1型糖尿病基因治疗研究进展

1型糖尿病自身免疫发病机制涉及到免疫耐受、自身抗原提呈、T细胞活化以及细胞凋亡等异常。转染β细胞特异性抗原基因可诱导免疫耐受,转染前炎性因子受体拮抗蛋白基因及干扰协同刺激信号可阻止抗原提呈细胞及T细胞活人,可通过抑制细胞凋亡来阻断针对胰岛的自身免疫反应,最终达到治疗糖尿病的目的。此外,通过转基因技术可使非胰岛β细胞获得合成分泌胰岛素的能力,用于治疗胰岛素缺乏所致糖尿病亦将成为可能。     

IA-2抗体预报1型糖尿病的研究进展

胰岛β细胞瘤相关蛋白-2(IA-2)是从人类胰岛细胞瘤减法文库中分离出的含有979个氨基酸的跨膜蛋白,是蛋白酪氨酸磷酸酶家族中的成员,主要抗原决定簇在胞内功能区.IA-2主要存在胰腺、脑组织的神经内分泌细胞中.IA-2与胰岛细胞抗体(ICA)512功能相同,与IA-2β,37KDa片段,40KDa片段有关.65%(55%～75%)新诊断的1型糖尿病病人的血清中存在IA-2抗体,与谷氨酸脱羧酶抗体(GADA),胰岛素自身抗体(IAA)联合测定在1型糖尿病预报中有重要意义.     

特发性1型糖尿病诊断的若干问题

糖尿病的分型在临床上有时候是很困难的，随着1997年美国糖尿病学会(ADA)新的分型诊断标准的提出以及世界卫生组织(WHO)进一步地确认，糖尿病的分型已按照病因和发病学划分。急性起病的1型糖尿病，检测抗体如阳性可诊断为自身免疫性1型糖尿病；如果抗体阴性，可诊断为特发性(非自身免疫性)1型糖尿病。     

胰岛自身抗体与1型糖尿病

1617例糖尿病患者中自身抗体阳性率29．7％。单一抗体的阳性率明显低于3种抗体联合检测。多种胰岛自身抗体联合检测可提高1型糖尿病早期诊断的敏感性。谷氨酸脱羧酶抗体为成年糖尿病患者预示胰岛素依赖的较好的筛查试验，与酪氨酸蛋白磷酸酶抗体联合检测可达近100％的预报价值；而青少年糖尿病患者则还需检测胰岛细胞抗体。     

1型糖尿病基因治疗研究进展

1型糖尿病自身免疫发病机制涉及到免疫耐受、自身抗原提呈、T细胞活化以及细胞凋亡等异常。转染 β细胞特异性抗原基因可诱导免疫耐受 ,转染前炎性因子受体拮抗蛋白基因及干扰协同刺激信号可阻止抗原提呈细胞及T细胞活化 ,并可通过抑制细胞凋亡来阻断针对胰岛的自身免疫反应 ,最终达到治疗糖尿病的目的。此外 ,通过转基因技术可使非胰岛 β细胞获得合成分泌胰岛素的能力 ,用于治疗胰岛素缺乏所致糖尿病亦将成为可能。     

成人晚发1型糖尿病相关抗体检测意义

将３２５例成人晚发１型糖尿病患者分成胰岛素（ＬＮＳ）分泌缺乏及非ＩＮＳ分泌缺乏两组,用间接酶联免疫吸附（ＥＬＩＳＡ）法测定其县岛细胞坑体（ＩＣＡ）、胰岛素抗体（ＩＡＡ）及谷氨酸脱羧酶抗体（ＧＡＤ－Ａｂ）,比较其相关性。结果两组ＩＣＡ、ＧＡＤ、Ａｂ阳性率、酮症发生率及体重指数有显著性差异。证明ＩＣＡ、ＧＡＤ－Ａｂ可作为成人晚发１型糖尿病的早期筛选指标。     

1型糖尿病与HLA-DQB1基因及自身抗体相关性研究

采用基因分型技术,确定32例1型糖尿病患者及23例正常对照的HLA-DQB1等位基因.用酶联免疫吸附法测定血清中谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)及胰岛素自身抗体(IAA).结果在1型患者中,DQB1*0201、*0303、*0604等位基因频率显著高于对照(P＜0.05),DQB1*0301则低于对照(P＜0.05),其余DQB1等无显著性差异.等位基因为DQB1*0201的患者中GADA阳性率显著高于阴性率.结论在中国汉族人群中,DQB1*0201、*0303、*0604是1型糖尿病易感性等位基因,DQB1*0301是1型糖尿病保护性等位基因.DQB1*0201可能对GADA的产生起允许作用.     

自身抗体与1a型糖尿病的诊断和预测

1a型和1b型糖尿病最重要的区别是前者存在胰岛自身抗体。本文主要就自身免疫性1型糖尿病的两个主要问题进行阐述：①哪些抗体可作为自身免疫性1型糖尿病的诊断标志;②用于诊断1型糖尿病的胰岛自身抗体能否预测非糖尿病患者群的1型糖尿病的发生。     

1型糖尿病神经病变基因学研究进展

近年研究发现1型糖尿病神经病变是一种多基因病,其发生、发展存在着遗传倾向性,目前已发现主要与线粒体DNA突变,营养因子相关的早期基因表达延迟,醛糖还原酶、超氧化物歧化酶基因、Na+/K+ATP酶ATP1-A1基因多态性,丝裂素活化蛋白激酶基因,感觉神经元的神经丝和微管蛋白mRNA表达降低有关。一氧化氮合酶基因与神经病变的关系比较复杂,有待进一步研究。     

1型糖尿病的免疫耐受治疗

1型糖尿病的发病机制是自身免疫性胰岛炎.其胰岛素缺乏是由于胰腺中大量胰岛β细胞被免疫系统攻击所致.通过各种不同的途径建立胰岛β细胞免疫耐受,包括造血干细胞的移植、过继不同功能状态的树突状细胞、口服胰岛素及其相关疫苗的输入、谷氨酸脱羧酶65疫苗、抗CD3、CD20单克隆抗体以及联合免疫干预等免疫耐受治疗,可延缓l型糖尿病...     

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276±78 vs 149±46 units/l). Type 2 diabetic patients had considerably higher levels of apo (a) than matched controls (471±89 vs 221±61 units/l,P=0.06), though the difference was not statistically significant. However, concentrations of apo (a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.     

1型糖尿病免疫学研究进展

1型糖尿病是一种器官特异性自身免疫性疾病.其发病机制复杂,在遗传、环境、免疫等诸多因素的共同作用下,自身抗原免疫耐受丧失,免疫调节失衡,导致针对胰岛β细胞的自身免疫性破坏,导致糖尿病的发生.但其具体病因目前尚不明确,再生基因家族、胰-十二指肠同源盒因子1、嗜铬粒蛋白A、辅助性T细胞(Th)17及胰岛稳态蛋白等均参与1型糖尿病发病的不同环节,同时这些新的免疫学因子的发现,为1型糖尿病的诊断及治疗提供了新的靶点.     

Frequency of Hashimoto's thyroiditis in children with type 1 diabetes mellitus

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P<0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated withl-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.A collaborative study of the AASGPED-Alpe Adria Study Group of Pediatric Endocrinology and Diabetology     

1型糖尿病诊断初期某些细胞因子的改变

目的 探讨细胞因子（CK）在1型糖尿病中的作用,了解其与糖尿病HLA易感基因及糖代谢的关系。方法 放免法或酶免法检测新诊断1型糖尿病病人血清6种CK、胰岛素和C肽;斑点杂交法检测4种糖尿病HLA易感基因;微柱法测定HbA1c。用SPSS软件处理数据。结果 病人组IL－2、IL－4低于对照组,IL－1β、IFN-γ/IL-4、IL－12／IL－4比值,都显著高于对照组;IFN－γ、IL-4、IL－1β分别与IL－12正相关,IL－12／IL－4与IFN－γ／IL－4正相关;空腹胰岛素与IL－1β和空腹C肽与IL－12分别呈正相关。结论 新诊断1型糖尿病病人存在IL－4、IL－2低下及IL－2β的分泌增高;1型糖尿病病人存在TH1优势;IL－12与IL－4正相关,表明了它们对TH1、TH2细胞的调节关系;CK与HbA1无显著相关性;HLA－DQB1＊0201携带者TNF－α较高。     

1型糖尿病的DiaPep277免疫治疗

1型糖尿病（T1DM）的病理基础是胰岛β细胞的自身免疫性破坏,因此阻止该免疫进程对预防或治疗T1DM尤为重要.DiaPep277是一种由24个氨基酸组成的肽段,衍生于热休克蛋白60（HSP60）的C-末端区域.研究证明,它对糖尿病动物模型的自身免疫性T细胞具有免疫调节作用.临床研究表明,DiaPep277对初发T1DM患者的胰岛β细胞有保护作用,并具有安全性.     

1型糖尿病的免疫干预及其干细胞治疗

1型糖尿病以自身免疫性胰岛炎为病理特征.免疫干预可作用于胰岛自身免疫过程的不同环节,阻碍胰岛炎的发生与发展.干细胞可诱导分化为胰岛素分泌细胞,且具有免疫调节功能.现对免疫干预及干细胞移植治疗1型糖尿病等方面的最新研究进展进行综述.     

间充质干细胞联合胰岛细胞治疗1型糖尿病研究进展

近年来,国内外兴起的胰岛移植术治疗l型糖尿病,因炎症介导的免疫反应以及营养因子缺乏而导致移植后3-5年内仍需注射小剂量的胰岛素,而间充质干细胞与胰岛细胞联合,不仅具有免疫调节作用还能分泌营养因子促进胰岛细胞活性和功能,但其在体内的致瘤性以及促进肿瘤细胞转移这些潜在不良反应会一定程度影响其临床应用.本文就间充质干细胞与胰...     

Exocrine pancreas functions in children with type 1 diabetes mellitus

Background and study aimWe evaluated exocrine pancreas functions using a noninvasive indicator in a case–control study conducted on children and adolescents diagnosed with type 1 diabetes mellitus.Patients and methodsSixty-seven patients who participated in a summer camp were enrolled in this study. Nineteen healthy children in the same age group were assigned to the control group. Fecal pancreatic elastase was assayed using the enzyme-linked immunosorbent assay technique. Values higher than 200 µg/g were considered an indication of sufficient exocrine pancreatic functioning, values between 100 µg/g and 200 µg/g were considered mild exocrine pancreatic insufficiency, and values below 100 µg/g were considered severe exocrine pancreatic insufficiency.ResultsThe mean concentration of fecal elastase was 158.38 ± 59.67 µg/g. The patients were assigned to three groups according to these values. Thirteen patients (22%) had sufficient fecal elastase levels, whereas 36 patients (62%) had mildly insufficient levels, and nine patients (16%) had severely insufficient fecal elastase concentrations. The levels of fecal elastase, amylase, lipase, and zinc were significantly different between the patients and controls (p < 0.001). Only the duration of diabetes was significantly different between patients with different severities of exocrine pancreatic insufficiency (p = 0.037). Additionally, the group with severe pancreatic insufficiency had more frequent hypoglycemic attacks.ConclusionExocrine pancreatic insufficiency may develop in children with diabetes, and hypoglycemia attacks are observed more frequently depending on the severity of pancreatic insufficiency.     

Transplantation for the treatment of type 1 diabetes

Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin Alc levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events （even with only partial islet function evident）. Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pretransplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the longterm viability and function of the graft to maintain improved glucose control over time.