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     

线粒体tRNA~（Leu（UUR））基因突变糖尿病──患病率估测、临床特点及基因诊断途径

用基因诊断技术在２０７例无亲缘关系的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者中，筛查线粒体ｔＲＮＡＬｅｕ（ＵＵＲ）基因突变糖尿病，２例基因诊断阳性。本病在具不常见临床表现的ＮＩＤＤＭ亚群中占２．４％～１１．１％。对２例阳性者的家系进行临床及基因分析，检测２５个家系成员中，１０个基因诊断阳性。提出对于起病早、对口服降糖药继发失效需改用胰岛素治疗、有胰岛β细胞功能明显减退、消瘦、神经性耳聋、有糖尿病及／或听力障碍家族史且符合或不能除外母系遗传一种或多种情况的ＮＩＤＤＭ者应疑及本病。可用方法简便、易于判断的等位基因特异引物扩增（ＡＳＰＡ）或ＰＣＲ２０６ｂｐ／ＡｐａＩ或ＨａｅⅢ技术进行临床基因诊断。     

加强对成人晚发自身免疫性糖尿病的研究

加强对成人晚发自身免疫性糖尿病的研究罗敏非胰岛素依赖型糖尿病（ＮＩＤＤＭ）是一组异质性疾病，早在７０年代，有人就观察到部分ＮＩＤＤＭ患者血胰岛细胞抗体（ＩＣＡ）阳性、无肥胖、血Ｃ肽水平低，易出现继发性口服降糖药治疗失效。以后大量研究表明，确实有一组Ｎ...     

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。     

线粒体tRNA^Leu（UUR）基因突变糖尿糖—患病率估测,临床特点及…

用基因诊断技术在２０７例无亲缘关系的非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者中，筛查线粒体ｔＲＮＡ＾Ｌｅｕ（ＵＵＲ）基因突变糖尿２，２例基因诊断阳性。本病在具有不常临床表现的ＮＩＤＤＭ亚群中占２．４％－１１．１％。对２例阳性者的家系进行临床及基因分析，检测２６个家系成员中，１０个基因诊断阳性，提出于起病早、对口服降糖药继发失效需改用胰岛素治疗、有胰β细胞功能明显减退、消瘦、神经性耳聋、有糖尿病及／或     

磺脲类口服降糖药继发失效及其处理

磺脲类口服降糖药继发失效及其处理傅祖植磺脲类口服降糖药（ＳＵｓ）是治疗非胰岛素依赖型糖尿病（ＮＩＤＤＭ）的主要药物。通常将应用ＳＵｓ后在１个月内效果不佳者称为原发性失效。若初始治疗能有效地控制血糖，其后效果逐渐降低者，称为继发性失效（ｓｅｃｏｎｄａｒ...     

老年人非胰岛素依赖型糖尿病与脂蛋白（a）的关系

目的了解老年非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者及其慢性并发症和并存症者血清脂蛋白（ａ）〔Ｌｐ（ａ）〕变化情况。方法测定８９例老年ＮＩＤＤＭ和６１例非老年ＮＩＤＤＭ患者并以６２例老年非糖尿病健康者作对照的血清Ｌｐ（ａ）和其它血脂水平，并分析了老年ＮＩＤＤＭ组并发症及并存症对血清Ｌｐ（ａ）的影响。结果３组血清Ｌｐ（ａ）浓度差异无显著性（Ｐ＞０．０５），Ｌｐ（ａ）与血清总胆固醇、甘油三酯、高密度脂蛋白－胆固醇及其亚型、低密度脂蛋白－胆固醇、载脂蛋白Ａ１和Ｂ水平无明显相关性（ｒ＝－０．０４１～０．１９７，均为Ｐ＞０．１）。老年ＮＩＤＤＭ组合并高血压、糖尿病性视网膜病变和肾病变者的血清Ｌｐ（ａ）浓度明显高于无合并相应疾病者（Ｐ＜０．０５或Ｐ＜０．００１）；血清尿素氮、肌酐、尿微量白蛋白排泄率升高、尿蛋白定性阳性者血清Ｌｐ（ａ）明显高于肾功能正常者（均为Ｐ＜０．００５）；血糖化血红蛋白Ａ１ｃ≥８％者其Ｌｐ（ａ）明显高于＜８％者（Ｐ＜０．００５）。结论老年ＮＩＤＤＭ患者血清Ｌｐ（ａ）浓度与对照组差异无显著性；合并高血压、糖尿病性视网膜病变和肾病变及肾功能异常、糖化血红蛋白Ａ１ｃ≥８％者血清Ｌｐ（ａ）明显升高。     

NIDDM患者口服降糖药失效后的胰岛素使用问题

ＮＩＤＤＭ患者口服降糖药失效后的胰岛素使用问题ＣｏｃｋｒａｍＣ（向红丁译）在香港和中国大陆，９７％的糖尿病患者属于非胰岛素依赖型糖尿病（ＮＩＤＤＭ）。在香港，工龄阶段成人中糖尿病患病率为４．５％，而６０岁以上人群中糖尿病患病率超过１０％。对ＮＩＤＤＭ...     

非胰岛素依赖型糖尿病患者血管紧张素转换酶与慢性并发症的关系

目的探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者血清血管紧张素转换酶（ＳＡＣＥ）水平及其与各种慢性并发症的关系。方法６７例ＮＩＤＤＭ患者用紫外法测定ＳＡＣＥ水平。结果ＮＩＤＤＭ全组ＳＡＣＥ为（３３９±１２４）Ｕ／Ｌ，明显高于正常人［（２８．１±５．７）Ｕ／Ｌ］，Ｐ＞００１。其中超出正常范围（３９５Ｕ／Ｌ）者１８例，占２７％；糖尿病肾病（ＤＮ）者（３０例）ＳＡＣＥ更高［（４２６±１０．６）Ｕ／Ｌ］，而无ＤＮ者［３７例，（２６９±５．７）Ｕ／Ｌ］与正常人无异。结论ＮＩＤＤＭ患者ＳＡＣＥ升高与病程、ＤＮ、视网膜病变（ＤＲ）、神经病变、心血管病变等慢性并发症有关。为临床应用ＡＣＥ抑制剂防治糖尿病慢性并发症提供部分依据。     

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。     

IDDM自身抗体与胰岛功能的研究

本文测定了36例新诊断、未使用过外源胰岛素的IDDM患者的血清胰岛细胞抗体(ICA)、血清胰岛素自身抗体(IAA)及血清C肽和胰岛素水平,并以72例新诊断的NIDDM和36例正常人作为对照。研究表明:自身免疫在IDDM病因中占有重要地位;临床发病时ICA、IAA阳性可以作为IDDM自身免疫的标志,但不能反映胰岛β细胞功能损害的程度。     

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.     

Antibodies to Glutamic Acid Decarboxylase in Japanese Diabetic Patients with Secondary Failure of Oral Hypoglycaemic Therapy

Some patients with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) are positive for antibodies to glutamic acid decarboxylase (anti-GAD), which have been shown to be a useful marker for the diagnosis and prediction of insulin-dependent (Type 1) diabetes mellitus (IDDM). Anti-GAD positive NIDDM patients tend to develop insulin deficiency. We investigated the prevalence of anti-GAD in 200 NIDDM with secondary failure of oral hypoglycaemic therapy (SF) and 200 NIDDM well controlled by diet and/or sulphonylurea agents (NSF). Twenty-two of 200 (11 %, p < 0.05) SF patients and 6 of 200 (3 %) NSF patients were anti-GAD positive. The positive rate for anti-GAD was as high as 23.8 % in the non-obese and insulin deficient SF patients. The SF patients with anti-GAD tended to be non-obese and to have an impaired release of endogenous insulin. The interval before development of secondary failure was not associated with the presence of anti-GAD in this study. In conclusion we found that anti-GAD was positive in as many as 11 % of the SF patients, suggesting that autoimmune mechanisms may play an important role in the pathogenesis of secondary failure of sulphonylurea therapy. © 1997 by John Wiley & Sons, Ltd.     

胰岛细胞抗体ABC法检测及临床意义初步探讨

胰岛素依赖型糖尿病（ＩＤＤＭ）与机体的免疫功能紊乱有密切的关系。胰岛细胞抗体（ＩＣＡ）是ＩＤＤＭ患者主要的免疫学标志之一。可采用免疫组织化学技术作ＩＣＡ定性检测。我们首次应用“Ｏ”型血正常人胰腺石蜡切片作为抗原，ＡＢＣ法（卵白素－生物素化过氧化物酶复合物法）检测血清中ＩＣＡ。结果：１７例ＩＤＤＭ患者，阳性检出率５２．９４％；２０例ＮＩＤＤＭ及２０例非糖尿病患者无阳性反应。与国外报道比较，其方法的可     

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)     

Non-human primate pancreas as a substrate for the detection of islet-cell antibodies in human sera

In an effort to find out if the use of non-human primate pancreas may improve the sensitivity of the islet cell antibody (ICA) test, the sera from patients with type 1 diabetes (insulin-dependent IDDM) and controls were investigated by indirect immunofluorescence (IFL) on both human and baboon substrates. The mean titers of positives were insignificantly higher (1:24.9) on baboon as compared to human tissue (1:22.3). Of 50 sera from IDDM patients positive for ICA on human tissue, 47 were also positive on baboon pancreas. Of 40 ICA-negative IDDM sera two were judged positive on baboon substrate. ICA were positive on human/baboon pancreas in 3/4 out of 50 first-degree relatives of IDDM patients, 2/2 of 50 sera from patients with autoimmune diseases, 0/0 of 50 sera from type 2 diabetics and 2/1 of 100 mixed hospital controls. A disadvantage of baboon pancreas for ICA testing by IFL is the high background fluorescence given by the exocrine pancreas. With baboon tissue, three highly positive results would have been missed with undiluted sera which are usually used in this assay. It is therefore suggested that human pancreas should still be preferentially used for ICA determination, but baboon tissue may be a valuable substitute.     

Exocrine Pancreatic Ductograms in Insulin-dependent Diabetes Mellitus

Objectives: To examine the prevalence of abnormal pancreatic ductograms in patients with insulin-dependent diabetes mellitus (IDDM) and to determine the clinical cbaracteristics of those patients. Methods: Panereatie exocrine morphology was studied by endoscopie retrograde pancreatography (ERP) in 43 patients with IDDM, 12 patients with islet cell antibody (ICA)-positive non-insulin-dependent diabetes mellitus (NIDDM), and 22 patients with ICA-negative NIDDM. Resuits: ERP revealed a significantly higher prevalence of abnormal pancreatic ducts (dilation and stenosis, tortnosity, obstruction, and intraductal calculi) in the patients with IDDM (17/43, 40%) than in the patients with ICA-negative NIDDM (2/22, 9%, p = 0.018). IDDM patients who slowly progressed to insulin dependency more than 13 months after the onset of diabetes had a higher frequency of abnormal pancreatic ducts (13/22, 59%) than those who needed insulin therapy within 12 months after the onset (4/21, 19%, p = 0.016). There was no difference in duration of diabetes between the two groups. ICA-positive NIDDM patients also had a higher frequency of abnormal pancreatic ducts (7/12, 58%) than ICA-negative NIDDM patients (2/22, 9%, p = 0.0074). Conclusions: These results indieate that a high proportion of IDDM patients who have prolonged histories of non-insulin dependency with ICA suffer pancreatic exocrine impairment. A similarity between IDDM with a slowly progressive clinical course and fibrocalculous pancreatic diabetes seen in tropical countries also was suggested.     

Effects of Insulin on Body Composition in Patients with Insulin-dependent and Non-insulin-dependent Diabetes

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (∼0.6 units kg⁻¹ day⁻¹). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA_1c was greater in IDDM (5.2 ± 0.7 %) than in NIDDM (2.0 ± 0.4 %, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 ± 1.2 vs 3.77 ± 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 ± 9.3 %) and fat mass in NIDDM (59.9 ± 8.4 %). The increase in lean mass was greater in IDDM than NIDDM (5.6 ± 1.1 vs 1.4 ± 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 ± 0.8 vs 2.4 ± 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 ± 0.6 kg, NIDDM: 2.0 ± 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 ± 0.05 vs 1.09 ± 0.09, p < 0.01) and then increased in IDDM by 0.32 ± 0.15 (p = 0.07) and in NIDDM by 0.22 ± 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.     

Non-insulin-dependent diabetes and renal replacement therapy

Reports of renal replacement therapy in diabetes usually refer to patients with insulin-dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non-insulin-dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 +/- 9 years, mean +/- SD) compared to the IDDM patients (39 +/- 10 years, p less than 0.001), and had a shorter duration of diabetes (13 +/- 8 years versus 23 +/- 8 years, p less than 0.001). Asians and Afro-Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p less than 0.0001). Non-diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p less than 0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non-European and more often have non-diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.