Decochez K, De Leeuw I H, Keymeulen B, Mathieu C, Rottiers R, Weets I, Vandemeulebroucke E, Truyen I, Kaufman L, Schuit F C, Pipeleers D G, Gorus F K
Diabetes Research Centre, Free University of Brussels, Belgium.
Diabetologia. 2002 Dec;45(12):1658-66. doi: 10.1007/s00125-002-0949-8. Epub 2002 Nov 12.
AIMS/HYPOTHESIS: Multiple islet autoantibody positivity is currently believed to best predict progression to Type I (insulin-dependent) diabetes mellitus. We compared its predictive value with that of positivity for a particular type of islet autoantibody, directed against the IA-2 antigen.
Autoantibodies against islet cell cytoplasm (ICA), insulin (IAA), GAD (GADA) and IA-2 (IA-2A) were measured at initial sampling in 1724 non-diabetic siblings (median age [range]:16 [0-39] years) of Type I diabetic patients with a median follow-up of 50 months.
On initial sampling 11% of siblings were positive for one antibody type or more and 2.1% for three of more types. During follow-up, 27 antibody-positive siblings developed diabetes. Using survival analysis, the risk for clinical onset within 5 years was 34% in subjects positive for three or more types compared with 13% in those with one type or more. Progression to diabetes amounted to 12% within 5 years among siblings positive for IAA, 20% for ICA, 19% for GADA but 59% for IA-2A (p<0.001 vs absence of the respective antibody). IA-2A were detected in 1.7% of all siblings and in 56% of the prediabetic subjects on first sampling. Initial positivity for two or three antibody markers was associated with a higher progression rate in IA-2A positive as compared to IA-2A negative siblings (p=0.001). In absence of IA-2A initial positivity for another antibody (IAA, ICA or GADA) conferred a low (<10% within 5 years) risk of diabetes compared to subjects lacking this antibody.
CONCLUSIONS/INTERPRETATION: In siblings of Type I diabetic patients, IA-2A positivity is a more direct predictor of impending clinical onset than multiple antibody positivity per se. Assessment of IA-2A status allows us to select subjects with homogeneously high risk of diabetes for participation in prevention trials.
目的/假设：目前认为多种胰岛自身抗体阳性最能预测进展为I型（胰岛素依赖型）糖尿病。我们将其预测价值与针对IA-2抗原的特定类型胰岛自身抗体阳性的预测价值进行了比较。
对1724名I型糖尿病患者的非糖尿病同胞（中位年龄[范围]：16[0 - 39]岁）进行初始采样时检测胰岛细胞胞浆自身抗体（ICA）、胰岛素自身抗体（IAA）、谷氨酸脱羧酶自身抗体（GADA）和IA-2自身抗体（IA-2A），中位随访时间为50个月。
在初始采样时，11%的同胞有一种或多种抗体阳性，2.1%有三种或更多种抗体阳性。在随访期间，27名抗体阳性的同胞患了糖尿病。采用生存分析，三种或更多种抗体阳性的受试者5年内临床发病风险为34%，而一种或更多种抗体阳性的受试者为13%。IAA阳性的同胞5年内糖尿病进展率为12%，ICA为20%，GADA为19%，但IA-2A为59%（与相应抗体阴性相比，p<0.001）。首次采样时，所有同胞中1.7%检测到IA-2A，糖尿病前期受试者中56%检测到IA-2A。与IA-2A阴性的同胞相比，IA-2A阳性的同胞中两种或三种抗体标志物初始阳性与更高的进展率相关（p = 0.001）。在没有IA-2A的情况下，与缺乏该抗体的受试者相比，另一种抗体（IAA、ICA或GADA）初始阳性的糖尿病风险较低（5年内<10%）。
结论/解读：在I型糖尿病患者的同胞中，IA-2A阳性比多种抗体阳性本身更能直接预测即将发生的临床发病。评估IA-2A状态使我们能够选择糖尿病风险均一性高的受试者参与预防试验。
