Yu L, Gianani R, Eisenbarth G S
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver 80262.
Diabetes. 1994 Oct;43(10):1229-33. doi: 10.2337/diab.43.10.1229.
In this study, we demonstrate that levels of glutamic acid decarboxylase (GAD) autoantibodies (GAAs) by radioassay differ between relatives with GAD-absorbable and GAD-nonabsorbable islet cell antibodies (ICAs). Extremely high levels of GAAs are often found in relatives with GAD-absorbable ICAs (> 1,800 cpm, > 9 SD above normal control subjects; mean = 1,991 cpm), and lower levels (mean = 1,078 cpm) of GAAs were present in relatives with nonabsorbable ICAs (P < 10(-5). The serum levels of GAAs were remarkably constant for relatives of both groups over time. The levels of GAAs were found to be inversely related to both the levels of insulin autoantibodies and the rate of loss of intravenous glucose-stimulated insulin secretion (P < 10(-5) and P < 0.01, respectively). Relatives with low positive levels of GAAs had more rapid loss of insulin secretion and were at high risk to become diabetic (50% diabetic at 4 years) compared with relatives with higher levels (1,800 cpm) of GAAs (10% diabetic at 4 years; P < 0.05). These data suggest that high levels of GAAs are associated with a decreased risk of progression to type I diabetes and extend the hypothesis that distinct subsets of ICAs and GAAs with differing prognostic significance can be identified.
在本研究中，我们证明，通过放射测定法检测的谷氨酸脱羧酶（GAD）自身抗体（GAA）水平在具有GAD可吸收性和GAD不可吸收性胰岛细胞抗体（ICA）的亲属之间存在差异。GAD可吸收性ICA的亲属中经常发现极高水平的GAA（>1800 cpm，比正常对照受试者高>9个标准差；平均值=1991 cpm），而不可吸收性ICA的亲属中GAA水平较低（平均值=1078 cpm）（P<10⁻⁵）。两组亲属的血清GAA水平随时间推移相当稳定。发现GAA水平与胰岛素自身抗体水平以及静脉注射葡萄糖刺激的胰岛素分泌丧失率均呈负相关（分别为P<10⁻⁵和P<0.01）。与GAA水平较高（1800 cpm）的亲属相比，GAA阳性水平较低的亲属胰岛素分泌丧失更快，患糖尿病的风险更高（4年时50%患糖尿病）（4年时10%患糖尿病；P<0.05）。这些数据表明，高水平的GAA与I型糖尿病进展风险降低相关，并扩展了这样一种假设，即可以识别出具有不同预后意义的不同亚组的ICA和GAA。
