Assay of microalbuminuria using gel electroimmunoassay

The possibility of using electroimmunoassay as a technique for assessing microalbuminuria in the diabetic population has been studied. The method was found to be precise (given inter-batch coefficients of variation of 5.7% and 5.8% at levels of 16 mg/l and 23 mg/l respectively), showed adequate sensitivity, and produced results which correlated well (r = 0.971) with these obtained from a routine radioimmunoassay procedure. It is concluded that electroimmunoassay provides a reliable alternative to more sophisticated techniques in the non-specialized laboratory dealing with only moderate numbers of specimens.     

C-reactive protein and microalbuminuria are associated with atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk for cardiovascular disease. It is important to detect AF at an early stage and to search for new pathophysiological pathways to intervene. We hypothesized that microalbuminuria and C-reactive protein (CRP), a marker of generalized vascular damage and inflammation, respectively, are associated with AF. METHODS: Standard 12-lead electrocardiograms were recorded in 7546 subjects (mean age 49+/-13 years, 51% male). AF was defined according to Minnesota codes. The urinary albumin excretion rate was measured as the mean of two 24-h urine collections and microalbuminuria was defined as an albumin excretion rate between 30 and 300 mg per 24 h. High-sensitive CRP was dichotomized (low: three lowest quartiles, CRP<2.87 mg/l vs. high: highest quartile, CRP>2.87 mg/l). Data are expressed as odds ratios (95% confidence intervals). RESULTS: AF was present in 75 (1.0%) subjects. In multivariate analysis, an age >60 years, the presence of ischemic heart disease, left ventricular hypertrophy, elevated CRP level (1.79 [1.07-2.97], p=0.03) and microalbuminuria (1.93 [1.10-3.37], p=0.02) were significantly associated with AF. Surprisingly, the combination of elevated CRP and the presence of microalbuminuria showed an even higher association with AF after adjusting for all cardiovascular risk factors (3.80 [1.89-7.63], p<0.001). CONCLUSIONS: An elevated CRP level and microalbuminuria are associated with AF. Moreover, the combination of both indicates a fourfold higher association with the presence of AF in a population at large.     

Effects of strict blood pressure control by a long-acting calcium channel blocker on brain natriuretic peptide and urinary albumin excretion rate in Japanese hypertensive patients

Strong adherence to antihypertensive therapy has been shown to reduce the frequency of cardiovascular events by strictly controlling blood pressure. Although calcium channel blockers (CCBs) are among the most popular antihypertensive drugs in Japan, few trials have been conducted using high CCB doses in Japanese patients. In this study, we administered amlodipine 5 mg or 10 mg to patients with hypertension in order to compare the efficacy and tolerability of low and high doses, and measured two surrogate markers of hypertensive target organ damage, i.e., brain natriuretic peptide (BNP) as a risk marker of cardiac overload and microalbuminuria as a measure of renal damage. Seventy-two patients were randomly assigned to either amlodipine 5 mg (n = 35) or 10 mg (n = 37) dose groups. The latter group achieved greater reductions in clinic as well as both morning and evening home BP levels without an increase in pulse rate (the differences between the two groups in clinic/morning/evening systolic BP were 4.7/4.7/5.4 mmHg, and for diastolic BP they were 4.2/3.6/3.8 mmHg). Reductions in BNP and urinary albumin/creatinine ratio (UAR) levels were significantly correlated with the reductions in systolic BP levels (BNP, clinic/morning BP: r = 0.256, p = 0.030/r = 0.330, p = 0.005; UAR, clinic BP: r = 0.316, p = 0.007). In conclusion, the higher dose (10 mg) of amlodipine induced greater reductions in all BP levels than did the lower dose, without increasing the pulse rate. These additional reductions were significantly correlated with reductions in hypertensive cardiac overload, as evaluated by BNP levels, and a reduction in renal damage, as evaluated by microalbuminuria levels. Moreover, a reduction in the microalbuminuria may have occurred concomitant with a reduction in clinic systolic BP level.     

Diagnostic significance of transferrinuria and albumin-specific dipstick testing in primary care patients with elevated office blood pressure

This study assesses the diagnostic accuracy of transferrinuria and an albumin-specific dipstick assay for detection of renal target organ damage (microalbuminuria) in hypertensive patients in a general practice setting. A spot urine sample of 130 nondiabetic patients with elevated office blood pressure readings (>140 and/or 90 mmHg) was investigated by measuring albumin to creatinine ratio (ACR) and transferrin to creatinine ratio (TCR) and by using an albumin-specific dipstick test (Micral). ACR was considered as comparative gold standard. TCR was elevated (>0.19 mg/mmol) in 26 urine samples (20.0% of the test samples). ACR was raised in 29 samples (22.3% of the test samples). Elevated TCR had a sensitivity of 97% and specificity of 91% for detection of microalbuminuria. Positive predicting value for microalbuminuria was 65%; negative predicting value was 99%. Correlation between ACR and TCR was strong (r=0.96). Dipstick testing for albumin was positive in 23 urine samples (17.7% of the test samples), 27 (20.8%) tests were false positive and six (4.6%) false negative. When dipstick was positive, the sensitivity of detecting microalbuminuria was 79%, and specificity 73%. In conclusion, detection of urinary transferrin in nondiabetic patients with hypertension is strongly associated with urinary albumin excretion. However, assessment of TCR does not identify additional patients with microalbuminuria compared to measurement of ACR alone. The semiquantitative Micral test offers a simple and valuable method to screen hypertensive patients for microalbuminuria in a primary care setting.     

糖尿病肾病肾小球滤过膜结构与肾功能及代谢指标的关系

目的:观察2型糖尿病肾病(T2DN)患者肾小球滤过膜超微结构改变与肾功能及代谢指标的关系.方法:将明确诊断的T2DN 75例患者分为:微量白蛋白尿组(尿白蛋白/24h 30～300 mg);蛋白尿组(尿蛋白0.5～2.0g/24h)和大量蛋白尿组(尿蛋白＞3.5g/24h).收集三组患者临床指标,并分别使用Cockcroft-Gault公式、简化的肾脏疾病饮食控制(MDRD)公式等计算患者的肾小球滤过率(eGFR);采用形态学计量分析方法分别测算肾小球体积、肾小球足细胞和内皮细胞的相对密度、绝对数目和足细胞足突宽度及肾小球基膜(GBM)厚度.结果:(1)肾小球滤过膜结构与GFR的关系:微量白蛋白尿组Ccr与肾小球足细胞密度及数日均负相关(分别为r=-0.480,P＜=0.05;r=-0.478,P＜0.05);大量蛋白尿组以SCr估算的eGFR与肾小球足细胞密度正相关(r=0.462,P＜0.05);余均未见明显相关.(2)多元回归分析结果:微量白蛋白尿组中肾小球足细胞密度、糖化血红蛋白、三酰甘油、尿酸与Ccr相关(R~2=0.616,P＜0.01);大量蛋白尿组肾小球足细胞密度、尿酸与以SCr估算的eGFR相关(R~2=0.613,P＜0.01).(3)肾小球滤过膜结构及肾小球体积与糖、脂质代谢指标的关系:①肾小球体积与血糖的关系:微量白蛋白尿组中肾小球体积和糖化血红蛋白正相关(r=0.425,P＜0.05);而在蛋白尿组则为负相关(r=-0.427,P＜0.05).②GBM厚度与血糖、血脂代谢指标的关系:微量白蛋白尿组中,以GBM厚度为因变量,糖及脂质代谢水平为自变量,可见空腹血糖水平和总胆固醇与基膜厚度相关(R~2=0.247,P＜0.05).结论:肾小球滤过膜结构与GFR及糖、脂质代谢水平间存在着密切联系,且与DN发展的不同阶段相关.     

Evaluation of the HemoCue plasma haemoglobin analyser for assessing haemolysis in red cell concentrates during storage

BACKGROUND AND OBJECTIVES: To evaluate the HemoCue plasma haemoglobin (Hb) analyser for determining supernatant Hb in red cell concentrates (RCC) during storage and compare this to a spectrophotometric method. MATERIALS AND METHODS: Samples from RCC (n = 20) at days 0, 7, 21, 35 and 42 of storage were tested by both methods for supernatant Hb. RESULTS: Results are given as median with range. There was a significant correlation (r = 0.97, P < 0.0001), but statistically significant difference between the two methods (0.72 (0.36-2.77) spectrophotometric vs. 0.70 (0.3-2.6) g/l HemoCue). However, the mean bias was negligible at 0.06 g/l. The HemoCue method gave a interassay coefficient of variation of 5.6% at 1.2 g/l and was linear to at least 20 g/l. CONCLUSION: The HemoCue plasma haemoglobin analyser is a simple, rapid, reliable and accurate method for the determination of supernatant Hb in RCC at the end of storage and compares well to established methods for supernatant Hb measurement.     

Microabluminuria in arterial hypertension. Measurement, variables, interpretation, recommendations

Permanent hypertension is frequently associated with increased glomerular permeability to albumin at an early stage, indicating renal involvement and endothelial dysfunction. The definition of microalbuminuria is an urinary albumin excretion of 30-300 mg/24 hrs, confirmed on two occasions over a 3 month period. It may also be expressed in microgram/min, m/l or mg/mmol of creatinine. Radio-immunological, immunonephelometric methods and Elisa are specific and the most sensitive methods of measurement. There is a large intra-individual variability (25-60%) making it essential to repeat measurements always by the same technique. The prevalence of microalbuminuria is 5-8% in the general population and 6-24% in hypertensive patients. When present, it is a marker of increased cardiovascular risk. Clinical recommendations suggest adaptation of urinary collection according to the context: screening, diagnosis or clinical research. It is always necessary to start by dip-stick detection of proteinuria, haematuria or urinary infection. Clinical research requires repeated measurement of 24 hour microalbuminuria, sometimes divided into two periods of day and night, often associated with ambulatory blood pressure recordings and renal function tests. Studies of the effects of anti-hypertensive drugs on microalbuminuria could provide better evaluation. In conclusion, measurement of microalbuminuria remains a tool of clinical research allowing an assessment of cardiovascular and renal risk of hypertensive patients.     

A simple method for assessing intestinal inflammation in Crohn's disease

BACKGROUND AND AIMS: Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome. METHODS: The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn's disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of (111)indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn's disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic. RESULTS: Four day faecal excretion of (111)indium (median 8.7%; 95% confidence interval (CI) 7-17%; normal <1.0%) correlated significantly (p<0.0001) with daily (median ranged from 39 to 47 mg; normal <3 mg; r=0.76-0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45-168 mg; normal <11 mg; r=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36-175 mg/l; normal <10 mg/l; r=0.70) in patients with Crohn's disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2-3 mg/l) and those with Crohn's disease (91 mg/l; 95% CI 59-105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn's disease and irritable bowel syndrome. CONCLUSION: The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn's disease and irritable bowel syndrome.     

Altered exercise gas exchange as related to microalbuminuria in type 2 diabetic patients

STUDY OBJECTIVE: Microalbuminuria in diabetes mellitus is a risk factor for cardiovascular disease. We hypothesized that microalbuminuria in type 2 diabetic patients is related to impaired cardiopulmonary function during exercise, and that the severity of impairment is correlated with the degree of microalbuminuria. DESIGN: Twenty of each of the following categories of subjects performed symptom-limited cardiopulmonary exercise testing on a cycle ergometer: (1) type 2 diabetic patients with normoalbuminuria (daily urinary albumin excretion [UAE] < 30 mg/d); (2) type 2 diabetic patients with microalbuminuria (daily UAE, 30 to 300 mg/d); and (3) normal control subjects. MEASUREMENTS AND RESULTS: Oxygen consumption (VO(2)) of patients with microalbuminuria was lower than that of control subjects at anaerobic threshold (AT) [p < 0.001], and was lower than both control subjects (p < 0.001) and patients with normoalbuminuria (p = 0.015) at peak exercise. There was a progressive worsening in gas exchange efficiency at the lungs, as measured by minute ventilation (VE)/carbon dioxide production (VCO(2)) at AT or DeltaVE/DeltaVCO(2) slope, (p = 0.006 and p = 0.019, respectively) going from control subjects to patients with normoalbuminuria and then to patients with microalbuminuria. Left ventricular ejection fractions and BP were similar in patients with normoalbuminuria and microalbuminuria. More patients with microalbuminuria (n = 9) than with normoalbuminuria (n = 2) demonstrated diastolic dysfunction (p = 0.013). These 11 patients had lower peak VO(2) values (p = 0.001) and higher daily UAE (p = 0.028). An inverse linear relationship was found between peak VO(2) and log(10) daily UAE (r = - 0.57, r(2) = 0.29, p < 0.001). CONCLUSIONS: Abnormalities reflecting reduced oxygen transport and impaired gas exchange efficiency were found during exercise, and were especially profound in patients with microalbuminuria. These changes could be secondary to pulmonary microangiopathy and myocardial interstitial changes. Increases in capillary permeability to proteins may take place in the myocardium as they do in the kidneys, and contribute to impaired myocardial distensibility and hence diastolic dysfunction.     

Fibronectin concentrations in the plasma of newborn infants and their mothers and various plasma preparations

The article describes a method for the quantification of plasma fibronectin (FN) by means of electroimmunodiffusion after Laurell. By this means the fibronectin concentrations of healthy, mature newborns as well as of their mothers were determined. The average FN-level of the newborns lies at 33% related to the value for adults and at 48%, respectively, related to the maternal FN-content. There is no difference between male and female newborns. The FN-concentrations of the adults stated by us with 330 and 314 mg/l, respectively, for males and females correspond to the data in literature. Furthermore, the FN-content in plasma preparations was determined, with an average value of 2,356 mg/l this was highest in the factor-VIII-concentrate. The expediency and the prerequisites for a possible fibronectin substitution are discussed.     

Low-density lipoprotein cholesterol estimation by a new formula in Indian population

BACKGROUND: Estimation of low-density lipoprotein cholesterol is crucial in the management of ischemic heart disease patients. Low-density lipoprotein cholesterol is routinely calculated in laboratories world over by applying Friedewald formula for logistic reasons. We derived a new formula based on multiple regression approach. METHODS: Lipid profiles were done on blood samples of 2008 patients. In initial 1000 patients, low-density lipoprotein cholesterol was estimated by a direct method and also by Friedewald formula. By applying linear regression methods on the data of direct estimation method, a new formula was obtained and the accuracy of this new formula was validated in the next 1008 patients. RESULTS: The mean low-density lipoprotein cholesterol was 116+/-41.5 mg/dl (3.02+/-1.08 mmol/l) measured by direct low-density lipoprotein cholesterol assay and that calculated by Friedewald formula was 119+/-46 mg/dl (3.09+/-1.2 mmol/l) for the initial 1000 patients. Low-density lipoprotein cholesterol measured by direct low-density lipoprotein cholesterol assay and calculated from Friedewald formula showed good correlation (r = 0.88), however, there was minimal overestimation by the Friedewald formula. The correlation improved between direct low-density lipoprotein cholesterol and calculated low-density lipoprotein cholesterol after excluding the patients with triglycerides more than 350 mg/dl (r = 0.92). The mean low-density lipoprotein cholesterol measured by the direct assay and by new formula in the next 1008 patients was 117+/-40 mg/dl (3.04+/-1.04 mmol/l) and 113.7+/-37 mg/dl (2.96+/-0.96 mmol/l), respectively with very good correlation (r = 0.97) between them. CONCLUSIONS: The new formula derived from multiple linear regression analysis appears to be more accurate than Friedewald formula in Indian population.     

Screening for Microalbuminuria: Which Measurement?

It now seems worth while to identify Type 1 diabetic patients with microalbuminuria, as improved blood glucose control and reduction of arterial blood pressure will slow if not prevent the progression to persistent proteinuria. Measurement of albumin excretion rate (AER) in a timed urine sample remains the gold standard for the definition of microalbuminuria, but is not a practical screening procedure. Thus attempts have been made to relate the albumin concentration of albumin:creatinine ratio in random or first morning urine samples to AER. There is a weak correlation of albumin concentration (r = 0.32 to 0.68) and albumin:creatinine ratio (r = 0.43 to 0.54) in a random urine sample with AER, and low sensitivity and specificity of a variety of different albumin concentrations and albumin:creatinine ratios to predict microalbuminuria. The correlation of albumin concentration (r = 0.86 to 0.90) and albumin:creatinine ratio (r = 0.74 to 0.91) in an early morning urine sample with AER is stronger. Measurement of albumin:creatinine ratio in an early morning urine sample appears to be the most reliable method of screening for microalbuminuria, with sensitivity of 88 to 100% and specificity 81 to 100% depending on the cut-off ratio chosen and the definition of microalbuminuria used. If the albumin:creatinine ratio in an early morning urine sample is less than or equal to 3.5 mg mmol-1, the patient can be classed as normoalbuminuric and re-screened annually. If the ratio is greater than or equal to 10.0 mg mmol-1, confirmation of microalbuminuria should be sought in a timed urine collection and appropriate therapy begun.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microalbuminuria in insulin sensitivity in patients with growth hormone-secreting pituitary tumor

CONTEXT: Impaired glucose tolerance and diabetes mellitus are frequently present in acromegalic patients in whom the degree of impaired glucose metabolism seems directly correlated with GH levels. Microalbuminuria is reported to be directly correlated with insulin resistance, and both conditions predict cardiovascular disease mortality. OBJECTIVE: Our objective was to investigate the microalbuminuria levels as a marker of endothelial dysfunction in acromegalic patients. DESIGN: We conducted an observational, multicenter, open prospective study. SUBJECTS: Subjects included 74 patients with active acromegaly (52 with normal glucose tolerance, 16 with impaired glucose tolerance, and six with diabetes), and 50 healthy subjects matched for age, gender, and body mass index were studied as controls. RESULTS: In the whole group, mean GH and IGF-I levels were 24.2+/-3.9 ng/ml and 700.1+/-23.0 microg/liter, respectively. The insulin sensitivity index (ISI) in the patients was lower than in the controls (P<0.0005). In impaired glucose tolerance and diabetic patients, microalbuminuria was higher than in normal glucose tolerance patients (P<0.05 and P<0.0005 respectively). Hypertensive patients had higher levels of microalbuminuria than normotensive ones (P<0.005). The levels of microalbuminuria related to creatinine were directly correlated with fasting glucose levels (r=0.27; P=0.0019), fasting insulin levels (r=0.28; P=0.017), and insulin after 90 (r=0.26; P=0.027) and 120 min after glucose load (r=0.26; P=0.023) and indirectly correlated with ISI composite (P<0.0001; r=-0.48). By a multivariate analysis, the log-ISI composite was the strongest predictor of microalbuminuria (t=-3.19; P=0.0021). CONCLUSIONS: Impairment of glucose tolerance in acromegaly is associated with high levels of microalbuminuria. For this reason, microalbuminuria should be part of cardiovascular risk assessment in these patients.     

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

AIMS/HYPOTHESIS: We determined the longitudinal relationship between adiponectin levels and the development of microalbuminuria in an inception cohort of children with type 1 diabetes. METHODS: Blood samples collected annually over a median of 9.0 (range 1.3-14.9) years were assayed for adiponectin and HbA(1c) in 55 children (36 girls) with type 1 diabetes and microalbuminuria whose age of onset of diabetes was 9.4 years (range 2.2-15.4). Samples were also assayed from normoalbuminuric children (controls) matched for age, sex and duration of diabetes. RESULTS: Overall, adiponectin levels were higher in girls than in boys, but only after 11 years of age (median [range]: 15.3 [5.8-124.4] vs 11.6 [4.1-26.5] mg/l, p < 0.001). Furthermore, adiponectin levels were higher in girls with microalbuminuria than in control girls, but this was only apparent after the onset of microalbuminuria (p = 0.001, adjusted for BMI, daily insulin dose, HbA(1c) and age). In boys, adiponectin levels did not differ between those with microalbuminuria and controls. Further sex-related discordant associations with adiponectin levels were observed; in girls, adiponectin levels were positively related to HbA(1c) levels (r = 0.2, p = 0.05) and urine albumin excretion (r = 0.3, p < 0.05) and inversely related to BMI (r = -0.2, p < 0.05). These associations were absent in boys. CONCLUSIONS/INTERPRETATION: In adolescent girls with type 1 diabetes but not in boys, adiponectin levels increase with increasing urine albumin excretion and onset of microalbuminuria. Although causal links cannot be inferred, this sexual dimorphism may reflect interactive effects of hyperglycaemia and sex steroids on risk of complications and adiponectin production.     

The IGF-I system and the renal and haemodynamic effects of losartan in normotensive patients with type 2 diabetes mellitus: a randomized clinical trial

OBJECTIVE: Losartan has been shown to protect the diabetic kidney, at least partly independent of changes in blood pressure. Imbalances in the IGF-I system are associated with the development of diabetic nephropathy. We investigated whether renal as well as haemodynamic effects of losartan are associated with changes in the IGF-I system in normotensive patients with type 2 diabetes mellitus (T2DM). DESIGN AND PATIENTS: This randomized, double-blind placebo-controlled clinical trial involved 74 normotensive patients with T2DM and microalbuminuria. Thirty-eight patients were assigned to receive losartan and 36 patients were assigned to receive placebo for 10 weeks. MEASUREMENTS: Serum levels of total and free IGF-I, IGFBP-3, creatinine and haemoglobin A(1c) (HbA(1c)), as well as urinary albumin excretion rate, creatinine clearance and blood pressure, were measured prior to the start of treatment and after 10 weeks of treatment. RESULTS: At baseline, serum levels of IGFBP-3 were elevated and serum levels of free IGF-I were reduced. Losartan tended to reduce IGFBP-3 levels and to increase free IGF-I levels, although neither effect was statistically significant. These effects were more pronounced in a subanalysis of 18 losartan-treated patients with stable metabolic parameters, with a decrease in IGFBP-3 from 133.2 to 122.6 nmol/l (P=0.006) and an increase in free IGF-I levels by 8% (ns). Serum levels of total IGF-I were unaffected. The change in IGFBP-3 was inversely correlated to the change in creatinine clearance (r=-0.4; P=0.02). Total and free IGF-I inversely correlated to systolic blood pressure (r= -0.46; P=0.007 and r=0.26; P=0.14 respectively). Furthermore, changes in total IGF-I and IGFBP-3 correlated to changes in serum creatinine levels in the metabolically stable patients (r=0.58, P=0.02 and r=0.6, P=0.01, respectively). Changes in the IGF-I system were unrelated to a reduction in microalbuminuria associated with losartan. CONCLUSIONS: Losartan lowered the elevated levels of IGFBP-3, although only significantly in the metabolically stable patients. A tendency towards an increase in free IGF-I levels was also observed, but this change was small and not statistically significant. These changes were not related to reduction in microalbuminuria, but might contribute to effects of losartan on creatinine clearance and blood pressure of losartan in normotensive patients with T2DM.     

尿脂联素与糖尿病肾病严重程度的相关性研究

目的 探讨尿脂联素与糖尿病肾病严重程度的相关性.方法 150例糖尿病患者根据尿微量白蛋白/肌酐(ACR)分为正常白蛋白尿组(ACR＜ 30 mg/g),微量白蛋白尿组(ACR30～300 mg/g),大量白蛋白尿组(ACR＞ 300 mg/g),每组均为50例.同时选取健康体检者30名作为对照组.应用全自动生化分析仪测定空腹血糖、HbA1c、肌酐、白蛋白、甘油三酯、总胆固醇、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDH-C)等生化指标.采用酶联免疫吸附法测定血、尿脂联素水平.结果 血、尿脂联素及HbA1c水平在对照组、正常白蛋白尿组、微量白蛋白尿组及大量白蛋白尿组中依次升高,差异均有统计学意义(F=62.46,65.26,5.37,P均＜0.05);血肌酐水平随尿白蛋白水平升高依次升高,微量白蛋白尿组及大量白蛋白尿组与对照组之间比较,差异有统计学意义(F=8.25,P＜0.05),微量白蛋白尿组及大量白蛋白尿组与正常白蛋白尿组之间比较无明显统计学意义(P＞0.05);估算的肾小球滤过率(eGFR)随尿白蛋白水平升高依次降低(F=54.67,P＜0.01).Pearson相关分析显示尿脂联素与血肌酐、ACR、血脂联素、HbA1c呈正相关(r=0.66,0.61,0.62,0.35,P均＜0.05),与eGFR呈负相关(r=-0.71,P＜0.01).多元逐步回归分析发现尿脂联素与血肌酐、HbA1c、ACR、eGFR及血脂联素相关(P均＜0.05).结论 尿脂联素与糖尿病肾病的严重程度呈正相关.     

Insulin resistance and endothelial dysfunction in type 2 diabetes patients with or without microalbuminuria

OBJECTIVE: To evaluate the relationship between insulin resistance and endothelial function in type 2 diabetes patients with or without microalbuminuria and to explore the pathophysiological mechanisms of the increased macrovascular risk in type 2 diabetes mellitus. METHODS: Twelve type 2 diabetes patients with microalbuminuria (urinary albumin 30-300 g/mg creatinine, DM-MA) and 12 type 2 diabetes patients without microalbuminuria (urinary albumin <30 g/mg creatinine, DM-NA) were recruited, matched for their sex, age, body mass index (BMI), diabetes duration, antidiabetic therapy. Their hemoglobin (HbA1C) was less than 7.5% and the blood pressure was lower than 140/90 mmHg. None had evidence of macrovascular disease and serum cholesterol levels were normal. Twelve healthy volunteers (C) were enrolled as controls. All subjects received a hyperinsulinemic euglycemic clamp study (insulin infusion rate, 120 mU/m2/min) to assess the peripheral glucose disposal rate (GDR) in the steady state and had a high-resolution ultrasonography to measure vasodilation in the brachial artery diameter in response to reactive hyperemia (endothelium-dependent) and administration of glyceryl trinitrate (endothelium-independent). Plasma free fatty acids (FFAs), plasminogen activator inhibitor type I (PAI-1), and von Willebrand factor (vWF) were also measured. RESULTS: The GDR was lower in type 2 diabetes patients with microalbuminuria (7.90 +/- 1.79 mg/kg/min) than in patients without microalbuminuria (9.46 +/- 1.59 mg/kg/min, P<0.05), and the GDR in both diabetes groups was decreased, compared with the findings from the healthy control group (13.06 +/- 1.98 mg/kg/min, P<0.01). Plasma FFAs concentration was different among the three groups (DM-MA-1008 +/- 229 mol/l, DM-NA-675 +/- 201 mol/l, P<0.01; C-364 +/- 169 mol/l, P<0.01). Endothelium-dependent vasodilation was impaired in the microalbuminuric patients (8.0 +/- 3.8%) compared with the normoalbuminuria patients (9.7 +/- 4.3%, P>0.05) and the healthy controls (14.2 +/- 5.0, P<0.05). Plasma PAI-1 and vWF levels increased in the microalbuminuric patients (61.9 +/- 18.2 ng/ml, 126.8 (76.5-212.7) %) compared with the levels in the normoalbuminuric patients (45.4 +/- 16.3 ng/ml, 87.9 (84.2-114) %) (PAI-1, P<0.05; vWF, P>0.05) and in the healthy controls (33.6 +/- 10.6 ng/ml, 67.2 (61.5-75.4) %, both P<0.01). In addition, the partial correlation analysis revealed a significant positive correlation between GDR and endothelium-dependent vasodilation (r=0.465, P<0.01, n=36), and a negative correlation between GDR and plasma FFA levels (P<0.05). CONCLUSIONS: Compared with type 2 diabetes patients with normoalbuminuria, patients with microalbuminuria had more severe insulin resistance, more prominent endothelial dysfunction, and higher plasma FFA, PAI-1, and vWF levels. Therefore we speculate that insulin resistance and endothelial dysfunction may act within the metabolic syndrome to increase the cardiovasular risk in this subset of patients, and improving insulin resistance and endothelial dysfunction may reduce the morbidity and mortality from macrovascular complications in type 2 diabetes patients.     

Effect of Zinc Supplementation on Serum Homocysteine in Type 2 Diabetic Patients with Microalbuminuria

OBJECTIVES: Elevated homocysteine levels are considered to be an independent risk factor for cardiovascular complications in diabetic patients. The aim of this study was to find out if zinc supplementation improves homocysteine levels, which may exert vascular-protective effects in type 2 diabetes subjects with microalbuminuria. METHODS: In a randomized, double-blind, controlled, crossover study, 50 type 2 diabetic patients with microalbuminuria were subdivided into two groups and supplemented with 30 mg/d of zinc (group 1) or placebo (group 2) for three months with a four-week wash out period. Serum creatinine, vitamin B₁₂, folate, fasting plasma glucose, HbA1c, lipid profiles, zinc, homocysteine levels and random urine albumin were measured before and after the first and second phase of the study in all participants. RESULTS: Mean serum zinc was significantly increased after zinc supplementation (from 76 ± 16 μg/dl to 93 ± 20 µg/dl; p < 0.05), while there was no change in the placebo group (75 ± 16 µg/dl to 75 ± 15 µg/dl). With zinc supplementation, homocysteine levels reduced significantly (from 13.71 ± 3.84 μmol/l to 11.79 ± 3.06 μmol/l; p < 0.05), which did not occur on placebo (from 12.59 ± 2.13 μmol/l to 13.36 ± 2.03 μmol/l). Simple regression was used to show a positive correlation between urine albumin excretion and serum homocysteine (r = 0.37, p = 0.023). Vitamin B₁₂ and folate levels increased significantly in patients who received zinc in comparison to those who received placebo. A negative correlation was observed between homocysteine and vitamin B₁₂ concentration (r = -0.36, p = 0.025). CONCLUSION: Zinc supplementation reduced serum homocysteine and increased vitamin B₁₂ and folate concentrations in type 2 diabetic patients with microalbuminuria.     

Paternal phenotype is associated with microalbuminuria in young adults with Type 1 diabetes mellitus of short duration.

AIMS: Susceptibility to diabetic nephropathy has not yet been causally linked to any genetic factors. We investigated in nuclear families whether parental ambulatory blood pressure, lipids and urine albumin excretion were early markers of risk of microalbuminuria in young adults with Type 1 diabetes. SUBJECTS AND METHODS: A subset of 98 young adults from the Oxford Regional Prospective Study were followed from diagnosis until aged >or= 16 years and duration of diabetes >or= 5 years (probands). Of these subjects, 24 developed microalbuminuria (males >or= 3.5 mg/mmol; females >or= 4 mg/mmol) and were designated cases, whereas 74 were controls. Family medical history, 24-h ambulatory blood pressure, urine albumin to creatinine ratio (ACR), non-fasting lipid profile and apolipoproteins (A1 and B) were measured in mothers and fathers. RESULTS: The prevalence of a parental hypertension (taking anti-hypertensive medication or daytime blood pressure > 140/90 mmHg), was similar in cases and controls (29% vs. 35%; chi2 test, P = 0.3). The systolic blood pressure night to day ratio and also ACR were higher in the fathers of cases when compared with the fathers of controls [systolic 0.88 (0.08), n = 14 vs. 0.85 (0.12), n = 53, P = 0.041]; [ACR median (IQ range) 0.6 mg/mmol (0.2-16.9) vs. 0.47 mg/mmol (0.3-3.7), P = 0.049]. Paternal night-time systolic blood pressure, night to day systolic blood pressure ratio and ACR were correlated with an index of susceptibility to albuminuria (r = 0.25, P = 0.042, n = 69 and r = 0.28, P = 0.022, n = 0.67 and r = 0.24, P = 0.029, n = 0.85, respectively). CONCLUSIONS: Higher paternal ACR and night to day ratio of ambulatory blood pressure, but not parental hypertension or maternal factors, are associated with microalbuminuria in young adults with Type 1 diabetes.     

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.