Tuomi T, Björses P, Falorni A, Partanen J, Perheentupa J, Lernmark A, Miettinen A
Department of Endocrinology, Lund University, Malmo, Sweden.
J Clin Endocrinol Metab. 1996 Apr;81(4):1488-94. doi: 10.1210/jcem.81.4.8636356.
To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1, and -DRB1 were analyzed in relation to IDDM or a decreased insulin secretory capacity. GAD65-Ab were found in six of the eight diabetic patients 0.9-8.0 yr before the onset of IDDM and in 16 (41%) nondiabetic patients during a follow-up of 2.4-19.5 yr. Eleven (28%) nondiabetic patients had GAD67-Ab and islet cell antibodies. Fasting C peptide (mean +/- SD, 0.5 +/- 0.24 vs. 1.03 +/- 0.49 nmol/L; P = 0.003) and first phase insulin response (75.6 +/- 37.9 vs. 166.4 +/- 112.7 mU/L; P = 0.019) were lower in patients with than in those without GAD65-Ab. No HLA genotype predominated in the IDDM patients or GAD65-Ab-positive nondiabetic patients, but the IDDM high risk genotypes were decreased in frequency among the patients with GAD65-Ab. In conclusion, nondiabetic autoimmune polyendocrine syndrome type 1 patients frequently have GAD65-Ab together with a decreased insulin secretory capacity, suggesting subclinical islet cell inflammation not invariably progressing to diabetes. This is not associated with HLA haplotypes conferring susceptibility to or protection from IDDM.
为评估谷氨酸脱羧酶（GAD）自身免疫与胰岛素依赖型糖尿病（IDDM）及IDDM相关人类白细胞抗原（HLA）类型之间的关联，我们研究了一组独特的47例1型自身免疫性多内分泌综合征患者，这是一种与HLA无关的隐性疾病。分析了GAD65抗体（GAD65-Ab）、GAD67-Ab、胰岛细胞抗体以及HLA-DQA1、-DQB1和-DRB1与IDDM或胰岛素分泌能力下降的关系。在8例糖尿病患者中，有6例在IDDM发病前0.9 - 8.0年检测到GAD65-Ab；在16例（41%）非糖尿病患者中，在2.4 - 19.5年的随访期间检测到GAD65-Ab。11例（28%）非糖尿病患者有GAD67-Ab和胰岛细胞抗体。有GAD65-Ab的患者空腹C肽（均值±标准差，0.5±0.24 vs. 1.03±0.49 nmol/L；P = 0.003）和第一相胰岛素反应（75.6±37.9 vs. 166.4±112.7 mU/L；P = 0.019）低于无GAD65-Ab的患者。IDDM患者或GAD65-Ab阳性非糖尿病患者中没有哪种HLA基因型占主导，但GAD65-Ab阳性患者中IDDM高危基因型的频率有所降低。总之，1型非糖尿病自身免疫性多内分泌综合征患者常伴有GAD65-Ab且胰岛素分泌能力下降，提示存在亚临床胰岛细胞炎症，但并非一定会发展为糖尿病。这与赋予IDDM易感性或保护性的HLA单倍型无关。
