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1型糖尿病和成人隐匿性自身免疫性糖尿病——两个不同年龄组糖尿病患者中HLA-DRB1 *03和DRB1 *04等位基因的出现情况

Type 1 diabetes and LADA--occurrence of HLA-DRB1 *03 and DRB1 *04 alleles in two age different groups of diabetics.

作者信息

Weber P, Meluzínová H, Kubesová H, Ambrosová P, Polcarová V, Cejkova P, Cerna M

机构信息

Department of Internal Medicine, Geriatrics and Practical Medicine, Faculty Hospital and Masaryk University, Brno, Czech Republic.

出版信息

Adv Gerontol. 2010;23(2):243-8.

Abstract

Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) are connected with autoimmune insulitis (associated with islet cell autoantibodies) and the specific high-risk HLA class II genotype. The study was aimed at analyzing time and clinical characteristics of the diabetics with an onset of the disease after 35 y. (T1D and LADA). Main target of the study was to assess possible role of the old age onset and compare it with diabetics with the onset in the middle age (incl. analyzing HLA-DRB1 genotype). In the study, we included 103 diabetics with an onset of autoimmune diabetes at 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. 46 men and 57 women of the average age 65.7 +/- 13.8 y. (range 35-93 y.) were out of this number. 41 were assessed as the T1D patients and 61 as the LADA ones. As a control group we used 99 healthy individuals. Patients of the T1D subgroup developed diabetes in the age of 50.8 +/- 15.1 y. and of the LADA subgroup in the age of 52.6 +/- 12.8 y. Its duration in the time of this study was 10.7 +/- 11.6 y.; respectively 5.3 +/- 7.1 y. Fasting and postprandial C-peptide levels were statistically higher (p < 0.01) in the LADA subgroup vs. T1D. Obesity 1st and 2nd grade were present together only in 12.6%. BMI was not statistically significantly different between both groups. We found in our diabetic patients the predisposition alleles HLA-DRB103, HLA-DRB104 and particularly their combination. The occurrence of these HLA alleles is significantly higher in T1D patients in comparison to control groups (p = 0.01, OR = 4.0). In our study, the occurrence of the susceptible HLA-DRB103 and HLA-DRB104 alleles in T1D patients is higher than in LADA. The presence of these alleles identifies patients of high risk and requirement of insulin therapy. Since risk alleles are similarly present in middle and old age, environmental factors probably play similar role in these onsets of autoimmune diabetes.

摘要

成年期发病的1型糖尿病(T1D)和成人迟发性自身免疫性糖尿病(LADA)与自身免疫性胰岛炎(与胰岛细胞自身抗体相关)以及特定的高危HLA II类基因型有关。该研究旨在分析35岁以后发病的糖尿病患者(T1D和LADA)的发病时间和临床特征。该研究的主要目的是评估老年发病的可能作用,并将其与中年发病的糖尿病患者进行比较(包括分析HLA-DRB1基因型)。在该研究中,我们纳入了103例35岁及以上发病的自身免疫性糖尿病患者,这些患者均已住院治疗,随后在糖尿病门诊进行长期观察。其中有46名男性和57名女性,平均年龄为65.7±13.8岁(范围为35 - 93岁)。其中41例被评估为T1D患者,61例为LADA患者。我们将99名健康个体作为对照组。T1D亚组患者的糖尿病发病年龄为50.8±15.1岁,LADA亚组患者的发病年龄为52.6±12.8岁。在本研究期间,其病程分别为10.7±11.6年和5.3±7.1年。LADA亚组的空腹和餐后C肽水平在统计学上高于T1D亚组(p < 0.01)。1级和2级肥胖仅共存在12.6%的患者中。两组之间的BMI在统计学上无显著差异。我们在糖尿病患者中发现了HLA-DRB103、HLA-DRB104等位基因易感性,尤其是它们的组合。与对照组相比,这些HLA等位基因在T1D患者中的发生率显著更高(p = 0.01,OR = 4.0)。在我们的研究中,T1D患者中易感性HLA-DRB103和HLA-DRB1于LADA患者。这些等位基因的存在可识别高危患者以及胰岛素治疗的需求。由于风险等位基因在中年和老年患者中同样存在,环境因素可能在这些自身免疫性糖尿病的发病中起类似作用。

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