Longitudinal study of urinary albumin excretion in young diabetic patients--Wessex Diabetic Nephropathy Project.

AIMS: This study was established to follow changes in albumin/creatinine ratio (ACR) and to determine the prevalence and degree of progression of microalbuminuria (MA) or of clinical proteinuria (CP) in children with Type 1 diabetes. The study has investigated subjects for up to 12 years in establishing the correlation between MA and gender, age, duration of diabetes and glycated haemoglobin (HbA1c). The study has defined clinical cut-offs for MA in daytime clinic urine samples in young diabetic subjects. METHODS: Three hundred and sixty-one patients were involved in the study, with 221 (61.2%) having over six sets of data. Urine samples were collected at routine annual clinic visits and analysed without prior freezing for ACR. Blood samples were taken for HbA1c measurement. Data including sex, age and duration of diabetes were recorded. RESULTS: A random clinic ACR of < 4.5 mg/mmol (males) and 5.2 mg/mmol (females) creatinine was used as the 'clinical cut-off' to define the presence of MA. The presence of MA was independent of HbA1c and duration of diabetes but appeared be associated with the adolescent years (> 10 years). There was little evidence of progression from normoalbuminuria to MA, or from MA to CP. Of patients aged 10-18 years, 30.9% of males and 40.4% of females had one or more episodes of MA. CONCLUSIONS: Persistent MA and random episodes of MA or CP may be associated with the adolescent years but not with duration of diabetes. Further study will reveal if the substantial increases in ACR sometimes seen during adolescence are predictive of diabetic nephropathy. Clinical cut-offs of < 4.5 and < 5.2 mg/mmol creatinine for males and females, respectively, are suggested for the interpretation of changes in ACR in random urine samples in young people with Type 1 diabetes.     

Predisposition to nephropathy in Polynesians is associated with family history of renal disease, not diabetes mellitus.

AIMS: Familial clustering of diabetes and nephropathy suggests that either common environmental or inherited mechanisms are important in developing diabetic nephropathy. If an inherited mechanism is important, the albumin excretion rate might be increased in those at future risk. This study aimed to determine whether people with a family history of diabetes or people with a family history of renal disease were most at risk. METHODS: In a two-by-two factorial study of urinary albumin in non-diabetic Polynesians, 90 people with a first degree relative (FDR) with end-stage renal failure (ESRF) and diabetes (group 1) were compared with 90 people with a FDR with non-diabetic ESRF (group 2), with 90 people with a FDR with diabetes but no known nephropathy (group 3) and 90 people with no known relatives with either diabetes or nephropathy (group 4). Groups were matched for ethnicity and age. RESULTS: Subjects with a family history of ESRF (groups 1 and 2) had an increased mean albumin-creatinine ratio (1.25 vs. 1.00 mg/mmol, P = 0.01), but in subjects with a family history of diabetes (groups 1 and 3), the mean ratios were not significantly different from those without a family history of diabetes (1.06 vs. 1.17 mg/mmol; P = 0.2). In those with a family history of nephropathy, fasting blood glucose and systolic blood pressure were increased, while fasting insulin and 2 h insulin concentrations were lower. A family history of diabetes was associated with an increased fasting blood glucose and 2-h blood glucose. By multiple linear regression, the mean systolic blood pressure (P = 0.02), the 2-h glucose concentration (P = 0.05), a family history of renal failure (P = 0.04), female sex (P = 0.0001) and the total cholesterol (P = 0.01) were each independently associated with microalbuminuria, while a family history of diabetes was not (P = 0.09). CONCLUSIONS: These data suggest that among Polynesians there is no specific inherited tendency to diabetic nephropathy per se. The risk of nephropathy does not appear to be associated with the degree of familial risk of diabetes itself. Rather, the risk of diabetic nephropathy may be the result of a familial risk of nephropathy from any cause and is associated with diabetes through relative hypoinsulinaemia and hyperglycaemia.     

The impact of Type 2 diabetes and microalbuminuria on future cardiovascular events in patients with clinically manifest vascular disease from the Second Manifestations of ARTerial disease (SMART) study

Aims Type 2 diabetes mellitus and microalbuminuria are important risk factors for cardiovascular disease (CVD). Whether these two complications are important and independent risk factors for future CVD events in a high‐risk population with clinically manifest vascular disease is unknown. The objectives of this study were to examine the impact of Type 2 diabetes and microalbuminuria on future CVD events. Methods Patients with clinically manifest vascular disease (coronary, cerebral and peripheral vascular disease) from the Second Manifestation of Arterial disease study were followed up for 4 years. Data obtained from 1996–2006 were analysed. At baseline, there were 804 patients with Type 2 diabetes mellitus (mean age 60 years) and 2983 patients without. Incident CVD (n = 458) was defined as hospital‐verified myocardial infarction, stroke, vascular death and the composite of these vascular events. Results Both Type 2 diabetes [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.16, 1.75] and microalbuminuria (HR 1.86, 95% CI 1.49, 2.33) increased the risk of new cardiovascular events in univariate analyses. From multivariable models, presence of diabetes remained significantly and independently related to incident CVD (HR 1.42, 95% CI 1.11, 1.80). Presence of microalbuminuria also remained significantly independently related to incident CVD (HR 1.38, 95% CI 1.07, 1.77). In diabetes‐stratified analyses, the effect of microalbuminuria on CVD risk was observed only in patients with diabetes. In microalbuminuria‐stratified analyses, the significant and independent effect of diabetes on CVD risk was shown only in the non‐microalbuminuric group. Conclusions In this high‐risk population, both microalbuminuria and Type 2 diabetes are important and independent risk factors for future CVD.     

Kidney function and cardiovascular risk factors in non-insulin-dependent diabetics (NIDDM) with microalbuminuria

Microalbuminuria in non-insulin-dependent diabetes (NIDDM) is a strong predictor of increased mortality. The major causes of death are cardiovascular, whereas end-stage renal failure is of low frequency. To define kidney function and the presence of some assumed cardiovascular risk factors, we compared a group of 19 microalbuminuric NIDDM patients (M), of mean age (+/- SD) 65 +/- 4 years, and known duration of diabetes 8 +/- 7 years, with 19 randomly selected matched normoalbuminuric patients (N). Seven microalbuminuric patients (P) were also studied. Glomerular filtration rate (GFR) did not differ between N and M, whereas kidney volume was increased in M (260.3 +/- 54.1 ml 1.73 m-2) compared to N (220.4 +/- 44.8 ml 1.73 m-2; P = 0.018). The frequency of cardiac disease increased with increasing albuminuria. Glycaemic control did not differ between the groups, but fasting plasma C-peptide levels increased from 2.8 +/- 1.1 micrograms l-1 in N, to 3.7 +/- 1.7 micrograms l-1 in M (P = 0.08), and to 4.2 +/- 1.9 micrograms l-1 (P = 0.03) in P. The lipoprotein profile showed no significant differences, although the LDLcholesterol/HDLcholesterol (LDL-C/HDL-C) ratio tended to rise. A significant correlation was found between C-peptide and LDL-C/HDL-C (r = 0.5; P less than 10(-3]. In conclusion, GFR was not increased, and did not differ between N and M, whereas kidney volume was enhanced in M. Several assumed cardiovascular risk factors showed values of M intermediate between those of N and P.     

联合检测血同型半胱氨酸、糖化血红蛋白与尿微量白蛋白、β_2-微球蛋白在2型糖尿病早期肾损害诊断的临床价值

目的探讨血同型半胱氨酸(Hcy)、糖化血红蛋白(HbA1c)、尿微量白蛋白(尿mALB)、尿β2-微球蛋白(尿β2-MG)等指标对2型糖尿病(T2DM)早期肾损害的诊断价值。方法回顾性分析我院196例不同病程2型糖尿病患者及同期158例健康体检人员的HbA1c、血Hcy、尿mALB、尿β2-MG检测结果,并进行统计学处理。结果在T2DM患者中Hcy阳性率(男:47.6%,女:50.5%)最高,且存在性别差异;尿β2-MG阳性率(男:25.2%,女:24.7%)最低;这四项指标中,糖尿病组均明显高于对照组,且随着病程的延长,这些指标较糖尿病初期增高明显。结论定期联合检查T2DM患者HbA1c、血Hcy、尿mALB、尿β2-MG能及时了解糖尿病早期是否存在肾损害及其部位(肾小球、近端肾小管),以便临床医生及时采取有效措施,防止或延缓糖尿病肾病的发生。     

一种快速检测尿中微量白蛋白的高效液相色谱法

目的:建立一种快速检测尿中微量白蛋白的高效液相色谱检测方法。方法:采用新的流动相建立分子筛-高效液相色谱法测定人血清白蛋白标准液和尿液白蛋白, 对该法进行方法学性能研究并分析56 例糖尿病患者的尿液标本。结果:色谱柱Agilent Zorbax GF-250 以0.1% 甲酸水溶液与乙腈(85:15) 为流动相, 流速1 mL/min, 检测波长205nm 时, 人血清白蛋白标准液和尿液白蛋白均在1.7 min 出峰。在5~2000 mg/L 范围内线性关系良好(r²=0.9969);检测低限为2 mg/L;批内和批间变异系数分别为3.98% 和4.05% (20 mg/L)、3.55% 和3.60%(200 mg/L) 及4.65% 和4.74% (2000mg/L);回收率分别为95.3%, 98.1% 和97.2%。56 例糖尿病患者标本, 高效液相色谱法能检出30 例微量白蛋白尿, 免疫散射比浊法检出15 例, 高效液相色谱法的检出率明显高于免疫散射比浊法(P<0.05)。结论:采用甲酸水溶液与乙腈为流动相的分子筛- 高效液相色谱法能较其他方法检出更多的微量白蛋白, 且快速, 灵敏度高, 适合临床常规测定。     

厄贝沙坦与氨氯地平对高血压病患者尿微量白蛋白的影响

目的评价厄贝沙坦与氨氯地平在有效降压的同时,对尿微量白蛋白的影响.方法选择129例高血压病合并早期肾损害微量白蛋白尿高的患者,随机分为三组:第一组(ARB组)43例给予厄贝沙坦治疗;第二组(CCB组)43例给予氨氯地平治疗;第三组(对照组)43例给予倍他乐克或/和双氢克尿噻治疗;血压达标12个月后,观察及比较各组治疗前、本组治疗前后以及各组治疗后的尿微量白蛋白变化.结果各组治疗前,性别、年龄、体重指数、收缩压/舒张压、病程等比较无差异(P>0.05).尿微量白蛋白数值比较:各组治疗前无差异(P>0.05);治疗12月后,ARB组和CCB组治疗后均低于治疗前(P<0.05),对照组高于治疗前(P<0.05);ARB组低于CCB组,CCB组低于对照组(P<0.05).结论厄贝沙坦与氨氯地平在有效降压的同时,均可降低尿微量白蛋白水平,起到有效地保护肾功能的作用,尤其是厄贝沙坦保护作用优于氨氯地平.     

尿微量白蛋白与早期肾损害的关系

目的:探讨尿微量白蛋白(Microalbuminuria,MA)与早期肾损害关系,以便发现早期肾损害,提前进行预防和治疗。方法:用免疫比浊法,对我院住院的内分泌科糖尿病患者和心内科高血压患者与健康对照人群的尿微量白蛋白(MA)进行对比分析。结果:糖尿病和高血压患者的尿微量白蛋白(MA)检测阳性率明显高于健康对照人群,差异有显著性(P<0.05),且与病程及年龄有关,而与性别无关。结论:尿微量白蛋白(MA)可作为早期肾损害的重要指标之一。