb)、肌酐 (Cr)和血清LN。结果　①尿LN/Cr在DMMA组高于C组 (P <0 0 5 ) ;血清LN在DMMA组高于C组及DMN组 (P <0 0 5 )。②DM患者尿Alb/Cr与尿LN/Cr(r =0 183 ,P <0 0 5 )、血清LN(r =0 3 5 7,P <0 0 1)均呈显著的正相关。③DM病程进入了血、尿LN和尿Alb/Cr的回归方程。结论　① 2型DM患者血、尿LN与尿Alb排出有一致性升高的趋势 ,血清LN是DM早期肾病标志蛋白。②整体DM组中DM病程为血、尿LN和Alb/Cr升高的危险因子。③本研究提示 2型DM患者中血、尿LN水平升高 ,并与DN的发生和严重程度有较好的相关性 ,尿、血LN水平可以用来监测DN的发生、病情进展和治疗效果     

Variability of albumin excretion in insulin-dependent diabetics

Sixteen adults patients with insulin-dependent diabetes mellitus and 16 healthy controls, matched for sex and age, were asked to collect their urine during the night and during the day at rest, at weekly intervals on four occasions. Subjects with heart failure, kidney disease, hypertension, abnormal urinalysis (Albustix positive) or poorly controlled diabetes prior to entry in the study, were excluded. A high variability in the albumin excretion rates (AER) was observed in both diabetic and control groups but the variance was significantly greater in diabetics. Moreover the variance in AER was higher in daytime as compared to overnight urine collections in both groups. Overnight urine collections are more precise than daytime urine collections for the determination of AER.     

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。     

糖尿病心率变异性分析与微量白蛋白尿的关系

目的 探讨糖尿病患者微白蛋白尿与心脏自主神经病变之间的关系。方法 应用２４小时动态心率变异性（ＨＲＶ）频率分析技术,对４６例糖尿病患者及３１例正常对照者测定了ＨＲＶ,并与尿白蛋白排泄率作相关分析。结果 糖尿病患者在不同尿白蛋白排泄（ＵＡＥ）阶段,心率变异性时域分析各项指标参数均为降低,其中伴微白蛋白尿组（ＤＭＢ）较正常蛋白尿组（ＤＭＡ）ＨＲＶ各项参数降低更明显,有极显著性差异（Ｐ〈０．０１）。糖尿     

Urinary Infection and Albumin Excretion in Insulin-dependent Diabetes Mellitus: Implications for the Measurement of Microalbuminuria

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3 %. Over the period of study, 20 of the patients (12 %) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen >10⁷ l⁻¹. Infection was more common in women than men (20 % vs 5 %, p<0.01) and was significantly associated with the presence of peripheral neuropathy (p<0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5 %) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.     

The variability of overnight urinary albumin excretion in insulin-dependent diabetic and normal subjects

The variability of overnight urinary albumin excretion rate (AER) and albumin to creatinine ratio was assessed in eight normal subjects and two groups of insulin-dependent diabetic patients divided on the basis of an initial overnight urinary albumin excretion rate below (n = 15) or above (n = 12) 30 micrograms/min. The latter group is known to be at risk of developing clinical diabetic nephropathy. An albumin to creatinine ratio of 2.6 and above identified all patients with an initial albumin excretion rate greater than 30 micrograms/min. The mean of the coefficients of variation, calculated from five successive overnight urine collections, for all subjects was 38% for albumin excretion rate and 37% for albumin to creatinine ratio. There was no significant difference in the variation of albumin excretion rate and albumin to creatinine ratio within or between the groups. Subsequent AERs from diabetics with an initial rate greater than 30 micrograms/min changed category more often (chi 2 = 11.9, p less than 0.001) than those from diabetics with lower initial rates and normal subjects. This was due to four subjects with initial values close to the cut-off level, whose subsequent values varied around it. Albumin excretion rates in normal subjects never exceeded 11 micrograms/min. Whether a patient's risk status is influenced by the degree of variation of albumin excretion rate around a risk level, or whether the classification of risk is improved by multiple collections, awaits testing in prospective subjects.     

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。     

A screening programme for microalbuminuria at a diabetes clinic in Apulia,southern Italy

Microalbuminuria is a predictor of renal and cardiovascular disease in both type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes. We report on a screening programme for microalbuminuria at a diabetes clinic in Italy. All diabetic patients without Albustix-positive proteinuria attending the clinic between April and September 1991 were screened. Microalbuminuria was defined as a urinary albumin/creatinine ratio, on an early morning sterile urine sample, >3 in at least two consecutive urine collections. Three hundred and fifty patients, 45 (20 female, 25 female) type 1 and 305 (145 male, 160 female) type 2 diabetics, were examined. The age range was 18–42 years and 36–73 years and duration of diabetes 1–24 and 1–35 years for type 1 and type 2 diabetic patients respectively. Blood pressure, lipids, glycosylated haemoglobin, body mass index and insulin dose, where appropriate, were measured in all patients. Microalbuminuria was found in 8 (22%) of the type 1 diabetics. These patients had a longer duration of diabetes (17.5 vs 7.4 years,P<0.001), higher diastolic blood pressure (86±2.1 vs 76±2.6 mmHg,P<0.05) and an increased total serum cholesterol level (203±23 vs 180±25 mg/dl,P<0.05) compared with diabetic patients with microalbuminuria. Of the type 2 diabetic patients 95 (33%) were found to have microalbuminuria and 210 (69%) nor-moalbumiuria. The prevalence of hypertension (defined blood pressure >140/90 mmHg or antihypertensive treatment) and of dyslipidaemia (defined as total cholesterol >200 and triglycerides >170 or hypolipidaemic treatment) were significantly higher (P<0.001 and 0.01 respectively) in patients with microalbuminuria. This study shows a prevalence of microalbuminuria in type 1 and type 2 diabetic patients similar to that reported in surveys of diabetes clinic outpatients in northern Europe. The association between microalbuminuria and recognized risk factors for cardiovascular and renal disease justifies screening programmes for microalbuminuria for early detection of at-risk diabetic patients and for the implementation of preventive therapeutic measures.     

不同储存温度和时间对糖尿病患者尿白蛋白测定的影响

研究了不同保存时间和温度对糖尿病患者尿白蛋白排出的率测定的影响。４１例糖尿病患者１２小时尿样本分别储存于室温、４℃、－２０℃的条件下，于当天、１４、３０、６０天测定尿白蛋白的含量。结果显示在４℃储存时，尿白蛋白浓度在６０天时无明显改变。室温下储存６０天时有轻度的降低。－２０℃储存一个月后有明显下降，９例（３９．１％）患者ＵＡＥ从２０－２００μｇ／ｍｉｎ降至正常范围，而４℃条件下只有３例（１３．１￥     

Microalbuminuria and urinary albumin excretion: French clinical practice guidelines

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans. IN DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria. MANAGEMENT: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.