~（99m）Tc－DTPA肾动态显像测定GFR对糖尿病肾病早期诊断的价值

应用￣（９９ｍ）Ｔｃ－ＤＴＰＡ肾动态显像测定６１例ＮＩＤＤＭ的肾小球滤过率（ＧＦＲ），并与相配对的２０例正常人作比较。结果表明无蛋白尿的糖尿病患者ＧＦＲ，升高率为３５％，且与血糖呈正相关。提示￣（９９ｍ）Ｔｃ－ＤＴＰＡ肾动态显像测定ＧＦＲ可作为糖尿病肾病最早期诊断的检测手段。ＮＩＤＤＭ早期确实存在肾小球高滤状态．ＧＦＲ＞１４０ｍｌ／ｍｉｎ可作为糖尿病肾病发生的预兆指标。     

糖尿病肾病尿唾液酸变化的临床意义

采用Ｆ－８３３６化学比色法，测定了６９例不同白蛋白排泄率（ＡＥＲ）的非胰岛素依赖性糖尿病（ＮＩＤＤＭ）病人及１９例正常人的２４小时尿总唾液酸（ＵＴＳＡ），结果显示：①微量白蛋白尿组ＵＴＳＡ水平明显高于正常对照组及正常白蛋白尿组（均Ｐ＜０．０１）。②伴随尿中白蛋白排泄率增加，尿ＵＴＳＡ值也呈正相关的增加。从而提示ＵＴＳＡ不仅可作为糖尿病肾病（ＤＮ）的早期诊断指标；在一定程度上也反映ＤＮ的肾脏损伤程度。     

^99mTc—DTPA肾动态显像测定GFR对糖尿病肾病早期诊断的价值

应用＾９９ｍＴｃ－ＤＴＰＡ肾动态显像测定６１例ＮＩＤＤＭ的肾小球滤过率（ＧＦＲ），并与相配对的２０例正常人作比较。结果表明无蛋白尿的糖尿病患者ＧＦＲ，升高率为３５％，且与血糖呈正相关。提示＾９９ｍＴｃ－ＤＴＰＡ肾动态显像测定ＧＦＲ可作为糠尿病肾病最早期诊断检测手段。ＮＩＤＤＭ早期确实存在肾小球高滤状态，ＧＦＲ〉１４０ｍｌ／ｍｉｎ可作为糖尿病肾病发生的预兆指标。     

NIDDM患者早期肾血流动力学及尿6－keto－PGF_（1α）、TXB_2的变化

对血压正常、多次尿蛋白定性阴性、２４小时尿微白蛋白排泄（ＵＡＥ）＜６０μｇ／ｍｉｎ、无眼底病变的２９例早期ＮＩＤＤＭ患者，测定了肾小球滤过率（ＧＦＲ）、有效肾血浆流量（ＥＲＰＦ）、肾滤过分数（ＦＦ）、尿６－ｋｅｔｏ－ＰＧＦ１α及ＴＸＢ２的变化。发现早期ＮＩＤＤＭ患者ＧＦＲ、ＦＦ增高，同时尿６－ｋｅｔｏ－ＰＧＦ１α也明显增加，而ＥＲＰＦ、尿ＴＸＢ２无明显变化，提示ＮＩＤＤＭ早期肾血流动力学变化与肾前列腺素的代谢异常有关。     

新诊断的NIDDM和IGT患者的早期肾功能改变

本文研究了６３例新诊断的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者和１６例糖耐量减低（ＩＧＴ）患者的早期肾功能改变，显示ＮＩＤＤＭ患者早期存在肾小球滤过率（ＧＦＲ）升高，肾脏体积增大和尿白蛋白排泄率（ＵＡＥ）轻度增高；１６例ＩＧＴ患者的ＧＦＲ也高于正常对照组。３４例ＮＩＤＤＭ患者经饮食控制和／或口服降糖药治疗４个月后进行了复查，结果显示：１２例代谢改善者的ＧＦＲ、肾脏体积和ＵＡＥ有不同程度的恢复；２２例代谢无改善者的ＧＦＲ有所升高，肾脏体积和ＵＡＥ则无明显变化。     

老年NIDDM患者尿液N－乙酰－β－D－氨基葡萄糖苷酶变化的临床评价

对９６例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者尿液Ｎ－乙酰－β－Ｄ－氨基葡萄糖苷酶（ＮＡＧ）的变化作了临床研究。结果显示：老年患者（６２例）尿液ＮＡＧ排出量（３２．２０±３．８０Ｕ／ｇ·Ｃｒ）高于健康对照组（３２例，７．０１±０．４２Ｕ／ｇ·Ｃｒ）及非老年患者（３４例，１８．８３±２．５７Ｕ／ｇ·Ｃｒ）（Ｐ均＜０．０１）。其增高程度与蛋白尿、糖尿病病程、视网膜微血管病变关系密切。对老年糖尿病患者尿ＮＡＧ水平的观察可作为识别是否合并早期糖尿病肾病的指标之一。     

Ⅱ型糖尿病血管并发症与血浆脂蛋白及体液免疫水平的关系

本文测定了５４例Ⅱ型糖尿病（ＮＩＤＤＭ）病人（２０例有微血管病变、１８例有大血管病变、１６例无血管病变）及３３例正常人的血浆脂蛋白（ａ）［Ｌｐ（ａ）］、低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）、循环免疫复合物（ＣＩＣ）、补体Ｃ３（Ｃ３）和免疫球蛋白。ＮＩＤＤＭ各组与正常对照组比较，ＬＤＬ－Ｃ、ＤＩＣ、Ｃ３、ＩｇＧ、ＩｇＡ水平均显著升高，ＩｇＭ显著下降。Ｌｐ（ａ）、ＣＩＣ在ＮＩＤＤＭ并发血管病变组均显著高于无血管病变组．ＮＩＤ－ＤＭ并发微血管病变组的ＣＩＣ水平又显著高于其大血管病变组。另外ＮＩＤＤＭ病人血浆Ｌｐ（ａ）、ＬＤＬ－Ｃ与ＣＩＣ水平呈显著正相关。提示ＮＩＤＤＭ病人的脂代谢异常及免疫异常与其血管并发症关系密切，脂代谢与免疫异常有内在联系。     

非胰岛素依赖性糖尿病尿α_1-微球蛋白、THP与肾小管功能的研究

为探讨ＮＩＤＤＭ肾病各期肾小管各节段功能变化，用放射免疫分析法（ＲＩＡ）测定２０例健康对照者及６２例非胰岛素依赖性糖尿病（ＮＩＤＤＭ）患者尿白蛋白排泄率（ＵＡＥＲ），尿α１－微球蛋白（α１－ＭＧ）排泄率（Ｕα１ＥＲ）及尿Ｔａｍｍ－Ｈｏｒｓｆａｌ蛋白（ＴＨＰ）排泄率（ＵＴＨＥＲ）。结果：①Ｕα１ＥＲ均值各组间比较结果：正常白蛋白尿组（ＤＭ－Ⅲ）较健康对照组（Ｃ组）升高无统计学意义（Ｐ＞０．０５），但ＤＭ－Ｉ组中，有９例（３５％）Ｕα１１ＥＲ显著升高（Ｐ＜０．０５）；微量白蛋白尿组（ＤＭ－Ⅱ）较ＤＭ－Ｉ组显著增高（Ｐ＜０．０５）。②ＵＴＨＥＲ最大均值位于大量白蛋白尿组（ＤＭ－Ⅲ）组，较Ｃ组显著降低（Ｐ＜０．０５）；最小均值位于ＤＭ－Ⅱ组与Ｃ组比较ＵＴＨＥＲ无显著性差异（Ｐ＞０．０５）。提示：①ＮＩＤＤＭ微量白蛋白尿期即可伴肾小管功能损伤且部分患者Ｕα１ＥＲ、ＵＴＨＥＲ增高先于ＵＡＥＲ的改变而反映肾脏受累。②ＮＩＤＤＭ肾小管功能损伤既有近曲小管重吸收功能障碍，亦存在髓袢合成、分泌功能异常。③联合检测ＵＡＥＲ、ＵＴＨＥＲ、Ｕα１ＥＲ有助于临床早期、全面判断ＮＩＤＤＭ肾脏病变部位及程度。     

Ⅱ型糖尿病合并高血压患者高胰岛素血症和舒血管前列腺素关系的探讨

对２３例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者、１８例ＮＩＤＤＭ合并高血压的和平共１８例正常人在糖耐量试验期间血胰岛素、６－酮－前列腺素Ｆ＿（１α）（６－ｋｅｔｏ－ＰＧＦ＿（１α）和前列腺素Ｅ＿２（ＰＧＥ＿２）水平进行了测定。ＮＩＤＤＭ并高血压组基值和糖负荷后血清胰岛素水平显著升高，６－ｋｅｔｏ－ＰＧＦ＿（１α）和ＰＧＥ＿（２）浓度显著下降，尤以胰岛素释放高峰为明显。胰岛素与６－Ｋｅｔｏ－ＰＧＦ＿（１α）浓度呈显著负相关。提示ＮＩＤＤＭ合并高血压可能与高胰岛素血症抑制舒血管前列腺素合成有关。     

Ⅱ型糖尿病人治疗前,后血浆vWF与抗凝血酶Ⅲ活性的检测

目的：探讨Ⅱ型糖尿病病人的糖化血红蛋白（ＨＢＡ１Ｃ）与血管性假血友病因子（ｖＷＦ）、抗凝血酶Ⅲ（ＡＴ－Ⅲ）的关系。方法：对２５例病人治疗前、后乐ＨＢＡ１Ｃ,ｖＷＦ及ＡＴ－Ⅲ进行了测定。结果：ＮＩＤＤＭ病人ＨＢＡ１Ｃ正常后,ｖＷＦ显下降,ＡＴ－Ⅲ显升高量均未达到正常。结论：ＮＩＤＤＭ病人ＨＢＡ１Ｃ得到控制后仍应继续进行抗血管病变及抗凝治疗。     

Correlation of urinary albumin and beta-2-microglobulin and growth hormone excretion in patients with diabetes mellitus and short stature

We examined the correlation between urinary GH, urinary albumin, and beta-2-microglobulin excretion to determine how the excretion of GH relates to markers of renal glomerular and tubular function. Urinary albumin and GH excretion was determined in timed daytime and nighttime urine collections obtained from both subjects with diabetes mellitus and subjects with short stature. For subjects with diabetes, urinary GH excretion rate correlated highly with urinary albumin concentration and excretion rate in both the range of 0 to 1.6 g/L (r = 0.75), P less than 0.001) and in the microalbuminuria range, 0 to 0.4 g/L (r = 0.53, P less than 0.001). Changes in GH and albumin excretion occurred in parallel in 71% of the subjects with diabetes and elevated albumin excretion. The mean GH excretion rate was higher in the group with elevated albumin excretion rate (AER) during both day and night compared to the group with microalbuminuria during the day and normal AER at night. For subjects with short stature, the mean albumin excretion rate was 0.7 +/- 1.3 micrograms/min (range 0.05-8.3 micrograms/min) using a sensitive enzyme-linked immunosorbent assay to measure albumin concentration. The correlation of GH and albumin excretion rates for the subjects with short stature was not statistically significant (r = 0.14, P less than 0.5). About half of the subjects with diabetes and elevated AER (greater than 10 micrograms/min) had a GH excretion rate within the range observed in subjects with short stature. The GH and albumin excretion rate were not correlated in this group. There was a positive correlation of both albumin and GH excretion rate with age in the subjects with diabetes. Urinary GH and beta-2-microglobulin excretion rates were determined in a larger group of subjects with diabetes and a separate group with short stature. Urinary GH and beta-2-microglobulin excretion were correlated both in subjects with diabetes (r = 0.46, P less than 0.001) and with short stature (r = 0.64, P less than 0.001). The association was present in urine collected either during the day or night. The mean GH excretion rate of the group with diabetes was greater than the group with short stature. In conclusion, there was an association of urinary GH and albumin excretion rate in subjects with abnormal glomerular function as indicated by elevated albumin excretion rate. An association of urinary GH and beta-2-microglobulin excretion was observed in subjects with normal tubular function.(ABSTRACT TRUNCATED AT 400 WORDS)     

晨尿微量白蛋白浓度检测对筛检早期糖尿病肾病的临床价值

目的探讨晨尿微量白蛋白浓度检测对筛选早期糖尿病肾病的临床价值.方法110例2型糖尿病病人纳入研究,收集晨尿及24 h尿样,检测晨尿微量白蛋白浓度和24 h尿白蛋白排泄率(UAER),并绘制晨尿白蛋白浓度受试者工作曲线(ROC).结果晨尿微量白蛋白浓度与UAER相关(r=0.93,P＜0.001).晨尿微量白蛋白浓度的ROC 100%敏感度截断点微量白蛋白浓度值为10 mg/L(特异度为69%),敏感度与特异度最佳截断点微量白蛋白浓度值为25mg/L(敏感度90%,特异度88%).结论晨尿微量白蛋白浓度检测对于筛选早期糖尿病肾病准确性较高.且较UAER简便、经济,可作为筛检2型糖尿病早期肾病的方法之一.     

NIDDM患者转铁蛋白尿和慢性并发症的关系

将７０例ＮＩＤＤＭ患者分成高转铁蛋白尿组和正常转铁蛋白尿组（每组３５例），比较两组的并发症发生情况。结果：两组血糖控制情况基本相同；高转铁蛋白尿组年龄较大、病程较长、体重指数较大，血压较高、尿微量白蛋白排泄率明显增加，且与微量转铁蛋白尿指数呈正相关，心脏植物神经功能异常程度和眼底病变发生率也较严重，胰岛素浓度和Ｌｐ（ａ）水平也明显升高。提示转铁蛋白尿是糖尿病慢性并发症的信号。     

Changes in the glomerular pore size selectivity in patients with type II diabetes mellitus

We measured the urinary excretion rate and clearance of three plasma proteins, albumin, transferrin, and IgG4, each of which has a similar isoelectric point, but a different molecular weight. This study consisted of 86 patients with type II diabetes mellitus and 15 healthy subjects. In the patients, the degree of the urinary excretion rate and clearance of both transferrin (TER and Ctrans) and IgG4 (IgG4 ER and CIgG4) closely correlated with that of the urinary excretion rate of albumin (AER). Although significant increases in the medians of TER and Ctrans were found even in the patients with AER of less than 5 μg/min, significant increases in the medians of IgG4 ER and CIgG4 were observed only in the patients with AER of more than 10 μg/min, in comparison with age-matched healthy subjects. Considering the biochemical properties of these proteins, our results indicate that an alteration in the glomerular size selectivity may appear even in patients with normoalbuminuria, and in patients with AER of more than 10 μg/min, more extensive damage in glomerular size selectivity may occur.     

Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration

BACKGROUND: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. RESULTS: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.     

Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary Altered filtration of macromolecules due to decreased electrical charge of the glomerular basement membrane might be the initial step in the development of albuminuria in patients with Type 1 (insulin-dependent) diabetes mellitus. We therefore investigated the selectivity index, i. e. renal clearance of non-glycated plasma albumin/clearance of glycated plasma albumin in 38 patients with Type 1 diabetes mellitus. The two albumin molecules differed slightly in charge, non-enzymatic glycated albumin being more anionic at physiological pH compared with unmodified plasma albumin. Glycated albumin in plasma and urine was determined by a specific, sensitive and highly reproducible chromatographic procedure. In diabetic patients with normal urinary albumin excretion, the selectivity index was increased threefold compared with that of non-diabetic subjects (2p< 0.01). A significant correlation (r=0.53, 2p < 0.01) between haemoglobin A_1c and selectivity index was demonstrated in these patients, indicating a change in charge-dependent renal filtration could possibly be attributed to non-enzymatic glycation of components in the glomerular basement membrane and tubuli. Diabetic patients with increased albumin excretion rate had a significantly lower selectivity index compared with patients with normal albumin excretion (2p < 0.01). A significant negative correlation (r=0.85, 2p <0.001, exponential curve fit) was seen between urinary albumin excretion and selectivity index in the diabetic patients, indicating that the capability of differentiating between macromolecules of different charges is again lost with increasing urinary albumin excretion.In conclusion, the selectivity index is significantly increased in Type 1 diabetic patients with normal urinary albumin excretion, possibly due to non-enzymatic glycation of structural glomerular proteins. The selectivity index is again reduced with increasing urinary albumin excretion, possibly due to structural changes different from non-enzymatic glycation. This observation is in accordance with the hypothesis that loss of anionic charges due to reduced heparan sulphate content in glomerular basement membranes plays an important role in the early stages of diabetic renal disease.     

Glomerular hyperfiltration and urinary prostaglandins in type 1 diabetes mellitus

In order to determine whether glomerular hyperfiltration in diabetes is related to renal prostaglandin production we have studied the urinary excretion of PGE2, 6-keto-PGF1 alpha, and TXB2 in two sex, age and duration of diabetes matched groups of 9 and 10 Type 1 diabetic patients with either normal (mean 121, range 105-129 ml min-1 1.73 m-2) or supranormal glomerular filtration rate (154, 135-206 ml min-1 1.73 m-2). A group of 15 matched healthy volunteers served as control subjects. Urine was collected overnight for an uninterrupted period of at least 6 h. All studies in the patients were performed during insulin-induced sustained euglycaemia to prevent the confounding effect of variable degrees of blood glucose control on urinary prostaglandin excretion. Blood pressure was normal in all subjects. Urinary excretion of 6-keto-PGF1 alpha was significantly higher in the patients with glomerular hyperfiltration (median 17.1, range 4.5-33.6 ng h-1) than in those without (8.8, 1.5-13.8 ng h-1; p less than 0.05) or in normal control subjects (9.6, 5.2-15.5 ng h-1; p less than 0.05). No significant differences were found in the excretion rates of PGE2 and TXB2 between the three groups. Under conditions of controlled plasma glucose and insulin concentrations the urinary excretion of 6-keto-PGF1 alpha, the stable breakdown product of PGI2, a compound of endothelial, possibly glomerular, origin was elevated only in the diabetic patients with glomerular hyperfiltration.     

Urinary excretion of the carboxy terminal domain of type IV collagen is associated with kidney size and function in IDDM

We evaluated whether urinary excretion of the carboxy terminal domain (NC1) of Type IV collagen is associated with glomerular filtration rate and kidney size in Type I (insulin-dependent) diabetes mellitus (IDDM). Urinary excretion rate of NC1, glomerular filtration rate (GFR), and kidney size were measured in 16 men with Type I diabetes. Their mean age was 33.3 ± 6.1 years with a duration of diabetes of 14.9 ± 3.7 years (mean ± SD). The urinary excretion rate of NC1 was higher in the diabetic patients than in 18 healthy control subjects. Urinary excretion of NC1 was associated with both kidney size, parenchymal width, and GFR (r = 0.73, p = 0.001; r = 0.63, p = 0.009; r = 0.53, p = 0.04, respectively). The exact relationship between these factors and basement membrane turnover/synthesis remains to be elucidated.     

The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus

Summary The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non-diabetic rats. Glomerular prostaglandin E and 6-ketoprostaglandin F₁ production was significantly increased in glomeruli obtained from the diabetic rats. Inhibition of aldose reductase caused a reduction in the raised glomerular prostaglandin production, although this remained above that observed in the non-diabetic rats. Subsequent experiments were performed to determine whether the effects of the aldose reductase inhibitors could be explained by effects on glomerular filtration rate. It was found that ponalrestat, at a dose which markedly reduced urinary albumin excretion, did not significantly affect glomerular filtration rate in non-diabetic rats, rats with untreated streptozotocin-induced diabetes and rats with diabetes partially treated with low dose insulin. Glomerular sorbitol concentrations were significantly elevated in untreated diabetic rats as early as two weeks after the induction of diabetes. It is concluded that the administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion. The latter effect is not due to an effect on glomerular filtration rate. Increased polyol pathway activity may account in part for the increased glomerular prostaglandin production and urinary albumin excretion in early experimental diabetes.