Desai M, Cull C A, Horton V A, Christie M R, Bonifacio E, Lampasona V, Bingley P J, Levy J C, Mackay I R, Zimmet P, Holman R R, Clark A
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Diabetologia. 2007 Oct;50(10):2052-60. doi: 10.1007/s00125-007-0745-6. Epub 2007 Jul 27.
AIMS/HYPOTHESIS: Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs) in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease progression or insulin requirement.
GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by the requirement for intensified glucose-lowering therapy.
GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65 in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up period, nor any association between epitope reactivity and insulin requirement.
CONCLUSIONS/INTERPRETATION: GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.
目的/假设：成人隐匿性自身免疫性糖尿病（LADA）是一种自身免疫性糖尿病的缓慢进展形式，在无需立即进行胰岛素治疗的老年患者中会出现胰岛蛋白自身抗体。其临床病程的标志物尚不明确。本研究的目的是确定参与英国前瞻性糖尿病研究（UKPDS）的LADA患者中，谷氨酸脱羧酶65自身抗体（GADA）的持续存在或变化是否与疾病进展或胰岛素需求相关。
对242例诊断时GADA阳性的UKPDS患者测定GADA水平及其对人GAD65 N端、中间和C端区域的相对表位反应性；使用放射结合测定法检测随访0.5年、3年和6年后采集的样本。将GADA状态与临床细节以及通过强化降糖治疗需求评估的疾病进展进行比较。
GADA水平在0.5年至6年之间波动，但242例患者中有225例持续存在。未观察到GADA水平与疾病进展或胰岛素需求之间的关联。超过70%的患者抗体反应针对GAD65的C端和中间表位处，针对N端的不到9%。在6年随访期内表位反应模式无变化，表位反应性与胰岛素需求之间也无关联。
结论/解读：LADA诊断后GADA持续存在6年，但水平及对不同GAD65表位的反应性与疾病进展无关。
