胰岛细胞抗体对糖尿病病因分型的临床意义

本采用免疫酶标（ＡＢＣ）法对２３例ＩＤＤＭ患,８８例ＮＩＤＤＭ患进行了ＩＣＡ检测,结果ＩＤＤＭ组阳性１０例（４３．４％）,ＮＩＤＤＭ组阳性８例（９．０９％）,两组比较有高度显性差异。ＮＩＤＤＭ组的８例ＩＣＡ阳性,实质是缓慢进展的胰岛素依赖型糖尿病,进一步证实了ＩＣＡ是ＩＤＤＭ的重要免疫学标志。对ＮＩＤＤＭ进行ＩＣＡ检测,有利于早期鉴别,进行病因分型,合理治疗。     

糖尿病患者谷氨酸脱羧酶自身抗体测定的临床意义

应用间接ＥＬＩＳＡ法测定３７例胰岛素依赖型糖尿病（ＩＤＤＭ）患者血清谷氨酸脱羧酶（ＧＡＤ）自身抗体，并以非胰岛素依赖型糖尿病（ＮＩＤＤＭ）、及其它自身免疫性疾病、正常人各３０例作对照，同时用间接免疫荧光法测定胰岛细胞浆抗体（ＩＣＡ）作比较。结果：ＩＤＤＭ患者的阳性率高达８３．８％（３１／３７），ＮＩＤＤＭ患者为１６．７％（５／３０），而其它自身免疫性疾病及正常人无１例阳性。在ＩＤＤＭ患者中，ＧＡＤ     

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。     

胰岛素依赖型糖尿病HLA相关抗原与ICA关系的研究

胰岛素依赖型糖尿病ＨＬＡ相关抗原与ＩＣＡ关系的研究单忠艳，滕卫平，邸国勋，宋芳吉，杨晓娟胰岛素依赖型糖尿病（ＩＤＤＭ）是与遗传有关的自身免疫性疾病。人类白细胞抗原（ＨＬＡ）是识别ＩＤＤＭ遗传易感性的标志，胰岛细胞抗体（ＩＣＡ）被认为是ＩＤＤＭ存在自身...     

血清胰岛细胞抗体的测定及临床意义

作者采用Ｏ型血人新鲜胰腺冰冻切片作抗原，建立了血清胰岛细胞胞浆抗体（ＩＣＡ）的间接免疫荧光测定方法。对１５７例糖尿病患者（其中ＩＤＤＭ８２例、ＮＩＤＤＭ７５例）和８４例正常人进行了血清ＩＣＡ检测。结果，ＩＤＤＭ组、ＮＩＤＤＭ组和对照组的ＩＣＡ阳性率分别为３１．５％、１３．３％和１．１％，３组间差异有非常显著性（Ｐ＜０．００５）。ＩＤＤＭ组中，病程６个月以内者ＩＣＡ阳性率为４１．７％，病程超过６个月者为２２．６％，差异无显著性。１０例ＩＣＡ阳性的ＮＩＤＤＭ病人中，４例为口服降糖药继发失效者。提示ＩＣＡ是ＩＤＤＭ的自身免疫血清学标志，对糖尿病的病因学诊断分型及判断ＮＩＤＤＭ口服降糖药继发失效有重要意义。     

缓慢进展的胰岛素依赖型糖尿病

０６１　缓慢进展的胰岛素依赖型糖尿病［日］／小林哲郎∥糖尿病。－１９９４，３７（２）．－１０３～１０５胰岛素依赖型糖尿病（ＩＤＤＭ）多急性起病，胰岛细胞抗体（ＩＣＡ）大都阳性。作者等在研究ＩＤＤＭ患者ＩＣＡ过程中发现作为对照组的部分ＮＩＤＤＭ患者ＩＣ...     

~（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。     

糖尿病患者血清肿瘤坏死因子 α 的水平及临床意义

为探讨血清肿瘤坏死因子α（ＴＮＦα）在糖尿病及血管并发症中的作用，采用ＥＬＩＳＡ法对６８例糖尿病患者［非胰岛素依赖型糖尿病（ＮＩＤＤＭ）４８例、胰岛素依赖型糖尿病（ＩＤＤＭ）２０例］血清ＴＮＦα水平进行了检测。结果显示：糖尿病组、ＮＩＤＤＭ组、ＩＤＤＭ组血清ＴＮＦα水平显著高于正常对照组（Ｐ＜０．０１），合并血管并发症组升高更明显（Ｐ＜０．０１）。血清ＴＮＦα水平与血糖不相关；与病程、血清甘油三酯呈正相关；与血清白蛋白呈负相关。治疗后随着病情好转，ＴＮＦα呈下降趋势。提示：血清ＴＮＦα增加是长期高血糖的结果。ＴＮＦα参与糖尿病血管并发症的发生、发展。动态检测血清ＴＮＦα水平可作为临床观察糖尿病病情变化的客观指标。     

Ⅰ型糖尿病患者外周血NK细胞活性降低

以改良铬（５１Ｃｒ）释放法检测３４例Ⅱ型糖尿病（ＮＩＤＤＭ）、２３例Ｉ型糖尿病（ＩＤＤＭ）和２８例正常人外周血ＮＫ细胞对Ｋ５６２靶细胞的杀伤活性。结果显示：①ＩＤＤＭ组患者ＮＫ细胞活性显著低于ＮＩＤＤＭ组及正常对照组，经正规治疗血糖控制以后，ＮＫ细胞活性恢复正常。②ＮＩＤＤＭ组患者血ＮＫ细胞活性在血糖控制前后无显著变化，与正常对照组比较亦无统计学差异。提示ＩＤＤＭ与机体免疫异常密切关联。     

糖尿病肾病早期筛选试验的临床意义

Ⅱ型糖尿病（ＮＩＤＤＭ）７４例，健康对照者１１例。所有受试者常规尿蛋白均阴性。以放免法（ＲＬＡ）和阻止凝集纸片法（ＡＴ）分别定量与定性检测受试者随机尿微量白蛋白（ＭＵＡ）。结果认为，糖尿病患者ＭＵＡ与血糖、糖化血红蛋白（ＨｂＡ１ｃ）及糖尿病病程相关。ＡＴ与ＲＩＡ法结果一致，ＡＴ可以作为筛选糖尿病患者尿微量白蛋白简便实用的方法之一。     

Islet autoantibody markers in IDDM: risk assessment strategies yielding high sensitivity

Summary Identification of islet autoantigens offers the possibility that antibody tests other than islet cell antibodies may be used for assessing risk of insulin-dependent diabetes mellitus (IDDM). The aim of this study was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, antibodies to glutamic acid decarboxylase (GAD)₆₅, 37,000/40,000 M_r islet tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with pre-IDDM, GAD₆₅ antibodies in 70 % of IDDM patients and 89 % with pre-IDDM, and antibodies to 37,000/40,000 M_r islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were found only in conjunction with islet cell antibodies and were more frequent in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjects who had islet cell antibodies without GAD₆₅ antibodies had antibodies to 37,000/40,000 M_r islet tryptic fragments, and all but one had disease onset before age 15 years. No sera strongly immunoprecipitated in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients had anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of the control subjects. The findings suggest that none of the single antibody specificities are as sensitive as islet cell antibodies, but that a combination of GAD₆₅ antibodies and antibodies to 37,000/40,000 M_r islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace islet cell antibodies in population screening for IDDM risk assessment. [Diabetologia (1995) 38: 816–822] Received: 17 October 1994 and in revised form: 29 December 1994     

Autoantibodies to the islet antigen ICA 69 occur in IDDM and in rheumatoid arthritis

Summary Islet cell antigen (ICA) 69 is a newly-recognized islet cell antigen to which autoantibodies have been observed in prediabetic relatives of patients with insulin-dependent-diabetes mellitus (IDDM). Here we extend the earlier analysis of ICA 69 antibodies to patients with recent-onset IDDM and to patients with other immune-mediated diseases. ICA 69 antibodies were determined by Western blot using an affinity purified recombinant fusion protein of ICA 69 and maltose binding protein. ICA 69 antibody quantities were determined as titres using a titration curve of a standard serum as reference. Mean logarithmic ICA 69 antibody titres were 3.4 (±1.4) in 99 patients with acute IDDM compared to 2.8 (±0.9) in 49 healthy blood donors (p<0.001). A higher mean ICA 69 antibody titre of 4.1 (±0.8) was observed in 16 patients with rheumatoid arthritis in comparison to acute IDDM (p<0.01) and healthy control subjects (p<0.001). The percentage of sera with ICA 69 antibody titres above the 2 SD level of normal subjects was 21% in IDDM, 31% in rheumatoid arthritis and 6% in healthy blood donors. None of the patients with autoimmune thyroid disease (n=20), inflammatory bowel disease (n=9) or multiple sclerosis (n=7) had elevated ICA 69 antibodies. In IDDM, presence of ICA 69 antibodies persisted and the titre remained the same over 18 months of follow-up. The relationship of ICA 69 antibodies to islet cell antibodies (ICA) or insulin autoantibodies (IAA) was tested. The production of ICA 69 antibodies was not associated in diabetic patients with the presence of any of the two other autoantibodies. In conclusion, this study describes ICA 69 antibodies in acute IDDM and finds them to be independent of other islet autoantibodies. In addition ICA 69 is a target of humoural autoimmunity not only in IDDM but also in rheumatoid arthritis.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell antibodies - IAA insulin autoantibodies - RA rheumatoid arthritis - RF rheumatoid factor - GAD 65 glutamic acid decarboxylase - SMS stiff-man syndrome     

Evaluation of the importance of antibodies against islet cells (ICA) and Glutamate Decarboxylase(anti-GAD) for determining prognosis of diabetes type 1 in the Polish population--5 year observation

It was recently shown that there are significant differences between the frequencies of antibodies against pancreatic islet cell antigens (ICA, GADA) in the first degree relatives of IDDM patients in different regions of Poland. There are however no published studies concerning their predictive value in the development of IDDM in the Polish population. The aim of the present study was to evaluate the PPV (positive predictive value) of ICA and GADA antibodies and to analyse diabetes-free survival in association with titre, antibodies co-existence and relatives age in the Polish population. The study was performed in 225 first degree relatives of IDDM patients with ICA and/or GADA and 100 relatives without antibodies, in whom ICA and/or GADA were performed in 1993-1994. We have observed significantly lower percentages of diabetes-free survival in subjects with ICA > 20 JDF in comparison to relatives without ICA or with ICA < 20 JDF. The highest predictive value for diabetes type 1 development was associated with the ICA > 80 JDF and with the co-existence of ICA--20-79 JDF and GADA (+). There was also a statistically lower diabetes-free survival in first degree relatives (with ICA > 20 JDF) older than 20 years of age in comparison to the younger subjects. Detection of 2 antibodies: ICA and GADA made it possible to identify 80% of first degree relatives who have developed diabetes type 1 in the following 5-6 years, this suggests that the combined measurement of ICA and GADA could be a useful marker in screening for diabetes type 1 in first degree relatives of IDDM subjects in the Polish population. For the diabetes type 1 risk assessment in relatives with ICA > 20 JDF the age of the studied subjects should be taken into consideration.     

Anti-37kDa antibodies are associated with the development of IDDM in individuals with islet cell antibodies

Summary Antibodies directed against a beta-cell specific antigen with a molecular weight of 37 kDa have recently been described. These anti-37kDa antibodies were measured by the immunoprecipitation technique in individuals at risk for insulin-dependent diabetes mellitus (IDDM), with islet cell antibodies (ICA) greater than 20 Juvenile Diabetes Foundation units (JDFU). These subjects were recruited from large population-based cohorts at various degrees of risk for developing the disease before adulthood. Anti-37kDa antibodies were measured in 25 ICA-positive first degree relatives with ICA greater than 20 JDFU, identified from a baseline cohort of 1,185 relatives (age: 0–75 years). Four relatives were positive for anti-37kDa antibodies since the first determination onwards. These relatives developed IDDM in a 2-year follow-up period. We included 300 children with an IDDM parent, and aged less than 7 years, in a prospective survey for the prediction of IDDM. Five (1.6%) showed ICA greater than 20 JDFU. None of them were found to be positive for anti-37kDa antibodies, and none have progressed to diabetes during a 2-year follow-up. Among a baseline cohort of 13,380 schoolchildren (age: 6–17 years), 28 (0.2%) were found to have ICA greater than 20 JDFU. One boy was positive for anti-37kDa antibodies on two consecutive occasions and developed IDDM after a 10-month follow-up. No other schoolchildren with ICA greater than 20 JDFU were found to be positive for anti-37kDa antibodies. Altogether 40 other ICA-positive sera (with titres <20 JDFU) were found to be negative for anti-37kDa antibodies. With our assay, anti-37kDa antibodies were found to have a 76% sensitivity (95%CI: 68–92%) at the time of diagnosis in diabetic children. The current observations are based on a short-term follow-up. An analysis based on a longer period will be extremely useful for the prediction of IDDM and the appearance of anti-37kDa antibodies.Abbreviations IDDM insulin-dependent diabetes mellitus - ICA islet cell antibodies - IAA insulin auto-antibodies - JDFU Juvenile Diabetes Foundation unit     

Islet cell surface antibodies by an ELISA method in diabetic and nondiabetic patients

Islet cell surface antibodies (ICSA) were investigated by an ELISA method using a commercial kit in 146 subjects with and without islet cell antibodies (ICA): 28 with insulin-dependent diabetes mellitus (IDDM), 24 with noninsulin-dependent diabetes mellitus (NIDDM), 22 first-degree relatives (FDR) of IDDM patients, 31 organ-specific autoimmune patients (OSAP), 21 nonautoimmune hospitalized patients (NAP), and 20 ICA-negative normal controls. Furthermore, insulin autoantibodies (IAA) were evaluated in 87 of these subjects. ICSA were found in 11% of IDDM patients and in 14% of their FDR, in 4% of NIDDM patients, in 10% of OSAP, in 10% of NAP, and in 5% of normal controls. After absorption with rat liver powder, ICSA were detected in 7% of IDDM patients, in 5% of their FDR, in 4% of NIDDM, in 6% of OSAP, in 5% of NAP and in none of normal controls. ICSA were also detected in 4% of IAA-positive compared to 3% of IAA-negative sera. Neither correlation was found between ICSA and ICA in each group of subjects, nor between ICSA and IAA, suggesting that these autoantibodies recognize different pancreatic targets. Moreover, no significant difference was observed for ICSA prevalence in the various groups of patients studied when compared with normal controls. The prevalence of ICSA assessed by this ELISA method has been compared to that reported by other workers, who employed different techniques.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamic acid decarboxylase antibodies,autonomic nerve antibodies and autonomic neuropathy in diabetic patients

Summary To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p<0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures.Abbreviations GAD Glutamic acid decarboxylase - ab antibodies - ICA islet cell antibodies - CF-ADM complement-fixing adrenal medulla antibodies - CF-SG complement-fixing sympathetic ganglia antibodies - CF-V complement-fixing vagal nerve antibodies - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - JDF Juvenile Diabetes Foundation     

Islet cell antibodies are not specifically associated with insulin-dependent diabetes in Tanzanian Africans

The prevalence of islet cell antibodies (ICA and CF-ICA) together with other organ-specific auto-antibodies was investigated in 122 newly presenting black Tanzanian diabetic patients in Dar es Salaam. ICA were found in three (8.6%) IDDM patients and five (6.8%) insulin-requiring NIDDM patients; six of the eight were also CF-ICA positive. Altogether 22% of patients showed one or more positive autoantibody result but there was no clustering of response, and no association of ICA with other antibodies except for two NIDDM subjects who showed one other positive result. There were no differences between insulin-requiring (IDDM) and NIDDM subjects or between younger (less than 30 years) and older patients. We conclude that there is no major association between diabetes and islet cell antibodies in black Tanzanians.     

NIDDM患者24小时血压监测的临床意义

用无创性动态血压监测（ＡＢＰＭ）对３０例血压正常的ＮＩＤＤＭ患者进行２４小时动态血压监测，并探讨其与自主神经病变和肾病的关系。结果：ＮＩＤＤＭ患者２４小时平均收缩压（１６．５±２．６ｋＰａ）、夜间收缩压（１６．３±３．１ｋＰａ）均较对照组（分别为１４．６±１．１ｋＰａ和１４．０±１．６ｋＰａ）明显增高；夜间收缩压负荷值增高（有１７例，占５７％）；夜间收缩压下降百分率降低（５．７％±５．０％对１０．４％±５．７％）；有神经病变的ＮＩＤＤＭ患者夜间收缩压下降百分率（３．６％±３．３％）及昼－夜尿白蛋白排泄差值（８．８％±８．５％）均低于无神经病变患者（分别为９．９％±５．１％和２０．６％±１１．１％）。提示糖尿病患者血压昼夜节律减弱或消失以及夜间血压增高可能参与糖尿病肾病的发生。     

Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study

Summary To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37%) siblings were constantly seronegative and 29 (63%) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p<0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells.Abbreviations IDDM Insulin-dependent diabetes mellitus - ICA islet cell autoantibodies - CMV cytomegalovirus - EIA enzyme immunoassay - EIU enzyme immunoassay unit