FDP/尿蛋白比值检测在90例糖尿病肾病诊断中临床应用

目的研究FDP/尿蛋白比值检测在糖尿病肾病诊断中的临床意义。方法选取该院接受治疗的糖尿病肾病患者90例作为研究对象,其中FDP/尿蛋白比值大于0.1的20例患者作为观察组,FDP/尿蛋白比值小于0.5的26例患者作为对照组,对所有患者每个月进行1次随访,并使用酶联免疫吸附法检测患者的凝血、纤溶指标,观察患者尿蛋白与肾功能的变化。结果糖尿病肾病患者的FDP/尿蛋白比值与凝血、纤溶活性以及HbA1C、尿蛋白呈现出明显的正相关的关系,糖尿病肾病患者的FDP/尿蛋白比值与肾功能呈现出负相关的关系,观察组患者与对照组患者相比,观察组患者存在着明显的凝血与纤溶活性增强的状况,并且肾功能恶化速度也比较快。结论糖尿病肾病患者的FDP/尿蛋白比值不仅能够反映患者的凝血和纤溶状态,而且能够反映糖尿病肾病患者的病情状况,预测出患者肾功能的恶化速度,对于糖尿病肾病的诊断与治疗具有重要意义。     

Elevation of urinary betaig-h3, transforming growth factor-beta-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P < 0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.     

Plasma angiotensin II, renin activity and serum angiotensin-converting enzyme activity in non-insulin dependent diabetes mellitus patients with diabetic nephropathy

The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.     

Urinary N-acetyl-β-D-glucosaminidase (NAG) activity in the early detection of diabetic nephropathy

One of the serious outcomes of diabetes mellitus is nephropathy. Measurement of microalbuminuria is a routine clinical practice for screening the diabetic nephropathy, but the injury to the kidney may be happening even without microalbuminuria. The association between urinary enzyme activities of N-acetyl-β-D-glucosaminidase (NAG) and angiotensin converting enzyme (ACE) and urine microalbumin was assessed in this study to define the possible biofactor for detection of early diabetic nephropathy. Urinary enzyme activities of NAG and ACE and urine microalbumin of 24 h, serum ACE, and some other clinical features are investigated in 35 type 2 diabetic patients. Glycated hemoglobin (HbA1c), triglycerides, serum ACE, and urine NAG were significantly elevated in diabetic groups compared to the healthy controls. There was no relation between urine NAG and microalbuminuria except in the group of diabetic patients which had urine NAG activity upper than 25 IU/ml; there was a correlation between urine NAG and serum ACE. We may conclude that before the finding of microalbumin in urine, the elevated urine NAG, as an early indicator of renal damage, is associated with serum ACE which is related to kidney vascular microangiopathies.     

Heparanase activity as a prospective marker for diabetic nephropathy in Egyptian patients with type 2 diabetes mellitus

The objective of this study is to investigate the possible association between heparanase activity and diabetic and renal biomarkers to evaluate heparanase as a predictor of diabetic nephropathy in type 2 Egyptian diabetic patients. Eighty four volunteers were classified as follows: group I comprised 28 normal subjects, group II consisted of 28 type 2 diabetic patients with normoalbuminuria, and group III consisted of 28 type 2 diabetic patients with microalbuminuria. Heparanase activity in the urine and serum, diabetic biomarkers, and renal function tests were determined. Type 2 diabetic patients with normoalbuminuria exhibited a significant increase in serum heparanase activity (39.19 %); this increase was augmented in patients with microalbuminuria (122.2 %), compared to normal control. Elevation in serum heparanase activity was parallel with the levels of diabetic biomarkers. Urinary heparanase activity showed a significant increase in the type 2 diabetic patients with normoalbuminuria (49.14 %), while kidney function biomarkers were insignificantly changed with exception to a significant decrease in urinary creatinine (14.24 %), compared to normal control. On the other hand, diabetic patients with microalbuminuria showed a dramatic increase in urinary heparanase activity with a significant increase in all kidney function biomarkers, together with a highly significant decrease in creatinine and estimated glomerular filtration rate (eGFR) compared to those with normoalbuminuria. Significant positive correlation between serum heparanase activity and plasma glucose, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) as well as urinary heparanase activity and albuminuria was reported. Also, a significantly negative correlation was found between urinary heparanase and urinary creatinine and eGFR. Heparanase activity may serve as a potential predictor for diabetic nephropathy in type 2 diabetic patients with uncontrolled glucose tolerance. Therefore, the use of heparanase for early diagnosis in addition to good glycemic control would be more effective in reducing the risk of diabetic renal complications.

     

Haptoglobin gene polymorphism in type 2 diabetic patients with and without nephropathy: An Egyptian study

BACKGROUND: The development and progression of diabetic microvascular complications including nephropathy are related to the degree of glycemic control and oxidative stress and may be influenced by genetic factors. The aim of the present study was to investigate the association between haptoglobin (Hp) gene polymorphism and the occurrence of diabetic nephropathy in patients with type 2 diabetes mellitus and to find a possible link between Hp phenotypes and the inflammatory parameters; serum C-reactive protein (CRP), interleukin- 6 (IL-6), and Hp. METHODS: The study included 60 normotensive type 2 diabetic patients (>5 years duration) categorized into three equal groups (normo-, micro-, and macroalbuminuric), according to urinary albumin excretion (UAE). In addition, 20 age- and sex-matched individuals were selected to serve as a control group. Serum CRP, IL-6, and Hp concentrations were measured and Hp phenotyping was conducted using polyacrylamide gel electrophoresis. RESULTS: The frequency of Hp phenotype 1-1 (Hp 1-1) in diabetic patients with normoalbuminuria was 7/20 (35%) as compared with 1/20 (5%) in diabetics with macroalbuminuria (p=0.02). However, the frequency of Hp 2-2 was greater in diabetics with macroalbuminuria (12/20, 60%) than in those with normoalbuminuria or controls (5/20, 25%; p=0.03). Patients with diabetic nephropathy (micro- or macroalbuminuria) had higher levels of serum CRP, IL-6, and Hp than those without nephropathy (normoalbuminuria). Serum Hp levels in type 2 diabetics were higher in Hp phenotype 2-2 than in Hp 1-1; however, serum CRP and IL-6 levels did not differ significantly between Hp phenotype groups. Moreover, there were significant positive correlations between UAE and serum levels of CRP, IL-6, and Hp in diabetic patients. CONCLUSIONS: Hp phenotype 2-2 is considered to be a major susceptibility gene for the development of nephropathy in type 2 diabetic patients. In addition, the significant association between inflammatory parameters and UAE indicates that inflammation may be a pathogenic mechanism of renal injury in type 2 diabetics. Moreover, serum IL-6 and Hp may be good prognostic factors for the development of nephropathy in the course of diabetes mellitus. Future research on the use of anti-inflammatory therapy may result in a new approach to the treatment and prevention of diabetic nephropathy.     

Serum enzymes of lysosomal origin as indicators of the metabolic control in diabetes: Comparison with glycated hemoglobin and albumin

Summary Several lysosomal enzymes (β-N-D-acetylglucosaminidase, β-D-glucoronidase, α-D-galactosidase, β-D-galactosidase, α-L-fucosidase, α-D-glucosidase, α-D-mannosidase, β-D-glucosidase), glycated albumin and glycated hemoglobin (HbA_1c) were determined in the serum of 81 insulin-dependent diabetics with different degrees of metabolic control (optimal, 21 patients; good, 39 patients; poor, 21 patients) and without signs of complications, and in 42 control subjects. All parameters examined increased in serum in inverse proportion to the degree of metabolic control. A highly significant correlation (p<0.01) was found between lysosomal enzymes and both glycated albumin and HbA_1c. All parameters correlated with hyperglycemia, glycated albumin having the highest γ-value (0.586) and lysosomal enzymes the lowest one. Unlike glycated albumin and HbA_1c, serum levels of lysosomal enzymes in patients with optimal metabolic control were undistinguishable or even lower than those of controls. A 2-month longitudinal monitoring of a patient who was hospitalized in conditions of poor metabolic control and adequately treated, proved that lysosomal enzymes diminished in serum parallel to glycated albumin and HbA_1c in relation to improvement of the metabolic situation. The conclusion is drawn that serum lysosomal enzymes are good indicators of the metabolic control of diabetic patients probably reflecting the overall metabolic state connected with insulin action rather than hyperglycemia.     

多项检测指标在2 型糖尿病早期肾损伤中的诊断价值

目的 分析尿白蛋白/ 肌酐比值(ACR)、尿α1-微球蛋白(α1-MG)、尿β2-微球蛋白(β2-MG)和血清胱抑素C(CysC)在2 型糖尿病早期肾损害中的诊断价值。方法 选取2019 年5 月至2020 年1 月芜湖市中医医院收治的2 型糖尿病患者108 例,根据尿蛋白排出率(UAER)将患者分为单纯糖尿病组(UAER <30 mg/ 24 h)68 例和糖尿病肾病组(30 mg/ 24 h≤UAER<300 mg/ 24 h)40 例。并选取同期健康体检者30 例为健康对照组。观察各组尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平并进行统计学比较。绘制受试者工作特征(ROC)曲线预测各指标对早期糖尿病肾损伤的曲线下面积(AUC),并计算各指标的敏感度和特异度。结果 糖尿病肾病组和单纯糖尿病组的尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平明显高于健康对照组(P 均<0. 05)。糖尿病肾病组的尿ACR、尿α1-MG、尿β2-MG 和血清CysC 水平明显高于单纯糖尿病组(P 均<0. 05)。尿ACR、尿α1-MG、尿β2-MG 和血清CysC的曲线下面积分别为0. 923、0. 851、0. 755 和0. 702,敏感度分别为84. 4%、75. 0%、71. 9%和62. 5%,特异度分别为96. 4%、85. 5%、81. 8%和67. 3%。结论 尿ACR、尿α1-MG、尿β2-MG 和血清CysC 在糖尿病早期肾损伤的进程中有着重要的作用,其测定有助于糖尿病肾病的早期诊断,为临床诊治提供可靠的依据。     

Heparanase activity as a prospective marker for diabetic nephropathy in Egyptian patients with type 2 diabetes mellitus

The objective of this study is to investigate the possible association between heparanase activity and diabetic and renal biomarkers to evaluate heparanase as a predictor of diabetic nephropathy in type 2 Egyptian diabetic patients. Eighty four volunteers were classified as follows: group I comprised 28 normal subjects, group II consisted of 28 type 2 diabetic patients with normoalbuminuria, and group III consisted of 28 type 2 diabetic patients with microalbuminuria. Heparanase activity in the urine and serum, diabetic biomarkers, and renal function tests were determined. Type 2 diabetic patients with normoalbuminuria exhibited a significant increase in serum heparanase activity (39.19 %); this increase was augmented in patients with microalbuminuria (122.2 %), compared to normal control. Elevation in serum heparanase activity was parallel with the levels of diabetic biomarkers. Urinary heparanase activity showed a significant increase in the type 2 diabetic patients with normoalbuminuria (49.14 %), while kidney function biomarkers were insignificantly changed with exception to a significant decrease in urinary creatinine (14.24 %), compared to normal control. On the other hand, diabetic patients with microalbuminuria showed a dramatic increase in urinary heparanase activity with a significant increase in all kidney function biomarkers, together with a highly significant decrease in creatinine and estimated glomerular filtration rate (eGFR) compared to those with normoalbuminuria. Significant positive correlation between serum heparanase activity and plasma glucose, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) as well as urinary heparanase activity and albuminuria was reported. Also, a significantly negative correlation was found between urinary heparanase and urinary creatinine and eGFR. Heparanase activity may serve as a potential predictor for diabetic nephropathy in type 2 diabetic patients with uncontrolled glucose tolerance. Therefore, the use of heparanase for early diagnosis in addition to good glycemic control would be more effective in reducing the risk of diabetic renal complications.     

Glycosylated serum proteins in diabetic patients and their relation to metabolic parameters

Glycosylated plasma proteins (GSP) and some metabolic parameters (plasma glucose profile, urine glucose excretion, glycosylated hemoglobin, cholesterol, triglycerides) were evaluated in 70 diabetic and 70 normal subjects. Of the late diabetic complications, retinopathy, nephropathy and somatic neuropathy were evaluated. Proliferative retinopathy was observed in 41 of the 70 diabetics studied. No retinopathy or background retinopathy was observed in 29 diabetics. Nephropathy was diagnosed in 39 patients and somatic neuropathy in 44 patients; 26 diabetic subjects had no complications. GSP levels were 0.82 +/- 0.03 nmolHMF/mg prot in diabetics and 0.43 +/- 0.02 nmolHMF/mg prot in controls. GSP levels were positively correlated with metabolic parameters evaluated the same day and 14 days before. A positive correlation between GSP and triglycerides was seen for the first time. The patients with retinopathy showed levels of GSP significantly higher (p less than 0.001) in respect to patients with background retinopathy or absence of it (0.91 +/- 0.03 vs 0.74 +/- 0.04 nmolHMF/mg prot). GSP were significantly higher in the patients with somatic neuropathy (0.93 +/- 0.02 nmolHMF/mg prot) (p less than 0.001) than in the subjects without neuropathy (0.72 +/- 0.04 nmolHMF/mg prot). GSP levels were 0.92 +/- 0.03 nmolHMF/mg prot in diabetics with proteinuria and 0.75 +/- 0.04 nmolHMF/mg prot in diabetics without proteinuria (p less than 0.001). These results confirm the importance of GSP determination as another parameter of glycemic control and particularly as an index of the overall protein glycosylation processes.