Severity of glomerulopathy predicts long-term urinary albumin excretion rate in patients with type 1 diabetes and microalbuminuria.

OBJECTIVE: To investigate whether the degree of glomerular structural lesions in young patients with type 1 diabetes and microalbuminuria was associated with urinary albumin excretion rate (AER) 6 years later and whether the AER level was influenced by blood glucose control, blood pressure, or glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS: There were 17 young adults with type 1 diabetes and microalbuminuria, 8 men and 9 women with mean age 20 years (95% CI: 18-22) and duration of diabetes of 11 years (10-13), who participated in a 6-year prospective study. Kidney biopsies (measurements of basement membrane thickness [BMT] and mesangial and matrix volume fractions) and GFR were performed at baseline. AER and HbA1c were measured at least three times a year and blood pressure once a year. RESULTS: In a multivariate analysis, baseline BMT and mean 6-year HbA1c contributed significantly to AER at the end of the study (R2 = 0.69, P < 0.01). When mesangial volume fraction replaced BMT as the independent variable, this parameter and AER at baseline predicted the AER at 6 years (R2 = 0.55, P < 0.55). Mesangial volume fraction and BMT (in separate analysis) contributed significantly to change in AER during the study. During the study, neither AER (30 micrograms/min [19-40] to 16 micrograms/min [7-90]) nor blood pressure (96 mmHg [92-102] to 95 mmHg [91-98]) changed significantly in the group. However, HbA1c was reduced from 10.3 (9.6-11.0) to 8.4% (7.8-9.1) (P < 0.01). CONCLUSIONS: In young patients with microalbuminuria, the long-term urinary AER was predicted by the degree of glomerular structural changes and associated with blood glucose control, but not with blood pressure or GFR.     

Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes

Objective. In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. Material and methods. We performed a cross‐sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary orosomucoid was measured using a particle‐enhanced immunoturbidimetric assay. Plasma interleukin‐6 (IL‐6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule‐1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants. Results. Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (p<0.001), C‐reactive protein (CRP) (p<0.001), IL‐6 (p<0.001), tPA (p<0.003) and sICAM (p<0.003) compared with healthy controls. In patients with type 2 diabetes, UOER was independently associated with increasing values of IL‐6 (1.43 (1.06–1.93)) and tPA (1.82 (1.20–2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction. Conclusions. Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low‐grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low‐grade inflammation and early endothelial dysfunction.     

Increased plasma apolipoprotein B-containing lipoproteins associated with increased urinary albumin within the microalbuminuria range in type 2 diabetes

BACKGROUND: While increased plasma concentrations of apolipoprotein B-containing lipoproteins are a feature of diabetic nephropathy associated with nephrotic range proteinuria, the relationship of plasma lipoproteins to increasing urine albumin concentration within the microalbuminuria range is less well-studied. METHODS: We, therefore, examined the relationship between urine albumin excretion in the 0 to 100 mg/L range and plasma lipoproteins in 56 Oji-Cree with type 2 diabetes. RESULTS: We found a significant direct relationship between the urinary albumin concentration within this low range and the plasma concentrations of total and low density lipoprotein cholesterol and apolipoprotein B (p = 0.015, 0.0032, and 0.0019, respectively). CONCLUSIONS: These results suggest that the well-known relationship between gross proteinuria and hyperlipidemia may extend into the microalbuminuric range in subjects with type 2 diabetes.     

Increased urinary excretion of the retinol-binding protein in insulin-dependent diabetes mellitus in the absence of microalbuminuria

Urinary excretion of the retinol-binding protein (RBP) was studied in 36 insulin-dependent diabetics with serum creatinine concentrations within the normal range and no microalbuminuria. The excretion was significantly (p < 0.05) higher in the diabetics as compared to a group of apparently healthy persons. The diabetes control indices HbA₁ and serum fructosamine showed no correlation to the rate of urinary RBP excretion. The present data support the idea that tubular dysfunction may be an early symptom of diabetic nephropathy.     

Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and microalbuminuria.

OBJECTIVE: In patients with type 2 diabetes, microalbuminuria is associated with an increase in predominantly cardiovascular mortality. Considerable interindividual variability in the rate of progression of microalbuminuria exists. The prognostic significance of rate of progression of microalbuminuria with regard to cardiovascular and renal clinical end points is, however, unknown. The purpose of this study was to determine the prognostic significance of rate of progression of microalbuminuria for cardiovascular end points and renal function. RESEARCH DESIGN AND METHODS: In a previous prospective cohort study, progression of microalbuminuria (expressed as mean yearly change in albumin-to-creatinine ratio) was assessed in 58 patients with type 2 diabetes. During a median follow-up of 7 years after progression of microalbuminuria was determined, we registered all-cause mortality and coronary heart disease mortality as primary end points and coronary heart disease (fatal or nonfatal), peripheral vascular disease, ischemic stroke, retinopathy, macroalbuminuria, and change in serum creatinine as secondary end points. RESULTS: Seven subjects died during the study; five of these subjects died of coronary heart disease. Cox's regression analysis identified progression of microalbuminuria as a significant predictor of all-cause mortality (hazard ratio 1.46 per point increase in albumin-to-creatinine ratio per year, P < 0.001), coronary heart disease mortality (hazard ratio 2.32, P = 0.006), and macroalbuminuria (hazard ratio 1.79, P < 0.001). Adjustment for multiple cardiovascular risk factors did not affect these results. Identical analyses for baseline level of microalbuminuria instead of progression rate of microalbuminuria did not show significant hazard ratios. In addition, progression of microalbuminuria significantly predicted an increase in serum creatinine (r = 0.29, P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and microalbuminuria, the rate of progression of albumin excretion seems to be a powerful independent predictor of mortality caused mainly by coronary heart disease.     

2型糖尿病患者尿白蛋白排泄率与血脂的关系

目的探讨2型糖尿病患者尿白蛋白排泄率与血脂的关系。方法无尿路感染及原发性肾脏疾病病史的2型糖尿病患者68例,按尿白蛋白排泄率分为正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组。检测所有患者的空腹血糖、糖化血红蛋白、血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇。结果微量白蛋白尿组和大量白蛋白尿组空腹血糖、糖化血红蛋白、收缩压和舒张压均高于正常白蛋白尿组;大量白蛋白尿组的空腹血糖、糖化血红蛋白、收缩压和舒张压均较微量白蛋白尿组高。微量白蛋白尿组和大量白蛋白尿组血清甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平均高于正常白蛋白尿组;大量白蛋白尿组血清甘油三酯、总胆固醇和低密度脂蛋白胆固醇较微量白蛋白尿组高。3组血清高密度脂蛋白胆固醇水平无统计学意义(P>0.05)。结论2型糖尿病患者尿白蛋白排泄率不仅与糖代谢指标和血压有关,与血脂也存在相关性,提示脂质代谢紊乱在糖尿病肾病的发生、发展中可能起一定的作用。     

Increased urinary excretion of L-xylulose in patients with liver cirrhosis.

The urinary excretions of L-xylulose, xylitol and D-glucarate after the oral administration of glucuronolactone (5 g) were measured in normal healthy persons, patients with diabetes mellitus, acute hepatitis in recovery stage, chronic hepatitis and liver cirrhosis. In normal subjects, the mean value of L-xylulose excretion was 14.6 +/- 1.4 mumol/2 h with a range from 6.5 to 21.8. Marked increase of L-xylulose excretion was observed in cirrhotic patients, the mean value was 97.1 +/- 19.8 with a range from 22.0 to 236.6. Though some cases of acute and chronic hepatitis showed higher values than the normal range, no case exceeded 50 mumol/2 h. The urinary excretion of xylitol in cirrhotic patients was also higher than normal no increase was observed in D-glucarate excretion. The values of L-xylulose excretion in cirrhosis were correlated with the values of serum total bilirubin, albumin, albumin/globulin ratio, lactate dehydrogenase and prothrombin time. These findings indicate that the measurement of L-xylulose in urine after the oral glucuronolactone loading provides a useful tool for evaluation of the severity of liver cirrhosis.     

2型糖尿病患者血同型半胱氨酸与踝肱指数及微量尿白蛋白关系的研究

目的探讨2型糖尿病（T2DM）患者血同型半胱氨酸（Hcy）与踝肱指数（ABI）及微量尿白蛋白（U-mAlb）的相关性。方法将90例2型糖尿病病患者按照Hcy水平的不同分为两组：高Hcy组为血Hcy〉10.5μmol/L,低Hcy组为血Hcy≤10.5μmol/L,分别测定踝臂指数（ABI）、U-mAlb。结果高Hcy组ABI明显低于低Hcy组（P〈0.05）,Hcy与ABI呈显著负相关,而U-mAlb高于低Hcy组（P〈0.01）。结论高同型半胱氨酸血症与糖尿病患者血管病变关系密切。     

2型糖尿病患者血脂水平与尿清蛋白排泄量的关系

目的 探讨2型糖尿病患者血脂水平以及血压与患者尿清蛋白排泄量的关系.方法 选取97例2型糖尿病患者,按照尿清蛋白排泄量分为大量清蛋白尿、微量清蛋白尿和对照清蛋白尿3组,分别测定空腹血糖、三酰甘油、总胆固醇、肌酐4项生化指标并测量血压,作组间比较.结果 除肌酐外,大量清蛋白尿组空腹血糖、三酰甘油、总胆固醇及舒张压、收缩压均明显高于微量清蛋白尿组,微量清蛋白尿组高于对照清蛋白尿组.结论 2型糖尿病患者血脂水平与尿清蛋白排泄量关系密切,提示脂质代谢紊乱对2型糖尿病及糖尿病肾病并发症的发生、发展具有促进作用.     

2型糖尿病患者踝肱指数与微量尿白蛋白及高尿酸血症的关系

目的探讨2型糖尿病患者踝肱指数（ABI）与微量尿白蛋白（U-mAlb）及高尿酸血症的相关性。方法检测180例2型糖尿病患者的ABI、U-mAlb、血尿酸（SUA）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、体质量指数（BMI）等,分析ABI与U-mAlb、高尿酸血症及其他常规血生化指标的相关性。结果微量尿白蛋白组、大量尿白蛋白组与正常尿白蛋白组比较,患者糖尿病病程较长（9.0±5.7）年、（10.6±7.4）年vs（6.1±4.3）年（均P〈0.01）,ABI值较低0.84±0.15、0.76±0.13 vs 1.02±0.13（均P〈0.01）,ABI与U-mAlb呈明显负相关（P〈0.05）。SUA升高组与SUA正常组ABI差异无统计学意义（P〉0.05）。结论尿白蛋白增加是2型糖尿病患者外周血管病变的独立相关因素,高尿酸血症不是其独立相关因素。异常ABI具有重要预警意义,不仅是外周血管功能状态的反映,还能一定程度体现肾脏血管损害情况。     

Increased urinary excretion of beta-hydroxyisovaleric acid in ketotic and non-ketotic type II diabetes mellitus

To evaluate the catabolism of leucine in diabetes mellitus, the urinary excretion of beta-hydroxyisovaleric acid, a by-product of leucine catabolism, in 21 nonproteinuric type II diabetic patients with and without ketosis and 21 control subjects was measured using gas chromatography-mass spectrometry. Urinary beta-hydroxyisovaleric acid and serum leucine concentrations were higher in the 9 ketotic diabetic patients than in the 12 nonketotic diabetic patients (p less than 0.005, p less than 0.01, respectively) or in the control subjects (p less than 0.01, p less than 0.01, respectively). The serum leucine concentrations in the nonketotic diabetic patients and control subjects did not differ significantly (p greater than 0.05), but urinary beta-hydroxyisovaleric acid concentrations were significantly greater in the former (p less than 0.01). These data suggest that in type II diabetic patients the catabolism of leucine is accelerated even in the absence of ketosis and that the urinary beta-hydroxyisovaleric acid concentration is a useful marker of short-term metabolic control in these patients.     

Increased intracranial arterial resistance in patients with type 2 diabetes mellitus.

BACKGROUND: The majority of the studies investigating risk factors for stroke have focused on the atherosclerosis of extracranial carotid arteries. Risk factors for the involvement of intracranial arteries in patients with stroke have not been widely investigated so far. The pulsatility index reflects the vascular resistance of intracranial arteries and could therefore be used as an estimate of the severity of vascular damage. MAIN PURPOSE: The present study aimed to examine the influence of type 2 diabetes mellitus and some other atherosclerosis risk factors on intracranial vascular resistance in patients with a previous stroke or transient ischemic attack. METHODS: Transcranial doppler investigations were performed in 103 patients with previous stroke (31 with diagnosis of type 2 diabetes, 72 without diabetes), at least 3 months after stroke occurred. Blood flow velocities of anterior cerebral arteries, middle cerebral arteries, the intracranial part of vertebral arteries and the basilar artery, as well as of the extracranial part of the internal carotid artery were measured, and Gosling's pulsatility index was calculated. The maximal pulsatility index of intracranial arteries was defined to express the most pronounced damage. RESULTS: Diabetic patients had a significantly higher pulsatility index than non-diabetic patients in all examined intracranial arteries. The maximal pulsatility index was also significantly higher in diabetic patients than in non-diabetic patients (1.24 +/- 0.25 vs. 1.00 +/- 0.23; p < 0.0001). There was no significant difference in the pulsatility index between men and women and between groups of patients with or without hypertension. In the multivariate analysis, the presence of diabetes (p < 0.0001) and the age of patients (p < 0.0001) were the only factors significantly predicting maximal pulsatility index, and this relationship was independent on the presence of hypertension. CONCLUSIONS: Diabetic patients with previous stroke have a higher pulsatility index than non-diabetic patients with previous strokes, which indicates a higher increase in intracranial arterial resistance and more severe damage to cerebral blood flow in diabetes mellitus.     

Cardiovascular autonomic neuropathy is associated with microalbuminuria in older patients with type 2 diabetes

OBJECTIVE: Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients. RESEARCH DESIGN AND METHODS: At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 +/- 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording. RESULTS: Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest tertile of HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with urine microalbumin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA(1c), and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other. CONCLUSIONS: Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes.     

Increased urinary excretion of argininosuccinate in type II citrullinemia

Although argininosuccinate is a product of the catalytic action of deficient argininosuccinate synthetase in citrullinemia, its concentration was found to be elevated in the urine of patients with type II citrullinemia. Urinary argininosuccinate was identified by two methods; its conversions to anhydride by boiling in an acidic solution and to arginine by the enzymatic action of argininosuccinate lyase. Oral administration of citrulline to patients with type II citrullinemia and control subjects increased urinary argininosuccinate levels.

These phenomena are consistent with our previous findings on type II citrullinemia (Adv Exp Med Biol 1983;153:63–76, J Clin Biochem Nutr 1986;1:129–142), namely that renal argininosuccinate synthetase which plays a role in arginine synthesis is not deficient in patients with type II citrullinemia; and that serum arginine levels in patients with type II citrullinemia are rather higher than the controls, and increase after the oral administration of citrulline.

The organ-specific deficiency of argininosuccinate synthetase in type II citrullinemia is further confirmed by this paper.