Achenbach P, Warncke K, Reiter J, Williams A J K, Ziegler A G, Bingley P J, Bonifacio E
Diabetes Research Institute, Koelner Platz 1, Munich, Germany.
Diabetologia. 2006 Dec;49(12):2969-76. doi: 10.1007/s00125-006-0451-9. Epub 2006 Sep 26.
AIMS/HYPOTHESIS: Combinations of autoantibody characteristics, including antibody number, titre, subclass and epitope have been shown to stratify type 1 diabetes risk in islet autoantibody-positive relatives. The aim of this study was to determine whether autoantibody characteristics change over time, the nature of such changes, and their implications for the development of diabetes.
Five-hundred and thirteen follow-up samples from 141 islet autoantibody-positive first-degree relatives were tested for islet autoantibody titre, IgG subclass, and GAD and IA-2 antibody epitope. All samples were categorised according to four risk stratification models. Relatives had a median follow-up of 6.8 years and 48 developed diabetes during follow-up. Survival analysis was used to determine the probability of change in risk category and of progression to diabetes.
For each stratification model, the majority of relatives (71-81%) remained in the same risk category throughout follow-up. In the remainder, changes occurred both from lower to higher and from higher to lower risk categories. For all four models, relatives aged < 15 years were more likely to change risk category than those aged >15 years (0.001 < p < 0.03). Relatives whose autoantibody status changed from low- to high-risk categories had a higher risk of diabetes than relatives who remained in low-risk categories, and inclusion of autoantibody status during follow-up improved diabetes risk stratification in Cox proportional hazards models (p < 0.001).
CONCLUSIONS/INTERPRETATION: Changes in islet autoantibodies are relevant to pathogenesis, and are likely to signal alterations in the disease process. Detection of changes through follow-up measurement will improve diabetes risk stratification, particularly in young individuals.
目的/假设：自身抗体特征的组合，包括抗体数量、滴度、亚类和表位，已被证明可对胰岛自身抗体阳性亲属的1型糖尿病风险进行分层。本研究的目的是确定自身抗体特征是否随时间变化、这种变化的性质及其对糖尿病发展的影响。
对141名胰岛自身抗体阳性的一级亲属的513份随访样本进行胰岛自身抗体滴度、IgG亚类、谷氨酸脱羧酶（GAD）和胰岛抗原2（IA-2）抗体表位检测。所有样本均根据四种风险分层模型进行分类。亲属的中位随访时间为6.8年，随访期间48人患糖尿病。生存分析用于确定风险类别变化和糖尿病进展的概率。
对于每种分层模型，大多数亲属（71%-81%）在整个随访期间风险类别保持不变。其余亲属中，既有从低风险类别变为高风险类别，也有从高风险类别变为低风险类别的情况。对于所有四种模型，年龄<15岁的亲属比年龄>15岁的亲属更有可能改变风险类别（0.001<p<0.03）。自身抗体状态从低风险类别变为高风险类别的亲属患糖尿病的风险高于仍处于低风险类别的亲属，在Cox比例风险模型中纳入随访期间的自身抗体状态可改善糖尿病风险分层（p<0.001）。
结论/解读：胰岛自身抗体的变化与发病机制相关，可能预示疾病进程的改变。通过随访测量检测变化将改善糖尿病风险分层，尤其是在年轻人中。
