暴发性1型糖尿病的研究进展

暴发性1型糖尿病以急骤起病、代谢紊乱严重、胰酶升高并缺乏糖尿病相关抗体为特征,属于1B型糖尿病.本文对暴发性1型糖尿病的临床及免疫学特征、发病机制、诊断要点、与妊娠及分娩的关系、治疗及预后等方面的最新研究进展进行综述.     

暴发性1型糖尿病：一种不容忽视的糖尿病急危重症

暴发性1型糖尿病(fulminant type 1 dialaetes,F1D)是日本Imagawa等[1]2000年提出的1型糖尿病的新亚型.该型糖尿病呈超急性起病,如未及时诊断和治疗,常导致患者在短期内死亡,是代谢内分泌疾病中的急危重症.鉴于此,本文就暴发性1型糖尿病的流行病学、临床特征及可能发病机制予以介绍,以引起对该病的重视和研究.     

暴发性1型糖尿病临床流行病学调查

目的了解住院糖尿病患者中暴发性1型糖尿病的患病状况。方法采用Hanafusa提出的标准诊断暴发性1型糖尿病。系统性回顾2001～2008年本院内分泌科住院糖尿病患者情况,分析暴发性1型糖尿病所占比例。结果8年间本院内分泌科住院糖尿病患者共8801例,其中新诊断急性起病1型糖尿病患者107例,暴发性1型糖尿病患者为11例。暴发性1型糖尿病约占本院连续住院糖尿病患者的1‰,新发1型糖尿病患者的10％。未观察到暴发性1型糖尿病发病逐年增加及月份聚集现象。结论暴发性1型糖尿病呈散发,成年人中常见,临床中应注意鉴别诊断。     

暴发性1型糖尿病合并败血症一例诊治分析

本文报告1例暴发性1型糖尿病合并败血症的诊断和治疗情况,并对其发病机理进行讨论。暴发性1型糖尿病起病急骤,病情严重,在较短的高血糖时间内发展成糖尿病酮症酸中毒,起病时胰岛β细胞的功能近乎完全损害,但糖尿病自身抗体多数呈阴性。而糖尿病患者因长期处于高血糖、机体代谢紊乱和免疫功能低下状态,易患多种感染性疾病,糖尿病病理状态时,机体内致病菌生长繁殖较快,病原菌难以完全去除,且感染易反复发作;同时感染可使高血糖及代谢紊乱加剧,二者相互影响,给患者健康状况及预后情况带来很大威胁。本病例起病前曾有上呼吸道感染病史,推测暴发性1型糖尿病的发生可能与病毒感染对胰岛β细胞的损伤有关,这为临床上探讨1型糖尿病的发病机理提供了线索。临床医生应对暴发性1型糖尿病提高认识、及早鉴别、积极救治。     

暴发性1型糖尿病

1型糖尿病的主要病因是胰岛β细胞遭到严重破坏导致胰岛素分泌缺乏。根据美国糖尿病协会（ADA）和世界卫生组织（WHO）的糖尿病分型标准,1型糖尿病可分为自身免疫性（1A）和特发性（1B）糖尿病。本文就暴发性1型糖尿病的流行病学、发病机制、临床表现、诊疗要点作一综述。以提高广大临床医师对此病的认识。     

产后血淀粉酶极度升高的暴发性1型糖尿病1例报告

暴发性1型糖尿病(FDM)是一种凶险的、有别于典型T1DM的免疫性T1DM新亚型,诊断及治疗不及时可危及生命,是内分泌代谢性疾病中的急危重症,其发病与妊娠及产后相关。本文对1例产后血淀粉酶(AMS)极度升高的FDM作以报告,并对该病发病情况、发病机制及相关生化指标进行分析讨论,旨在提高临床工作者的重视,做到早期诊断,积极抢救。     

六例暴发性1型糖尿病患者临床特征分析

目的 比较分析暴发性1型糖尿病及经典1型糖尿病的临床特征,探讨暴发性1型糖尿病的发病机制.方法 入选2005年9月至2009年9月在我院内分泌科住院的以酮症酸中毒为首发症状的暴发性1型糖尿病患者6例(暴发性1型糖尿病组)和以酮症酸中毒为首发症状的初发经典1型糖尿病患者24例(经典1型糖尿病组),回顾性分析两组患者的临床特征,包括发病年龄、糖尿病病程、咽痛、咳嗽、发热等流感样症状、恶心、呕吐、腹痛等消化道症状、入院时随机血糖、糖化血红蛋白、C肽、丙氨酸转氨酶、肌酸激酶、肌酐、血钾、白细胞计数等.计量资料和计数资料分别采用t检验或x2检验进行统计分析.结果 与经典1型糖尿病组相比,暴发性1型糖尿病组发病年龄升高[分别为(46±6)、(19±6)岁,t=9.89,P＜0.01],糖尿病病程明显缩短[分别为(3.5±2.7)、(52.5±32.6)d,t=3.63,P＜0.01],咽痛、咳嗽、发热等流感样症状明显增多[分别为50%(3/6)、0(0/24),x2=13.33,P＜0.01],恶心、呕吐、腹痛等消化道症状亦增多[分别为83%(5/6)、0(0/24),x2=24.00,P＜0.01].与经典1型糖尿病组相比,暴发性1型糖尿病组入院时随机血糖升高[分别为(44±7)、(23±4)mmol/L,t=9.22,P＜0.01],糖化血红蛋白降低[分别为(7.1±1.0)%、(14.4±2.2)%,t=7.66,P＜0.01],餐后2 h C肽减少[分别为(0.21±0.17)、(0.58±0.39)μg/L,t=2.29,P＜0.05],丙氨酸转氨酶增高[分别为(206±124)、(10±2)U/L,t=8.18,P＜0.01],肌酸激酶升高[分别为(1038±447)、(79±10)U/L,t=11.11,P＜0.01],肌酐增加[分别为(179±39)、(55±16)μmol/L,t=12.33,P＜0.01],血钾升高[分别为(5.2±0.7)、(3.4±0.8)mmol/L,t=5.07,P＜0.01],白细胞计数增多[分别为(21.0±8.1)×109个/L、(6.0±1.9)×109个/L,t=8.64,P＜0.01].结论 暴发性1型糖尿病患者存在胰岛β细胞功能衰竭,代谢紊乱更为严重,免疫反应更加强烈,容易导致多脏器功能损害.     

酮症倾向糖尿病研究进展

酮症倾向糖尿病是一种异质性综合征,包括1型糖尿病和酮症倾向的2型糖尿病.后者的发病机制可能同糖、脂毒性所导致的严重外周胰岛素抵抗,胰岛β细胞凋亡或功能异常以及某些遗传缺陷有密切的关系.其临床特点是起病急,以酮症为首发症状.1型糖尿病需胰岛素终身治疗,对于酮症倾向的2型糖尿病,其发病机制、分型以及治疗尚无统一的标准.通过对其深入研究,有助于对糖尿病发病机制的认识及治疗方案的制订.     

暴发性1型糖尿病研究新进展

暴发性1型糖尿病(FT1DM)是一种T1DM亚型,以迅速进展的胰岛β细胞破坏、高血糖症状和DKA,并缺乏糖尿病相关抗体为特征,被归入1B型糖尿病,属于糖尿病的急危重症。FT1DM发病与人类白细胞抗原基因型有关,免疫及肠道病毒等参与发病,但发病机制尚不明确。FT1DM与T2DM有关,既往T2DM病史者不能排除FT1DM。孕期胰岛自身免疫可能参与并促进FT1DM的发展,孕妇是该病高发人群,胎儿预后极差。     

妊娠合并暴发性1型糖尿病酮症酸中毒昏迷1例报道

暴发性1型糖尿病(F1D)以起病急骤、代谢异常严重、胰酶升高,并缺乏糖尿病相关抗体为特征,属1B型糖尿病。妊娠期出现的T1DM基本上均为F1D,一旦发生即可能出现死胎、孕妇死亡等严重后果。本文报道1例妊娠合并F1D患者,讨论其发病情况、机制及诊断要点,旨在提高对该病的认识,改善预后。     

Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners

Fulminant type 1 diabetes is a recently discovered subtype of type 1 diabetes. It is defined as diabetes in which the process of beta-cell destruction and the progression of hyperglycemia and ketoacidosis are extremely rapid. The pathogenesis of this disease remains to be clarified, but the involvement of both genetic background-especially human leukocyte antigen genes-and viruses has been suggested. Fulminant type 1 diabetes has the following clinical characteristics: duration of hyperglycemic symptoms is 4 days on average; there is a high prevalence of preceding common-cold-like and gastrointestinal symptoms; there is a near-normal level of glycated hemoglobin in spite of very high plasma glucose levels associated with ketoacidosis; the disease is sometimes related to pregnancy; and there are increased serum pancreatic enzyme levels, absent C-peptide levels, but virtually no detectable autoantibodies against constituents of pancreatic beta cells. The presence of the above characteristics strongly indicates the diagnosis of fulminant type 1 diabetes. Once the diagnosis of this disease is suspected, treatment of diabetic ketoacidosis must be started immediately, as in all other cases of type 1 diabetes. Otherwise, the death of the patient is likely to occur within 24 h. All medical practitioners must remember that this extremely rapidly progressing type of diabetes does exist, and they must pay special attention not to overlook it.     

暴发性Ⅰ型糖尿病2例并文献复习

目的探讨暴发性Ⅰ型糖尿病(FT1DM)的发病特点,旨在提高临床医师对FT1DM的认识及诊治水平,最终改善患者的预后。方法该文收集了该科住院的2例FT1DM患者的临床特征、化验检查、诊治经过等临床资料,复习相关文献。结果病例1以腹痛、恶心、呕吐伴胰淀粉酶升高为主。病例2在产后10 d发病,伴腹痛、恶心、呕吐及转氨酶升高为主。2例患者在发病后查血糖、血酮体明显升高,胰岛功能几乎完全衰竭,但糖化血红蛋白一般正常或轻度升高,诊断为FT1DM,经积极综合治疗后症状缓解。结论暴发性Ⅰ型糖尿病(FT1DM)常急骤起病,多于1周内迅速出现酮症酸中毒,此病病情危重,诊断不及时将危及生命。因此,早期识别,及时诊断及治疗对于疾病的预后至关重要。     

Recent findings on fulminant type 1 diabetes

Fulminant type 1 diabetes (fT1D) is a new subtype of type 1 diabetes proposed by Imagawa in 2000. It is a clinical syndrome characterized by a markedly rapid and almost complete destruction of pancreatic β cells. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes. The incidence of fT1D is associated with HLA DRB1*04:05DQB1*04:01; both innate and acquired immune disorders might contribute to the development of fT1D. The presence of specific innate immune responses to enterovirus infection connected with enhanced adaptive immune pathways responsible for aggressive β cell toxicity in fT1D. The process of β cell destruction is extremely rapid in fT1D, and the insulin secretary capacity rarely recovers after the onset. The serum glycated albumin to glycated haemoglobin ratio is significantly higher in fT1D; a cut‐off value of 3.2 for serum glycated albumin to glycated haemoglobin ratio yielded 97% sensitivity and 98% specificity for differentiating fT1D from type 2 diabetes. Fulminant type 1 diabetes is associated with pregnancy. This article also updates the diagnostic criteria for fT1D by the Japanese Diabetes Association in 2012.     

Pathogenesis of fulminant type 1 diabetes

Fulminant type 1 diabetes is a new subtype of type 1 diabetes. The term was established in 2000. It is a syndrome characterized by a markedly rapid and almost complete destruction of pancreatic beta-cells. Several lines of evidence suggest that both genetic factors, such as human leukocyte antigen (HLA), and environmental factors, such as viral infection, contribute to the development of this disease. It is also suggested that autoimmune processes contribute less critically to fulminant type 1 diabetes than to classic type 1A diabetes. Based on the findings made to date, both viral infection and the subsequent immune reaction in genetically susceptible individuals cause beta-cell destruction and lead to fulminant type 1 diabetes.     

Fulminant type 1 diabetes: A comprehensive review of an autoimmune condition

Fulminant type 1 diabetes (FT1D) is a subset of type 1 diabetes characterized by extremely rapid pancreatic β‐cell destruction with aggressive progression of hyperglycaemia and ketoacidosis. It was initially classified as idiopathic type 1 diabetes due to the absence of autoimmune markers. However, subsequent studies provide evidences supporting the involvement of autoimmunity in rapid β‐cell loss in FT1D pathogenesis, which are crucial for FT1D being an autoimmune disease. This article highlights the role of immunological aspects in FT1D according to the autoimmune‐associated genetic background, viral infection, innate immunity, adaptive immunity, and pancreas histology.     

伴有急性胰腺炎的暴发性1型糖尿病1例报告及文献复习

暴发性1型糖尿病是1型糖尿病的一个少见亚型,主要特征是短时期内(多数＜7 d)急骤出现极度增高的血糖、严重的糖尿病酮症酸中毒以及水、电和酸碱平衡紊乱,病情危重凶险,发病时糖化血红蛋白A1c水平几乎正常,胰岛素自身抗体多阴性,胰岛β细胞功能完全破坏,血清C肽水平很低,治疗必须应用胰岛素.     

Type 1 diabetes in Japan

Type 1 diabetes is a multifactorial disease which results from a T-cell-mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The risk for individuals of developing type 1 diabetes varies remarkably according to country of residence and race. Japan has one of the lowest incidence rates of type 1 diabetes in the world, and recognises at least three subtypes of the condition: acute-onset (‘classical’), slow-onset, and fulminant type 1 diabetes. The incidence rate of type 1 diabetes in children aged 0–14 years in Japan increased over the period from 1973–1992, but remained constant over the last decade, averaging 2.37 cases per 100,000 persons per year; the incidence does not appear to have increased in older age groups. Although there are few reports regarding the incidence and prevalence of type 1 diabetes in adult-onset patients, it appears that the prevalence of type 1 diabetes in adults is more than twice that in childhood-onset patients and that two-thirds of them have a slow-onset form of type 1 diabetes. Differences and similarities in the association of MHC and non-MHC genes with type 1 diabetes are observed in Japan and in countries with Caucasoid populations. Highly susceptible class II HLA haplotypes identified in patients of Caucasoid origin are rarely seen in Japanese patients, whereas protective haplotypes are universal. Non-MHC genes associated with susceptibility to type 1 diabetes in both Japanese and Caucasoid patients include polymorphisms in the insulin gene, the cytotoxic T-lymphocyte antigen 4 (CTLA4) gene, the interleukin-18 (IL18) gene and the major histocompatibility complex class I chain-related gene A (MICA) gene. Fulminant type 1 diabetes is a unique subtype of type 1 diabetes that accounts for about 20% of acute-onset type 1 diabetes, and is seen mainly in adults. The challenge for the future is to investigate the underlying pathogenesis of beta cell destruction, including the genetic or environmental factors that may modify the form of onset for each subtype of Japanese type 1 diabetes.     

Fulminant type 1 diabetes--an important subtype in East Asia

Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction.     

Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes

Although pancreatic exocrine enzymes are often elevated in patients with fulminant type 1 diabetes, the onset of this elevation and its significance in disease development remain unclear. We therefore investigated the significance of elevated serum enzyme concentrations and pancreatic swelling in the development of fulminant type 1 diabetes. Serum pancreatic exocrine enzymes, including amylase, elastase-I, lipase and trypsin, were measured during the course of the disease in 11 patients with fulminant type 1 diabetes (3 men and 8 women; a range of age 24-73 years, median 33 years; a range of HbA1c at onset 4.5-6.7%, median 6.0%), all of whom developed ketotic diabetes requiring intensive insulin therapy within a month. At least one pancreatic exocrine enzyme was elevated in each patient during the course of the disease. The concentration of enzymes on admission could not be correlated with urinary excretion of C-peptide. The time course of increase in serum amylase varied in these patients. In conclusion, neither the level of serum amylase nor the swelling of pancreas was associated with the onset or severity of fulminant type 1 diabetes. The pancreatic exocrine and endocrine events may occur concomitantly but independently during the course of fulminant type 1 diabetes.