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型糖尿病的临床诊治

暴发性1型糖尿病是一种特发性1型糖尿病,以严重酮症酸中毒、代谢紊乱为特点。本病起病急骤、进展迅速,可出现多器官功能衰竭。患者通常病情危重,若不及时抢救,病死率很高。文章对暴发性1型糖尿病的流行病学特征、病因、诊断标准、临床症状、治疗及预后进行总结,旨在加强临床医师对该病的认识。     

暴发性1型糖尿病研究现状

暴发性1型糖尿病起病急骤,病情进展迅速,短期内胰岛β细胞几乎全部破坏,临床上常以严重的酮症酸中毒为首发症状,但糖化血红蛋白却接近正常,并叮伴有胰酶水平的升高.该病在亚洲人群中多见,其确切的发病机制尚不清楚,目前认为是遗传和环境凶素共同作用的结果.现时暴发性1型糖尿病的流行病学特点、临床及免疫学特征、发病机制、诊断标准、治疗及预后进行综述.     

暴发性1型糖尿病7例诊治分析

<正>2000年日本学者Imagawa等~[1]将一组以胰岛β细胞短时间内大量破坏,导致血糖急剧升高及酮症酸中毒等严重代谢紊乱,但缺乏糖尿病相关抗体为特征的1型糖尿病称为暴发性1型糖尿病。本研究回顾性分析暴发性1型糖尿病7例和初发经典1型糖尿病患者16例的临床病历资料,报道如下。资料与方法     

暴发性1型糖尿病八例诊治分析

暴发性1型糖尿病是一组以急骤起病、缺乏糖尿病相关抗体伴胰酶增高为特征的1型糖尿病,被归入1B型糖尿病范畴。该病超急性起病,发展快,临床表现酷似感冒和胃肠道疾病,如未及时诊断和治疗,常导致病人在短期内死亡,是内分泌代谢疾病中的急危重症。我院近年收治暴发性1型糖尿病8例,现将临床资料分析如下。     

暴发性1型糖尿病一例

1型糖尿病是以胰岛β细胞进行性破坏为特征,根据有无自身免疫反应分为1A型和1B型.暴发性1型糖尿病(fulminant type 1 diabetes)以急骤起病、胰酶升高并缺乏胰岛相关抗体为特征[1],根据美国糖尿病学会(ADA)及世界卫生组织(WHO)对糖尿病的分型诊断方案,此型被归入1B型糖尿病的范畴.该病在日本人发现较多,而中国人报道较少,其中最早的病例是一位移居日本的31岁福建籍妇女[2].现报道一例如下:     

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.     

暴发性1型糖尿病的特点与诊治

1型糖尿病包括自身免疫性(1A)和特发性(1B)两种类型.近年发现了一种发展更为迅速、病情更为严重的暴发性1型糖尿病.这类患者占酮症或酮症酸中毒起病的1型糖尿病的15%～20%.该病与HLA Ⅱ类抗原和病毒感染有一定联系.由于起病急骤,虽然患者的血糖很高,但HbA_(1C)水平几乎正常.因此凡遇到超高血糖而HbA_(1C)接近正常的酮症酸中毒患者,应考虑暴发性1型糖尿病的诊断.对该病的治疗和1型糖尿病没有区别,但因其发展迅速,抢救更应及时.     

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.     

Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan

Japan is one of the countries with lowest incidence rate of childhood type 1 diabetes in the world, averaging 2.4 cases/100,000/year. However, it appears that the prevalence of type 1 diabetes in adulthood is more than twice compared to childhood patients. There are at least three clinical subtypes of type 1 diabetes in Japan, i.e. acute-onset, slow-onset, and fulminant type 1 diabetes. 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 rare in childhood in Japan. Furthermore, the slow-onset form of type 1 diabetes might be a major subtype of disease in adulthood. In patients with acute-onset type 1 diabetes, about 90% of patients express at least one of GADAbs, IAA, and IA-2Abs at disease onset. Slow-onset form of type 1 diabetes is diagnosed as having type 2 diabetes at disease onset, which is referred as "latent autoimmune diabetes in adults (LADA)", "GADAb(+) type 2 diabetes", or "slowly progressive type 1 diabetes". The prevalence of GADAbs in adulthood patients with type 2 diabetes without insulin therapy is 3-4%, and is higher in the patients with shorter duration of diabetes. Although high levels of GADAbs are one of the predictive markers for future insulin requirement, there are a certain number of patients with high titer of GADAbs who do not progress to insulin dependency for many years, and the predictive value of GADAbs positivity for future insulin requirement is estimated about 67% by Baye's theory. Thus, accurate predictive strategies of future insulin deficiency in LADA patients using autoantibody epitope analysis, genetic determination, or T cell assay are needed for the effective immune intervention.     

Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus

Aims/hypothesis Fulminant type 1 diabetes, which is characterised by a markedly acute onset of diabetes and an absence of islet-related autoantibodies, accounts for 20% of type 1 diabetes in Japan. We aimed to clarify the contribution of the HLA subtype to fulminant type 1 diabetes in Japanese. Methods We determined the serological subtypes of HLA-A, -DR and -DQ in 115 patients with fulminant type 1 diabetes, 98 patients with typical type 1A diabetes and 190 normal control subjects. Results The frequency of HLA-DR4, but not DR9, was significantly higher in fulminant type 1 diabetes, while those of HLA-DR1, DR2, DR5 and DR8 were significantly lower than those in controls. In contrast, DR9 but not DR4 was more frequent and DR2 was extremely rare in typical type 1A diabetes. Haplotype analysis revealed that DR4-DQ4 was significantly more frequent, and both DR2-DQ1 and DR8-DQ1 were less frequent in fulminant diabetes. In type 1A diabetes, DR2-DQ1 was extremely rare while DR9-DQ3 was significantly more frequent. In the combination analysis, the homozygotes of DR4-DQ4 in fulminant type 1 diabetes and DR9-DQ3 in typical type 1A diabetes indicated high odds ratios (13.3 and 13.3, respectively). Conclusions/interpretation Our results suggest that class II HLA contributes to the development of fulminant type 1 diabetes. Susceptibility and resistance of the HLA subtype to type 1 diabetes are distinct between fulminant and typical autoimmune type 1 diabetes. An erratum to this article is available at .     

Double diabetes: possible but unpublished complication of insulin pump therapy

"Double diabetes," which refers to the coexistence of type 1 and type 2 diabetes mellitus, is a newly coined term in the diabetic literature. Excessive weight gain and a family history of type 2 diabetes in a patient with type 1 diabetes are the possible major causes. We report a case of double diabetes in a 45-year-old patient with type 1 diabetes mellitus that developed after insulin pump therapy. Insulin pump therapy is a valuable method used in the management of type 1 diabetes mellitus that may provide life comfort. However, this comfort may result in excessive weight gain, which, when combined with a family history of type 2 diabetes mellitus, may predispose to double diabetes. Clinicians must consider this pattern during the use of insulin pump therapy in patients with type 1 diabetes.     

Häufigkeit des Diabetes mellitus im Kindes- und Jugendalter in Deutschland

The incidence of type 1 diabetes in childhood and adolescence is increasing worldwide. The frequency of type 2 diabetes has also been reported to have increased primarily in ethnic minority populations (e.g. American Indians in the USA). The occurrence of type 2 diabetes among European adolescents has also been observed. This article summarises current data on the occurrence of type 1 and 2 diabetes in Germany against the background of international data. Over the past 20 years the incidence of type 1 diabetes in children and adolescents has increased continuously by 3.5%–4.5% per year in Germany. Despite the observed rise in obesity and overweight in young people, no corresponding increase in type 2 diabetes has been observed to date. Currently, the incidence of type 1 diabetes in children and adolescents in Germany is over 20 per 100,000 person-years, while that of type 2 diabetes about 1 per 100,000 person years. Thus the incidence of type 1 diabetes is approximately 20 times more frequent than that of type 2 diabetes, making it the predominant type of diabetes in Germany, as in other European countries.     

Association of fulminant type 1 diabetes with pregnancy

It has been reported that fulminant type 1 diabetes is a novel subtype of type 1B diabetes. However, whether the etiology of fulminant type 1 diabetes is associated with an autoimmune or nonautoimmune process remains to be solved. In order to further characterize fulminant type 1 diabetes, we compared the clinical, immunological and genetic characteristics with those of acute-onset type 1A diabetes. Nine patients with fulminant diabetes and nine patients with acute-onset type 1A diabetes, who had been newly diagnosed during 1998-2001, were analyzed. In female patients of child-bearing age, the onset of diabetes occurred during pregnancy or after delivery in three cases of six fulminant cases, but not in any of seven type 1A diabetes. Eight of nine fulminant patients had fever immediately prior to the onset of hyperglycemic symptoms, whereas only one of nine type 1A patients had this (P=0.002). In Japanese type 1 susceptible HLA haplotypes, DRB1*0901-DQB1*0303 was more frequent in type 1A diabetes than fulminant diabetes (7/18 vs. 0/18, P=0.004), whereas the frequency of DRB1*0405-DQB1*0401 was similar (type 1A 4/18 vs. fulminant 6/18). Therefore, pregnancy, possible viral infection, or HLADRB1*0405-DQB1*0401 may contribute to the onset of fulminant type 1 diabetes.     

Type 1 diabetes islet autoantibody markers

The diagnosis of type 1 diabetes versus other forms of diabetes such as type 2 diabetes is paramount to guiding proper therapy. Several islet autoantibodies have been identified that serve to diagnose immune-mediated, type 1a diabetes in clinically ambiguous cases. These autoantibodies also serve to predict type 1 diabetes in nondiabetic individuals. The most useful islet autoantibodies include islet cell cytoplasmic autoantibodies, insulin autoantibodies, glutamic acid decarboxylase autoantibodies, and insulinoma-associated-2 autoantibodies. Once type 1 diabetes can be safely and reliably prevented, large-scale islet autoantibody screening programs of the general pediatric population may be warranted. It is controversial whether islet autoantibodies influence the course of type 1 diabetes following diagnosis.     

Der latent autoimmune Diabetes im Erwachsenenalter (LADA): Eine Sonderform des Diabetes?

Latent autoimmune diabetes in adults (LADA) is often clinically diagnosed as a type 2 diabetes that leads however more quickly to insulin deficiency. Immunologically it is characterized by diabetes type 1-associated autoantibodies against glutamic decarboxylase (GADA) or islet cells (ICA). In Europe about 10% of type 2 diabetes patients are positive for GADA/ICA and classified therefore with LADA. This means in Germany about two times more patients with LADA exist than with type 1 diabetes. Several observations suggest interpreting LADA as a separate form of diabetes, linking both ends of the type 1 and type 2 spectrum. According the guidelines of the German Diabetes Association, LADA is allocated to type 1 diabetes, though it differs in that the insulin requirement is mostly not necessary at diagnosis, in contrast to type 1 diabetes. At the moment no evidence-based recommendations regarding therapy are available, since very few clinical studies address this point. The current therapeutic recommendation is optimization of blood glucose and concomitant risk factors, though many prefer insulin therapy due to the similarities with type 1 diabetes.     

Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment

Aims/hypothesis We have previously reported that fulminant type 1 diabetes is characterised by an absence of diabetes-related antibodies and a remarkably abrupt onset. However, little is known about the mechanism of beta cell destruction in this diabetes subtype, and to obtain insights into the aetiology of the disease, we investigated residual endocrine cells and the expression of Fas and Fas ligand in fulminant type 1 diabetes.Methods Residual beta and alpha cells were morphologically assessed in pancreatic tissue obtained by biopsy from five patients with recent-onset fulminant type 1 diabetes and five patients with recent-onset typical autoimmune type 1 diabetes. In addition, the expression of Fas and Fas ligand was evaluated by immunohistochemistry.Results In fulminant type 1 diabetes, beta and alpha cell areas were decreased significantly, compared with autoimmune type 1 diabetes and control subjects. In contrast, the alpha cell area was not decreased significantly in autoimmune type 1 diabetes, compared with that in control subjects. No Fas expression in islets and Fas ligand expression in CD3⁺ cells in the exocrine pancreas were found in the fulminant type 1 diabetic patients who underwent this evaluation.Conclusions/interpretation Our study showed that beta and alpha cells are damaged in fulminant type 1 diabetes. In addition to the lack of Fas and Fas ligand expression, the results suggest that the mechanism of beta cell destruction in fulminant type 1 diabetes is different from that in autoimmune type 1 diabetes.     

Risk of incidence of diabetes mellitus in relatives of patients with diabetes type I in retrospective questionnaire study

It is commonly known that there is a higher risk of diabetes type 1 in relatives of patients with diabetes type 1. According to some reports in families of these patients the incidence of diabetes type 2 is also higher. The aim of our study was the evaluation of incidence of diabetes type 1 and 2 in 1st and 2nd degree relatives of patients with diabetes type 1. Our study was conducted in the years 1993-2000 in the Department of Endocrinology for Children and Adolescents in Wroc?aw and in the Department of Endocrinology of Jagiellonian University in Cracow among relatives of all the patients in the age of 0-19 years with newly diagnosed diabetes type 1. Special prepared questionnaires were used in which patients were asked about: number of relatives of 1st and 2nd degree, age, sex and diagnosis of diabetes in the relatives. Data from families of 332 patients were obtained. They concerned 4080 relatives. Diabetes occurred in 121 relatives (2.96%). 20 of them were 1st degree relatives and 101--2nd degree relatives. In 31 relatives (0.76%) diabetes type 1 was diagnosed and in 88 relatives (2.16%) diabetes type 2 was diagnosed. Except for one individual (patient's mother) diabetes type 2 occurred in 2nd degree relatives. Diabetes type 1 was diagnosed in 16 1st degree relatives and 15 2nd degree relatives. They were: 1st degree relatives: 9 fathers, 3 brothers, 2 mothers and 2 sisters. 2nd degree relatives: in 8 cases siblings of patient's parents, in 7 grandparents. In families of diabetic children and adolescents relatives with type 1 and type 2 diabetes were observed, with a dominance of relatives with diabetes type 2 in 2nd degree relatives.