尿液LAP和GGT联合检测对糖尿病早期肾损害的诊断价值

目的探讨尿亮氨酸氨基肽酶（LAP）和γ-谷氨酰基转移酶（GGT）筛查糖尿病早期肾损害的临床价值。方法采用速率法对糖尿病肾损害组和无肾损害组及正常对照组进行尿LAP、GGT及尿肌酐（Cr）水平检测,并用U/gCr的单位表示酶活性。结果糖尿病无肾损害组和肾损害组患者尿LAP和GGT活性明显高于正常对照组（P〈0.01）;糖尿病肾损害组高于糖尿病无肾损害组（P〈0.01）;且LAP和GGT呈正相关（r=0.59,P〈0.01）。结论尿LAP和GGT的联合检测对糖尿病患者早期肾损害具有诊断价值。     

4种尿微量蛋白联合检测对2型糖尿病肾病改变的临床诊断的应用评价

目的 进行4种尿液微量蛋白:尿转铁蛋白(UTRF)、尿免疫球蛋白G(UIgG)、尿微量清蛋白(UmALB)、尿α1-微球蛋白(Uα1-M)的联检,观察其在2型糖尿病(T2DM)肾病改变的变化,探讨其临床诊断价值方法采用速率散射比浊法测定UTRF、UIgG、Uα1-M、UmALB的浓度,分析其在T2DM肾病改变中的变化结...     

尿清蛋白检测性能评价及尿清蛋白/肌酐比值联合肾小球滤过率对2型糖尿病患者肾损伤的诊断价值

目的评价免疫透射比浊法检测尿清蛋白(Alb)的性能,探讨尿Alb/肌酐(Cr)比值(ACR)联合估算肾小球滤过率(e GFR)在2型糖尿病(T2DM)患者肾损伤评价中的诊断价值。方法对免疫透射比浊法检测尿Alb的精密度、正确度、分析测量范围(AMR)、检测限、参考区间进行验证,并分析其与免疫散射比浊法的相关性和偏差。选取220例T2DM住院患者,检测尿Alb、尿Cr、血Cr,计算ACR和e GFR并进行分析。结果尿Alb在11.11~298.76 mg/L范围内批内、批间不精密度均小于厂家声明的标准。正确度验证显示两种诊断系统尿Alb校准品测定结果符合验证要求;CAP室间质评物(U-A、U-B)、校准验证/线性评价物(LN20-B)结果符合CAP校准验证/线性评价误差界限所规定的标准,相对偏倚小于基于生物学变异设定质量规范中的适当允许偏倚(<16.4%)。AMR验证显示尿Alb在5.08~347.93 mg/L范围内线性良好。方法学比对显示透射比浊法与散射比浊法检测尿Alb结果相关性较好,平均绝对偏差为8.6 mg/L,平均相对偏差为14.52%,在医学决定水平处的预期偏差在可接受范围内。220例T2DM患者按照正常Alb、微量Alb、大量Alb尿分组,分别有10.9%、45.7%、66.7%的患者e GFR<60m L·min-1·1.73 m-2;在e GFR≥90 m L·min-1·1.73 m-2的患者中,15.7%有微量Alb尿,7.1%有大量Alb尿。结论免疫透射比浊法检测尿Alb的各项性能指标基本满足实验室要求,联合应用ACR和e GFR有助于评估T2DM患者肾脏损伤状况。     

Gene- and cell-based therapeutics for type I diabetes mellitus

Type 1 diabetes mellitus, an autoimmune disorder is an attractive candidate for gene and cell-based therapy. From the use of gene-engineered immune cells to induce hyporesponsiveness to autoantigens to islet and beta cell surrogate transplants expressing immunoregulatory genes to provide a local pocket of immune privilege, these strategies have demonstrated proof of concept to the point where translational studies can be initiated. Nonetheless, along with the proof of concept, a number of important issues have been raised by the choice of vector and expression system as well as the point of intervention; prophylactic or therapeutic. An assessment of the current state of the science and potential leads to the conclusion that some strategies are ready for safety trials while others require varying degrees of technical and conceptual refinement.     

血清胱抑素C检测在评价2型糖尿病早期肾功能损害中的应用

目的探讨血清胱抑素C（CysC）水平测定在2型糖尿病患者不同肾损害期中的临床诊断价值。方法采用乳胶颗粒增强免疫透射比浊法（PETIA）测定2型糖尿病患者150例血清CysC水平,同时测定血清肌酐（SCr）、尿素氮（Bun）、β2-微球蛋白（β2-MG）及晨尿微量清蛋白,采用受试者工作特征曲线（ROC）评价CysC的诊断效能。结果2型糖尿病组血清CysC水平明显高于健康对照组（P〈0．01）,其中无糖尿病肾病（无DN）组、Ⅲ期DN组以及Ⅳ、Ⅴ期DN组间血清CysC水平比较差异有统计学意义（P〈0．01）。在无DN组中,血清CysC、β2-MG、SCr、Bun四项指标的异常检出率无显著差异（P〉0．05）,但在Ⅲ期DN组中,CysC、β2-MG的异常检出率明显高于SCr和Bun（P〈0．01）。以尿微量清蛋白为标准,2型糖尿病患者中DN的诊断敏感性和特异性,血CysC（以1．22mg／L为界值）分别为72．1％、88．6％,β2-MG（以2．82mg／L为界值）分别为79．0％、92．3％,SCr（以101μmol／L为界值）分别为46．2％、93．5％,Bun（以6．19mmol／L为界值）分别为41．7％、84．3％。CysC、β2-MG诊断DN的敏感性显著高于SCr和Bun（P〈0．01）,4项指标诊断DN的特异性差异无统计学意义（P〉0．05）。CysC、β2-MG、SCr、Bun的ROC分别为0．781、0．812、0．645、0．619。结论血清Cys C是一个灵敏、准确、可靠的反映肾小球滤过功能的指标,有助于2型糖尿病肾病的早期诊断。     

血、尿β痕迹蛋白检测对2型糖尿病肾损伤早期诊断价值研究

目的探讨血、尿β痕迹蛋白(βTP)检测在2型糖尿病肾损伤中的诊断价值。方法明确诊断为2型糖尿病患者178例,按照尿Alb/Cr比值将其分为三组:Alb/Cr正常组60例,微量白蛋白尿组65例,大量白蛋白尿组53例,另设健康对照组80名。采用胶乳增强散射免疫比浊法原理检测血、尿βTP,比较各组患者血、尿βTP水平,并与Scr、eGFR以及实验及临床相关指标进行相关性分析。结果尿Alb/Cr正常的2型糖尿病患者血清βTP为(0.70±0.36)mg/dl,较健康对照组[(0.59±0.12)mg/dl]显著升高(P<0.01)。微量白蛋白尿组血清βTP(0.82±0.30)mg/dl,较Alb/Cr正常组显著升高(P<0.05);大量白蛋白尿组血清βTP(1.79±1.19)mg/dl,与其他两组比较显著升高(P<0.01);三组2型糖尿病患者血清βTP阳性率分别为28.3%、60.0%和87.8%;尿液βTP/Cr阳性率分别为20%、84.6%和90.6%。相关分析结果表明,血清βTP与SC呈显著正相关,r为0.705 0(P<0.01),eGFR值与血β-TP呈显著负相关(r=-0.805 1,P<0.01)。尿βTP与Scr、HbA1c、收缩压、病程呈正相关(r分别为0.387 9、0.240 2、0.164 3、0.241 5,均P<0.05)。结论血清βTP对2型糖尿病患者早期肾损伤具有重要的诊断价值,可以早期反映肾小球滤过功能,而尿βTP/Cr可以作为评价2型糖尿病患者肾小管损伤的有效指标。     

Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus.

Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32, micromol.kg-1.min-1, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.     

糖尿病自身抗体联合检测在糖尿病分型中的应用价值研究

目的探讨糖尿病自身抗体联合检测在糖尿病分型中的应用价值,为正确分型糖尿病提供理论依据。方法选择我院内分泌科收治的126例糖尿病患者,其中1型糖尿病组51例,2型糖尿病组75例,同时选择健康对照组60例,采用免疫印迹试剂法检测胰岛细胞抗体（ICA）、胰岛素自身抗体（IAA）和谷氨酸脱羧酶抗体（GADA）表达情况,计算阳性率,并对结果进行比较分析。结果 ICA、IAA和GADA在1型糖尿病患者中的阳性率分别为35.3%、31.4%和60.8%,显著高于2型糖尿病患者的1.3%、1.3%、2.7%及对照组的1.3%、0.0%、0.0%,均有显著性差异（P〈0.05）。ICA/IAA/GADA、GADA/ICA、GADA/IAA三种联合检测组合对1型糖尿病诊断的敏感性分别为92.2%、84.3%和82.4%,均显著高于单一抗体检测,均有显著性差异（P〈0.05）。结论检测血清ICA、IAA和GADA能够为正确鉴别1型糖尿病和2型糖尿病提供重要依据,联合检测能够提高诊断阳性率,避免漏诊,值得临床推广和普及。     

应用原核细胞表达法体外制备基因重组胰岛素降解酶的活性

目的:利用原核细胞表达法体外制备基因重组胰岛素降解酶,并分析其活性。方法:实验于2004-05/11在北京老年医学研究所神经生物研究室完成。将编码大鼠胰岛素降解酶的cDNA插入质粒pGEX-4T-1并转化大肠杆菌BL21,使其表达谷胱甘肽巯基转移酶为标签的融合蛋白质。凝血酶定点分解融合蛋白,用谷胱甘肽-琼脂糖4B亲合层析方法纯化基因重组胰岛素降解酶。重组胰岛素降解酶的活性应用高压液相色谱进行判断。结果:①胰岛素降解酶cDNA编码区片段的亚克隆:重组质粒亚克隆的cDNA片段为3060bp,编码1019个氨基酸。②胰岛素降解酶在原核细胞的表达与纯化:重组质粒pGEX-rIDE在原核细胞中表达为可溶性组分,培养菌液可收获目的基因重组酶约0.5mg/L,纯化的胰岛素降解酶在SDS-PAGE上表现为单一条带,其表观相对分子质量为110000,与野生型酶相同。③基因重组蛋白质对胰岛素的降解作用:牛胰岛素与基因重组蛋白质的洗脱峰分别出现在34.5和38.3min,将纯化的重组蛋白与胰岛素在37℃下共同孵育后,胰岛素含量明显减少。孵育的最初20min质量变化明显,其峰面积值减少了约50%,但其余时间降解不明显。该蛋白质对14-3-3蛋白的两个亚型没有降解作用。结论:基因重组rIDE具有天然酶的活性,但该活性在孵育20min后胰岛素降解延缓,可能是胰岛素的降解产物反馈抑制了rIDE活性,与酶的自身调节有关。本实验制备了具有生物学活性的基因重组型大鼠胰岛素降解酶,为进一步制备抗胰岛素降解酶单克隆抗体以及探讨胰岛素降解酶与2型糖尿病发生之间的关系打下了基础。     

Acarbose and insulin therapy in type I diabetes mellitus

In this paper relevant studies are summarized regarding the use of acarbose as an adjunct to insulin in the treatment of type I diabetes. It is concluded that this approach may contribute to a reduction of postprandial blood glucose excursions and a smoothening of daily blood glucose profiles, an improvement of metabolic control as expressed by glycosylate haemoglobin values and a reduction of insulin requirements. Long-term studies are, however, necessary before one can conclude that addition of acarbose to the therapeutic regimen in type I diabetic subjects is of longstanding value.     

2型糖尿病风险评估工具的研究进展

糖尿病是一种慢性、终身性疾病,其中2型糖尿病占90% [1].2型糖尿病患病率高,并发症发生率高,会造成组织器官损害,具有致残、致死性,危害严重.     

2型糖尿病患者超敏C反应蛋白和血脂检测的应用研究

目的探讨2型糖尿病患者血清超敏C反应蛋白(hsCRP)与血脂的关系及其临床应用。方法用HITACHI7060C全自动生化分析仪检测49例2型糖尿病患者和53例健康体检者血清hsCRP、TC、TG、、HDLC、LDLC、ApoA1、ApoB。结果2型糖尿病组患者血清hsCRP、TC、TG、LDLC、ApoB均比健康对照组高,差异有统计学意义(其中hsCRP和ApoBP<0.01,其他P<0.05);HDLC低于健康对照组,差异有统计学意义(P<0.05);两组ApoA1比较无统计学意义。同时hsCRP浓度与TG、ApoB浓度呈正相关(r分别0.2159、0.1954,P<0.05);hsCRP浓度与HDLC浓度呈负相关(r为0.2705,P<0.01)。结论hsCRP作为一个炎症因子,在预测糖尿病并发心血管疾病中具有重要的临床意义;2型糖尿病患者常伴有血脂紊乱,提示患动脉粥样硬化的危险性增大。     

Extended major histocompatibility complex haplotypes in type I diabetes mellitus.

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.     

血清髓鞘碱性蛋白对2型糖尿病性周围神经病变的诊断意义

目的研究血清髓鞘碱性蛋白( MBP)在诊断 2型糖尿病周围神经病变中的价值.方法对 74例 2型糖尿病患者(其中周围神经病变组 38例、无神经病变组 36例)和 50例正常人测定血清髓鞘碱性蛋白( MBP),结合肌电图检查作对照.周围神经病变组给予葛根素加用甲钴胺联合治疗,观察神经传导速度( NCV)和 MBP的变化.结果 2型糖尿病有周围神经病变组( A组)、无神经病变组( B组)和正常人组( C组),血清 MBP分别为 (5.70± 2.50)μ g/L 、(1.71± 0.50)μ g/L及( 1.52± 0.21)μ g/L , A组与另 2组比较均有显著差异, p<0.001,而 B组与 C组比较无显著差异; A组经葛根素加用甲钴胺联合治疗, NCV明显好转, MBP明显下降,治疗前后有显著差异 p<0.01, NCV和 MBP的相关分析发现,它们显著负相关. 2型糖尿病神经病变肌电图阳性率 100%与 MBP阳性率 94.7% (36/38)比较无显著差异.结论血清 MBP测定可作为糖尿病周围神经病变的诊断和随访指标之一.     

Effect of exercise on urinary N-acetyl-beta-D-glucosaminidase activity and albumin excretion in children with type I diabetes mellitus

Urinary N-acetyl-beta-D-glucosaminidase (NAG), a proximal tubule lysosomal enzyme, has been used as an indicator of subtle renal injury. Since it has been positively and significantly correlated with hemoglobin A1c and microalbuminuria, it has been suggested that this enzyme may also reflect metabolic control. Albumin excretion is exacerbated in adult diabetic individuals during exercise; such exercise-induced albuminuria may be a forerunner of diabetic nephropathy. Metabolic control, degree of exertion, and duration of diabetes have been suggested to influence this increase in albuminuria during exercise. Studies of children are few and have produced inconsistent results. Thus we studied 28 insulin-dependent diabetic children ranging in age from 5 yr to 16 yr and 27 age-matched controls using treadmill exercise; two exercise periods consisting of (1) graded increases in speed and grade at 3-min intervals until exhaustion and (2) a constant speed and grade necessary to produce 2/3-3/4 maximal heart rate for 30 min were performed. Capillary blood glucose, urinary NAG/creatinine (cr) ratios (UNAG/Ucr) and urinary albumin/creatinine ratio (Ualb/Ucr) were measured before and after each exercise period; hemoglobin A1c was also measured. The latter averaged 11.8 +/- 0.6% (mean +/- SEM); contrary to previous studies, this was not correlated with pre- or postexercise UNAG/Ucr. During both exercise periods, blood glucose dropped 271 +/- 19 mg/dl to 213 +/- 21 mg/dl (period 1) and 230 +/- 22 mg/dl to 157 +/- 21 mg/dl (period 2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative assessment of dietary adherence in patients with insulin-dependent diabetes mellitus

Research on the education of diabetic patients in diet management suffers from lack of an adequate method for describing patients' dietary behavior. In this report, a method is proposed for the quantitative assessment of dietary adherence in patients with IDDM. The method relies on comparisons between individualized diet plans and actual consumption as reflected by 24-h diet recalls. Data are presented that suggest this method has reliability and validity. In a sample of 97 patients with IDDM, nearly two-thirds adhered to the number and timing of planned feedings, while only about 10% of patients adhered to planned exchanges, 90% of the time. The average patient added or deleted one exchange for every four exchanges in the diet plan.     

Quantitative assessment of power Doppler mapping in the detection of renal allograft complications.

PURPOSE: We evaluated the usefulness of power Doppler (PD) imaging with a quantitative parameter in the identification of renal transplant complications. METHODS: One hundred eight transplanted kidneys were subjected to PD examinations. The blood flow area ratio (BFAR), defined as the percentage of the area of color pixels within a given cross-sectional area placed over a region of a transplanted kidney, was measured using built-in color histogram software and used as a quantitative parameter for evaluating the status of allograft blood perfusion. The mean BFARs in the normal, acute rejection (AR), acute tubular necrosis (ATN), chronic rejection (CR), and cytomegalovirus infection (CMV) groups were compared. RESULTS: The BFAR in the normal group tended to decrease gradually with the time interval since transplantation, but the mean value, 0.68+/-0.08, was significantly higher than that in the complication groups: AR, 0.43+/-0.18; ATN, 0.43+/-0.14; CR, 0.15+/-0.14; and CMV, 0.36+/-0.10 (p < 0.01 for all). When a BFAR of 0.60 or greater was used as the diagnostic criterion for normal allografts, a sensitivity, specificity, and accuracy of more than 90% could be achieved in the diagnosis of complications. However, owing to overlapping BFARs among the complication groups, the BFAR alone had a limited ability to differentiate the types of complications. CONCLUSIONS: Although PD imaging has some limitations in identifying the nature of renal allograft complications, the use of the quantitative parameter BFAR in the PD assessment of renal allografts may be useful in detecting complications. Further studies are needed to explore the BFAR's clinical value.     

Taste impairment and related factors in type I diabetes mellitus

To study taste in type I (insulin-dependent) diabetes mellitus, 57 consecutive diabetic outpatients (mean +/- SE duration of diabetes 11.4 +/- 0.4 yr) and 38 control subjects were screened for taste disorders with electrogustometry and chemical gustometry. Both groups were comparable for all subject characteristics except body mass index, which was higher in the diabetic group (P less than .05). A taste impairment was found in the diabetic group relative to the control group with electrogustometry (mean threshold 184.3 +/- 15.8 vs. 58.7 +/- 9.2 microA; P less than .001) and chemical gustometry (mean score 13.2 +/- 0.7 vs. 17.1 +/- 0.8; P less than .001). Hypogeusia was found among 73% of the diabetic patients versus 16% of the control subjects (P less than .001). The four primary tastes were involved in taste impairment. With multivariate analysis, taste disorders were related to diabetic status and tobacco and alcohol consumption. In the diabetic group, taste impairment was significantly associated with complications and duration of disease. With multivariate analysis, peripheral neuropathy had the strongest association with taste disorders. These results suggest that taste is impaired during the course of type I diabetes mellitus and that taste impairment could be a complication of the disease. A mechanism of the neuropathic type could be involved.