尿液肾功能指标和血清半胱氨酸蛋白酶抑制剂 Ｃ 对早期糖尿病肾病的 诊断价值及其风险评估模型的建立

摘要：目的 探讨尿液肾功能指标和血清半胱氨酸蛋白酶抑制剂 Ｃ（ＣｙｓＣ）对早期糖尿病肾病（ＤＮ）的诊断价值，同时构建早 期 ＤＮ 风险评估列线图模型。 方法 回顾性分析本院 ２０１９ 年 １ 月至 ２０２１ 年 １２ 月收治的 ８７３ 例 ２ 型糖尿病（Ｔ２ＤＭ）患者，根 据尿微量白蛋白／ 肌酐比值（ｕｍＡＣＲ）分为 Ｔ２ＤＭ 组（ｎ ＝ ３８７）、早期 ＤＮ（ＤＮ１）组（ｎ ＝ ３１３）和临床 ＤＮ（ＤＮ２）组（ ｎ ＝ １７３），比较 各组人群临床资料以及肾功能指标，并采用 ＲＯＣ 曲线分析各指标单独和联合诊断效能，用 Ｒ 软件绘制相关分析热图，多因素 Ｌｏｇｉｓｔｉｃ 回归分析 ＤＮ 发生的独立危险因素，建立 ＤＮ 诊断模型并采用 Ｂｏｏｔｓｔｒａｐ 法验证。 结果 血清 ＣｙｓＣ、ｅＧＦＲ、尿 α１ －微球 蛋白（ｕα１ ?ＭＧ）、尿 β２ 微球蛋白（ｕβ２ ?ＭＧ）、尿免疫球蛋白 Ｇ（ｕＩｇＧ）、尿转铁蛋白（ｕＴｒＦ）和尿微量清蛋白（ ｕｍＡｌｂ）水平：ＤＮ２ 组 ＞ＤＮ１ 组＞Ｔ２ＤＭ 组，差异均有统计学意义（Ｐ 均＜０．０５）；多指标联合诊断的 ＲＯＣ 曲线下面积（ＡＵＣ ＲＯＣ ）为 ０．９０４，敏感性和特异 性分别为 ７５．４％和 ９５．１％，均高于各指标单独检测效能。 ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 与 ｕｍＡＣＲ 呈正相关，与 ｅＧＦＲ 呈 负相关（Ｐ 均＜０．００１）。 多因素 Ｌｏｇｉｓｔｉｃ 回归分析结果显示，年龄、ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 是 ＤＮ 的独立危险因素 （Ｐ 均＜０．０５），列线图评估 ＤＮ 风险的一致性指数（Ｃ?ｉｎｄｅｘ）为 ０．９１９，区分度良好；校准图显示预测风险发生率与实际风险发生 率有良好的一致性。 结论 ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 联合对早期 ＤＮ 具有较高诊断价值，基于以上指标所建立的 个体化预测 ＤＮ 发生风险的列线图模型具有良好的准确度与区分度，对 Ｔ２ＤＭ 并发 ＤＮ 高风险人群的早期诊断和干预提供了 可靠的依据。     

急性心肌梗塞、急性脑梗塞及糖尿病患者红细胞变形能力的研究

目的：探讨急性心肌梗塞（ＡＭＩ）、急性脑梗塞（ＡＣＩ）及糖尿病（ＤＭ）患者的发病与血液流变学中红细胞变形能力（ＲＣＤ）的变化关系。方法：采用德国ＦＭ４红细胞过滤仪，检测ＡＭＩ、ＡＣＩ及ＤＭ患者的ＲＣＤ。结果：ＡＭＩ、ＡＣＩ及ＤＭ３组患者的ＲＣＤ的最小余量明显高于对照组（Ｐ均＜０．０１），斜明显低于对照组。ＡＭＩ发病２４小时内的ＲＣＤ最小余量明显高于治疗２周后的ＲＣＤ的最小余量（Ｐ＜０．０１）。ＡＭＩ组ＲＣＤ最小余量与５．７５ｓ－１切变率的粘度呈正相关（ｒ＝０．３５０，Ｐ＜０．０５），与２３０ｓ－１切变率的粘度呈明显正相关（ｒ＝０．５６２，Ｐ＜０．００１）。结论：直接检测ＲＣＤ的变化，对估测活动期心脑血管病及糖尿病微血管病变的轻重及治疗效果有一定的意义。     

急性脑血管病与植物神经功能障碍

分析２３０例急性脑血管病（ＡｃｕｔｅＣｅｒｅｂｒａｌＶａｓｃｕｌａｒｄｉｓｅａｓｅ，ＡＶＣＤ）合并植物神经功能障碍（Ｖｅｇｅｔａｔｉｖｅｎｅｒｖｅｆｕｎｃｔｉｏｎａｌｄｉｓｏｒｄｅｒｓ，ＶＮＦＤ）患者，发病率为２２．３％，其中脑梗塞１２４例，占５３．９％，脑出血７５例，占３２．６％，蛛网膜下腔出血３１例，占１３．５％，以梗塞面积大，出血量多者发生率较高，ＶＮＦＤ依次为：心血管功能障碍，消化道功能紊     

局部温热并热敏性阿霉素微脂粒治疗乳腺癌

采用局部温热并热敏性阿霉素微脂粒（ＨＴ－Ｔｓ－ＬｉＰ－ＡＤＭ）治疗乳腺癌４０例，以环磷酰胺、阿霉素、５－氟尿嘧啶（ＣＭ）联合方案治疗乳腺癌２０例作对照。结果表明，一疗程后，ＨＴ－Ｔｓ－ＬｉＰＡＤＭ组ＣＲ＋ＰＲ３４例，ＭＲ４例，ＳＤ２例，总有效率为８５％，未见病变进展。ＣＡＦ组ＣＲ＋ＰＲ８例．ＭＲ６例，ＳＤ４例，总有效率４０％，２例病变进展。两组比较ＨＴ－Ｔｓ－ＬｉＰ－ＡＤＭ组疗效明显提高（Ｐ＜０．０１），其毒性反应，恶心呕吐、心脏毒性及骨髓抑制明显减少。     

胰岛素依赖型糖尿病患者外周T淋巴细胞亚群及血清SIL─2R变化

检测胰岛素依赖型糖尿病（ＩＤＤＭ）患者１４例、非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者２３例和正常对照组３０例血清可溶性白介素２受体（ＳＩＬ─２Ｒ）水平以及Ｔ淋巴细胞亚群的变化，结果发现，ＩＤＤＭ患者ＳＩＬ─２Ｒ水平显著低于正常对照组和ＮＩＤＤＭ组（Ｐ＜０．０１；Ｐ＜０．０５）。ＣＤ８显著低于正常对照组和ＮＩＤＤＭ组（Ｐ均＜０．０１），ＣＤ４／ＣＤ８比值明显升高，与正常对照组和ＮＩＤＤＭ组比较有显著性差异（Ｐ＜０．０１）。ＩＤＤＭ患者ＳＩＬ─２Ｒ水平与糖化血红蛋白和空腹血糖均无明显相关，但与空腹Ｃ肽呈显著性正相关（ｒ＝０．６８３，Ｐ＜０．０１）。结果表明，病程小于１年ＩＤＤＭ患者血清ＳＩＬ─２Ｒ以及淋巴细胞亚群异常改变导致免疫功能紊乱，血清ＳＩＬ─２Ｒ可作为衡量ＩＤＤＭ免疫异常指标之一，并对判断病情及胰岛功能、指导治疗都具有一定临床意义。     

胰岛素依赖型糖尿病患者外周T淋巴细胞亚群及血清SIL—2R变化

检测胰岛素依赖型糖尿病（ＩＤＤＭ）患者１４例、非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者２３例和正常对照组３０例血清可溶性白介素２受体（ＳＩＬ－２Ｒ）水平以及Ｔ淋巴细胞亚群的变化，结果发现，ＩＤＤＭ患者ＳＩＬ－２Ｒ水平显著低于正常对照组和ＮＩＤＤＭ组（Ｐ〈０．０１；Ｐ〈０．０５）。ＣＤ８显著低于正常对照组和ＮＩＤＤＭ组（Ｐ均〈０．０１），ＣＤ４／ＣＤ８比值明显升高，与正常对照组和ＮＩＤＤＭ组比较有显著     

中枢神经系统疾病患者脑脊液中的IL—2R

本文采用双抗体夹心酶标法检测了１０２例中枢神经系统疾病病人ＣＳＦ及３５例正常人ＣＳＦ中ｓＩＬ－２Ｒ水平。结果显示：结核性脑膜炎组（ＴＢＭＧ）、病毒性脑炎（ＤＭＧ）脱髓鞘性疾病组（ＤＭＤＧ）ｓＩＬ－２Ｒ水平明显高于其它神经系统疾病（ＯＮＤ）和正常人（ＮＣ）组（Ｐ〈０．０１）。ＴＢＭＧ进展期与恢复期比较，ｓＩＬ－２Ｒ水平有非常显著差异（Ｐ〈０．０１）。缓解期ＶＭＧ、ＤＭＤＧ的ｓＩＬ－２Ｒ水平与进展期比     

非胰岛素依赖型糖尿病自主神经病变对尿白蛋白排泄率的影响

目的：探讨糖尿自主神经病变与糖尿病肾病之间的关系。方法：将４６例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者按有无自主神经病分成两组，分别测定尿白蛋白排泄率（ＵＡＥＲ）。结果：伴自主神经病变组（ＡＮ组）夜间ＵＡＥＲ明显高于无自主神经病变组（无ＡＮ组）且与卧立位血压差和自主神经计人呈显著正相关，结论：自主神经病变使ＮＩＤＤＭ患者夜间ＵＡＥＲ增加，促进糖尿病肾病的发展。     

正常血压非胰岛素依赖型糖尿病病人血压昼夜节律与尿白蛋白排泄率的关系

目的：了解偶测血压正常的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人血压水平及其昼夜节律与尿白蛋白排泄率（ＡＥＲ）的关系。方法：将５５例临床无高血压、无糖尿病肾病的ＮＩＤＤＭ病人按ＡＥＲ水平分为微量白蛋白尿组（ＭＡ组）和正常白蛋白尿组（ＮＡ组），同步测定２４小时动态血压和ＡＥＲ，分析比较其关系。结果：ＭＡ组偶测血压、白天血压、２４小时平均血压与ＮＡ组比较无显著差异，夜间血压和血压昼夜节律异常的发生率则明显高于ＮＡ组，而无明显血压昼夜节律者ＡＥＲ水平和微量白蛋白尿的发生率明显高于有昼夜节律者。结论：在偶测血压正常的ＮＩＤＤＭ病人，动态血压监测较偶测血压更易发现夜间血压异常，血压昼夜节律改变与ＡＥＲ的关系较２４小时平均血压更为密切。     

冠心病,糖尿病和系统性红斑狼疮患者的可溶性血管内皮细？…

目的：检测冠心病（ＣＨＤ）、糖尿病（ＤＭ）、系统性红斑狼疮（ＳＬＥ）患血浆中的可溶性血管内皮细胞蛋白Ｃ受体（ｓＥＰＣＲ）水平,以探讨ｓＥＰＣＲ在不同疾病患血浆中表达水平及其临床意义。方法采用酶联免疫双抗体夹心法检测３４例ＣＨＤ、４２例ＤＭ、６３例ＳＬＥ患及２０名正常人（ＮＣ）血浆中的ｓＥＰＣＲ水平。结果ｓＰＥＣＲ在ＤＭ患血浆中的表达水平明显高于正常对照血浆（Ｐ〈０．０５）;ＳＬＥ合并血栓及     

Heart rate variability in diabetes patients

Diabetes mellitus can cause cardiovascular autonomic neuropathy and is associated with increased cardiovascular deaths. We investigated cardiovascular autonomic neuropathy in diabetics and healthy controls by analysis of heart rate variability. Thirty-one diabetics and 30 age- and sex-matched controls were included. In the time domain we measured the mean R - R interval (NN), the standard deviation of the R - R interval index (SDNN), the standard deviation of the 5-min R - R interval mean (SDANN), the root mean square of successive R - R interval differences (RMSSD) and the percentage of beats with a consecutive R - R interval difference > 50 ms (pNN50). In the frequency domain we measured high-frequency power (HF), low-frequency power (LF) and the LF/HF ratio. Diabetes patients had lower values for time-domain and frequency-domain parameters than controls. Most heart rate variability parameters were lower in diabetes patients with chronic complications than in those without chronic complications.     

定量组织速度成像评价自主神经病变对Ⅰ型糖尿病患者左室功能的影响

目的应用定量组织速度成像(QTVI)技术评价自主神经病变对Ⅰ型糖尿病患者左室舒张功能的影响。方法应用QTVI软件测定糖尿病组(60例)及正常组(30例)二尖瓣环水平后间隔、侧壁、前壁、下壁、后壁、前间隔6个部位的收缩期(Vs)、舒张早期(Ve)、舒张晚期(Va)室壁运动峰值速度,比较两组间各参数的差异性。根据心率变异分析(HRV)将糖尿病组进一步分为心自主神经功能正常组(CAN-)(22例)及心自主神经功能异常组(CAN )(38例),比较两组间Ve/Va<1的检出率是否有统计学意义。结果糖尿病组Ve低于对照组,二者有统计学意义(P<0.05);Ve/Va明显低于正常组(P<0.001),二者有统计学意义。在CAN-组中的Ve/Va<1的节段数明显少于CAN 组(χ2=82.8,P<0.001),二者有显著性差异。结论QTVI能够准确定量评价糖尿病自主神经病变患者的左室舒张功能,并能敏感反映自主神经损害对左室舒张功能的影响,为临床选择合理的治疗措施及对疗效的评判提供了定量的指标。     

Autonomic neuropathy in diabetes mellitus, chronic renal failure and liver cirrhosis

Chronic diseases (diabetes mellitus, end stage renal failure on hemodialysis, post-hepatitic liver cirrhosis) caused autonomic neuropathy in 34 of 65 cases. The frequency of autonomic neuropathy was 14 of 30 diabetics (typ I and typ II), twelve of 19 patients on dialysis, and eight of 16 non-alcoholic liver cirrhotics. We did not find a correlation between the tests of the cardiovascular and of the gastrointestinal system. The distribution of the neuropathic changes was undependent of the underlying disorder. Using appropriate tests, alterations of the autonomic functions can be discovered frequently even in asymptomatic patients. At least two pathological test results are necessary to reach a significant difference between patients and healthy controls. This indicates that the diagnosis of autonomic neuropathy should rely on two or more pathological test results. The evidence of autonomic neuropathy identifies a population of high risk patients.     

皮肤交感电位在糖尿病自主神经病亚临床病变的诊断价值

目的探讨皮肤交感电位(SSP)与糖尿病自主神经病的相关性,为糖尿病自主神经病的早期诊断提供客观依据。方法对65例糖尿病合并自主神经病患者,60例糖尿病患者及40例健康人的四肢进行SSP测定,对3组SSP各潜伏期及波幅的均值进行比较分析。结果糖尿病非自主神经病组的SSP起始潜伏期、N波、P波潜伏期与正常对照组比较差异均有统计学意义(均P<0.01)、N波波幅,P波波幅差异无统计学意义(P>0.05)。糖尿病自主神经病组中,35例神经传导速度显示为神经纤维脱髓改变,为上肢及下肢SSP潜伏期显著延长,以下肢延长为著,在下肢延长的同时其波幅亦有降低,在神经传导速度显示的神经轴索损害的30例患者中,双下肢的SSP均未引出波形,而上肢SSP潜伏期明显延长,波幅降低。2组比较差异有统计学意义(P<0.01)。健康对照组全部引出SSP。结论SSP为糖尿病自主神经病的早期诊断提供了新的方法和诊断依据,可发现糖尿病自主神经病亚临床病变。     

蹲踞试验对糖尿病心血管自主神经病变的诊断价值——附66例分析

目的：评价蹲踞试验对糖尿病心血管自主神经病变的诊断价值。方法：对６６例２型糖尿病患者和４４名正常对照组同期进行蹲踞经典心电图心血管自主神经功能测定。结果 与对照组同年龄比较，糖尿病踞副交感神经功能比值（ＳｑＴｖ）明显升高，蹲踞交感神经功能比值（ＳｑＴａ）显著降低；与对照组和正常清蛋白尿患者比较，伴清蛋水者，尤其是大量清蛋白尿者。ＳｑＴｖ明显升高，ＳｑＴｓ明显降ｑＴｖ和ＳｑＴｓ和经典心血管自主神经功     

Progression of diabetic autonomic neuropathy over a decade in insulin-dependent diabetics

The prognosis for diabetics with autonomic neuropathy is little known. We therefore studied the progress of young insulin-dependent diabetics, first identified as having abnormal autonomic function 10-15 years ago. We have shown that the mortality of diabetics with symptomatic autonomic neuropathy is increased, but is less than previously reported. Mortality in asymptomatic diabetics with an isolated abnormality in autonomic function tests is not increased. The heart rate variability declines at 1.02 +/- 0.47 (SD) per annum in diabetics with an initially normal heart rate variability. While symptoms of autonomic neuropathy do not usually remit even over a decade, they do not commonly progress. Three groups of young insulin-dependent diabetics had heart rate variability tested between 1972 and 1977 and have been reviewed 10-15 years later. Group A (n = 49) had symptomatic autonomic neuropathy and an abnormal heart rate variability (less than 12), Group B (n = 24) were asymptomatic yet had an abnormal heart rate variability and Group C (n = 38) were asymptomatic and had a normal heart rate variability (16-26). The 10-year survival in Group A (73.4 per cent) was less (P less than 0.05) than in Groups B (91.7 per cent) or C (89.5 per cent) which did not differ from each other. The 18 Group A deaths were due predominantly to renal failure (n = 4), myocardial infarction in patients with nephropathy (n = 3) and sudden unexpected death (n = 3). The chief symptoms of autonomic neuropathy--diarrhoea, postural hypotension and gustatory sweating, were very persistent but did not necessarily deteriorate or become disabling in the majority of patients. The development of autonomic symptoms in asymptomatic patients with abnormal heart rate variability was uncommon over a decade.     

The influence of autonomic neuropathy on mortality in insulin-dependent diabetes

Five-year survival was investigated in 506 randomly selected patients with insulin-dependent diabetes mellitus screened for autonomic neuropathy with a series of cardiac autonomic function tests. Of the 484 diabetics traced, 44 (9 per cent) had died. The cumulative 5-year mortality rate was increased more than five-fold in those with autonomic neuropathy: 27 per cent vs. 5 per cent in those with normal autonomic function. Discriminant analysis of survivors and non-survivors showed that autonomic neuropathy was the most important independent predictor of death. Among those who died, autonomic neuropathy was associated with an increased frequency of retinopathy and peripheral neuropathy and a slightly lower frequency of macrovascular disease. Autonomic neuropathy was associated with an increased mortality rate from renal failure, but not from any other causes.     

Sonographic study of postprandial gallbladder emptying and common bile duct changes in patients with diabetes or cholelithiasis

The aim of our study was to evaluate postprandial emptying of the gallbladder and common bile duct (CBD) in 20 patients with gallstones and in 20 diabetic patients with or without autonomic neuropathy. Gallbladder fasting volume was significantly increased in patients with multiple stones. Diabetics with autonomic neuropathy showed a decreased gallbladder emptying rate. CBD size did not show any significant change in all groups examined.     

Quantitative evaluation of diabetic autonomic neuropathy by using heart rate variations--determination of the normal range for the diagnosis of autonomic neuropathy

Heart rate (HR) variations--in supine resting position, during deep breathing and on standing--were measured in 162 healthy subjects and 168 diabetics by use of an instantaneous-HR-change continuous recorder. As indices of HR variations, the standard deviation of the HR at rest (SD of HR), the mean difference between maximal and minimal HR during deep breathing (delta I-E) and the HR increase on standing (delta HR) were determined. In healthy subjects, the values for each test declined with age and the log-transformed data fitted the linear regression. The 90% confidence limits were calculated for the normal range and the values below normal range were defined as abnormal. In diabetics, the incidence of abnormal response were 19% in the SD of HR, 38% in the delta I-E and 22% in the delta HR. The delta I-E was the most sensitive index for the autonomic neuropathy. The delta HR was considered to be able to detect the different mechanisms of neural reflexes because of the poor correlation between the delta HR and the respiratory HR variations. The present studies suggested that delta I-E and delta HR should be measured at the same time to evaluate the autonomic neuropathy.     

The pupillary light reflex in borderline diabetics

Computerized IR videopupilography, using an open-loop photic stimulator, was used to compare the reflexes of borderline diabetics with overt non-insulin-dependent diabetics and with age- and sex-matched non-diabetic healthy controls. The patients were all male, aged 41-59 years. Overt non-insulin-dependent diabetics in their 40s had a smaller pupillary area and pupillary diameter prior to photic stimulus compared with borderline diabetics and healthy controls. Overt non-insulin-dependent diabetics in their 50s had a lower pupillary area and pupillary diameter prior to photic stimulus, maximum velocity and acceleration of constriction and maximum velocity of dilation than did borderline diabetics or controls. The only abnormality observed among borderline diabetics compared to controls was a smaller amplitude of constriction in response to light in patients in their 50s. Amplitude of constriction in response to light and velocity of constriction measurements of borderline diabetics, however, were considerably more frequently abnormal than were those of controls. The frequency of abnormal pupillary diameter prior to photic stimulus, maximum velocity of dilation and acceleration of constriction was higher in overt non-insulin-dependent diabetics than in borderline diabetics. The results indicate that borderline diabetics have autonomic neuropathy before the disease becomes overt. The importance of the pupillary light reflex examination is discussed.