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[成人隐匿性自身免疫性糖尿病(LADA):自身免疫性起源的1型糖尿病临床谱的一部分]

[Latent autoimmune diabetes in adults(LADA): part of the clinical spectrum of type-1 diabetes mellitus of autoimmune origin].

作者信息

Pánczél P, Hosszúfalusi N, Bornemisza B, Horváth L, Jánoskuti L, Füst G, Rajczy K, Vatay A, Prohászka Z, Madácsy L, Luczay A, Blatniczky L, Halmos T, Körner A, Szilvási I, Romics L

机构信息

Semmelweis Egyetem, Altalálnos Orvostudományi Kar, III. Belgyógyászati Klinika.

出版信息

Orv Hetil. 2001 Nov 18;142(46):2571-8.

PMID:11770176
Abstract

According to the most recent classification of diabetes mellitus the latent autoimmune diabetes in adults belongs to the group of type 1 autoimmune diabetes mellitus, as a slowly progressive form. It is not clear whether LADA is a distinct clinical entity or it is a part of the clinical spectrum of type 1 diabetes mellitus. The authors compare the antropologic (body mass index, waist to hip ratio), immunologic (occurrence of islet cell cytoplasmic autoantibodies and autoantibodies against glutamic acid decarboxylase and tyrosin phosphatase), genetic (HLA DR and DQ alleles known to be associated to type 1 diabetes mellitus) characteristics and occurrence of the features of the metabolic syndrome in the groups of type 1 and type 2 diabetes and LADA. 81 type 1 and 190 type 2 diabetics and 38 LADA patients were involved into the study. Freshly diagnosed type 1 diabetics served for controls of the autoantibody study: 48 patients manifested < or = 16 years of age and 89 type 1 diabetics manifested above 16 years of age. The three main diabetic groups differed in age: the average age in the type 1, type 2 and LADA groups were 37, 63 and 58 years respectively. There was no difference among the three groups in gender. The duration of the disease differed significantly between the type 2 and LADA groups (4.0 and 8.0 years respectively). In spite of the shorter duration of the disease in the LADA group, compared to the type 2 diabetics the frequency of insulin dependency was significantly higher in the LADA (81.6%) than in the type 2 group (46.7%). The BMI and WHR were comparable between the type 1 and LADA patients (average values were 23 and 0.83 in type 1 patients and 23.25 and 0.89 in LADA). The type 2 group differed significantly from type 1 and LADA (average values were 29.1 and 0.5). The concentration of glycated hemoglobin was comparable in the three groups. But there was a significant difference in HbA1c concentration between the freshly diagnosed subgroups of type 1 and LADA patients: 10.85% and 8% respectively. The fasting C-peptid levels were significantly higher in the sera of type 2 diabetics (0.75 pmol/l) compared to type 1 (0.2 pmol/l) and LADA patients (0.29 pmol/l). There was a significant difference in C-peptid concentrations between the type 1 and LADA groups, too. The insulin deficiency in LADA seemed to be not as severe as in type 1 diabetes. The serum total cholesterol and triglyceride levels were significantly higher and the HDL cholesterol concentration significantly lower in type 2 diabetics comparing to type 1 and LADA patients and there was no significant difference in this respect between the type 1 and LADA groups. The frequency of occurrence of hypertension differed no significantly between type 2 and LADA, but that of in type 1 diabetes was significantly lower than both type 2 and LADA. The occurrence of multiple autoantibodies (ICA + GADA + anti-IA2) was much more frequent in type 1 diabetes compared to LADA. In the sera of LADA patients the occurrence of ICA and GADA alone or ICA + GADA was characteristic (31.5% - 21.1% - 15.8% respectively). There was no difference between type 1 diabetes and LADA in the occurrence of the alleles of the MHC kown to be associated with type 1 diabetes. The occurrence of the haplotypes HLA DQ2/DR3 and/or DQ8/DR4 was observed in two thirds of type 1 diabetic and LADA patients. Chronic diabetic complications were observed in all of the groups and there was only a secondary connection of the complications with the type of the diabetes. Based on the results the authors suggest that LADA is a part of the clinical spectrum of type 1 diabetes of autoimmune origin.

摘要

根据最新的糖尿病分类,成人隐匿性自身免疫性糖尿病属于1型自身免疫性糖尿病组,是一种缓慢进展的形式。目前尚不清楚成人隐匿性自身免疫性糖尿病(LADA)是一种独特的临床实体,还是1型糖尿病临床谱的一部分。作者比较了1型糖尿病、2型糖尿病和LADA组的人类学特征(体重指数、腰臀比)、免疫学特征(胰岛细胞质自身抗体以及抗谷氨酸脱羧酶和酪氨酸磷酸酶自身抗体的出现情况)、遗传学特征(已知与1型糖尿病相关的HLA DR和DQ等位基因)以及代谢综合征特征的出现情况。该研究纳入了81例1型糖尿病患者、190例2型糖尿病患者和38例LADA患者。新诊断的1型糖尿病患者用作自身抗体研究的对照:48例患者年龄≤16岁,89例1型糖尿病患者年龄大于16岁。三个主要糖尿病组的年龄有所不同:1型、2型和LADA组的平均年龄分别为37岁、63岁和58岁。三组之间的性别无差异。2型糖尿病组和LADA组的病程差异显著(分别为4.0年和8.0年)。尽管LADA组的病程较2型糖尿病组短,但LADA组胰岛素依赖的频率(81.6%)显著高于2型糖尿病组(46.7%)。1型糖尿病患者和LADA患者的体重指数(BMI)和腰臀比(WHR)相当(1型糖尿病患者的平均值分别为23和0.83,LADA患者为23.25和0.89)。2型糖尿病组与1型糖尿病组和LADA组有显著差异(平均值分别为29.1和0.5)。三组糖化血红蛋白的浓度相当。但新诊断的1型糖尿病患者亚组和LADA患者亚组之间的糖化血红蛋白A1c(HbA1c)浓度存在显著差异:分别为10.85%和8%。2型糖尿病患者血清中的空腹C肽水平(0.75 pmol/l)显著高于1型糖尿病患者(0.2 pmol/l)和LADA患者(0.29 pmol/l)。1型糖尿病组和LADA组之间的C肽浓度也存在显著差异。LADA患者的胰岛素缺乏似乎不如1型糖尿病严重。与1型糖尿病患者和LADA患者相比,2型糖尿病患者的血清总胆固醇和甘油三酯水平显著更高,高密度脂蛋白胆固醇浓度显著更低,1型糖尿病组和LADA组在这方面无显著差异。2型糖尿病和LADA中高血压的发生频率差异不显著,但1型糖尿病中的高血压发生频率显著低于2型糖尿病和LADA。与LADA相比,1型糖尿病中多种自身抗体(胰岛细胞抗体[ICA]+谷氨酸脱羧酶抗体[GADA]+抗胰岛细胞抗原2抗体[anti-IA2])的出现频率更高。在LADA患者血清中,单独出现ICA和GADA或ICA+GADA具有特征性(分别为31.5% - 21.1% - 15.8%)。已知与1型糖尿病相关的主要组织相容性复合体(MHC)等位基因的出现情况在1型糖尿病和LADA之间无差异。三分之二的1型糖尿病患者和LADA患者出现了单倍型HLA DQ2/DR3和/或DQ8/DR4。所有组均观察到慢性糖尿病并发症,且并发症与糖尿病类型仅存在次要关联。基于这些结果,作者认为LADA是自身免疫性起源的1型糖尿病临床谱的一部分。

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