Dittler J, Seidel D, Schenker M, Ziegler A G
Third Medical Department, Hospital München-Schwabing, and Diabetes Research Institute, Munich, Germany.
Diabetes. 1998 Apr;47(4):592-7. doi: 10.2337/diabetes.47.4.592.
A new radiobinding assay for the simultaneous detection of antibodies to GAD and the tyrosine phosphatase IA2 has been recently described in patients with newly diagnosed type 1 diabetes. Here we assessed sensitivity and predictive value of this GADIA2-combi test in first-degree relatives of type 1 diabetic patients compared with islet cell antibody (ICA) and insulin autoantibody (IAA) screening. Of 1,606 relatives, 77 (4.8%) had elevated GADIA2-combi titers above the 99th percentile of 105 nondiabetic control subjects, and results were confirmed by testing these samples for GAD antibody (GADA) and tyrosine phosphatase IA2 antibody (IA2A) in the single antibody test (29 GADA+/IA2A+, 44 GADA+/IA2A-, and 4 IA2A+/GADA-). A further 9 of 1,606 relatives had detectable ICA (1) or IAA (8), but they were negative in the GADIA2-combi assay as well as in the single test for GADA or IA2A. Twenty-four relatives progressed to IDDM within a median follow-up time of 5.6 years (range 0.5-8.2). The sensitivity of antibody determination in relatives with progression to IDDM was 92% for the GADIA2-combi assay, 96% for the combined testing of IAA and GADIA2-combi antibodies, and 83, 67, 67, and 79%, respectively, for GADA, IA2A, IAA, or ICA testing alone. The cumulative life-table risk of antibody-positive relatives was related to GADIA2-combi titers (5-year risk: >50 U, 51% [95% CI 30-73]; >10 to 50 U, 12% [1-24]; <10 U, 0.17% [0-0.5]; P=0.0001) and on the presence of IA2A in addition to GADA (5-year risk: GADA+/IA2A+, 47% [25-68]; GADA+/IA2A-, 15% [2-28]; P=0.006). In those with detectable antibodies, risk was not associated with age (<15 vs. >15 years) or relation to proband (offspring, sibling, parent). Relatives with GADIA2-combi antibodies >10 U and the additional presence of IAA had a slightly higher diabetes risk than relatives without IAA (5-year: IAA+, 46% [23-68]; IAA-, 19% [6-32]; P=0.07). Furthermore, low first-phase insulin release after intravenous glucose tolerance test was associated with risk in relatives with GADIA2-combi antibodies (P=0.01). These results indicate that the GADIA2-combi test is a valuable marker for first-line screening and risk assessment of type 1 diabetes in relatives. It can be used for venous as well as capillary blood samples.
最近在新诊断的1型糖尿病患者中描述了一种用于同时检测谷氨酸脱羧酶（GAD）抗体和酪氨酸磷酸酶IA2抗体的新型放射结合测定法。在此，我们评估了与胰岛细胞抗体（ICA）和胰岛素自身抗体（IAA）筛查相比，这种GADIA2联合检测在1型糖尿病患者一级亲属中的敏感性和预测价值。在1606名亲属中，77名（4.8%）的GADIA2联合检测滴度高于105名非糖尿病对照受试者的第99百分位数，通过对这些样本进行GAD抗体（GADA）和酪氨酸磷酸酶IA2抗体（IA2A）的单项检测来确认结果（29名GADA+/IA2A+，44名GADA+/IA2A-，4名IA2A+/GADA-）。在1606名亲属中，另有9名可检测到ICA（1名）或IAA（8名），但他们在GADIA2联合检测以及GADA或IA2A的单项检测中均为阴性。24名亲属在中位随访时间5.6年（范围0.5 - 8.2年）内进展为胰岛素依赖型糖尿病（IDDM）。进展为IDDM的亲属中，抗体测定的敏感性在GADIA2联合检测中为92%，在IAA和GADIA2联合抗体的联合检测中为96%，而单独进行GADA、IA2A、IAA或ICA检测时分别为83%、67%、67%和79%。抗体阳性亲属的累积生命表风险与GADIA2联合检测滴度相关（5年风险：>50 U，51%[95%可信区间30 - 73]；>10至50 U，12%[1 - 24]；<10 U，0.17%[0 - 0.5]；P = 0.0001），并且除GADA外还存在IA2A时也相关（5年风险：GADA+/IA2A+，47%[25 - 68]；GADA+/IA2A-，15%[2 - 28]；P = 0.006）。在可检测到抗体的人群中，风险与年龄（<15岁与>15岁）或与先证者的关系（后代、兄弟姐妹、父母）无关。GADIA2联合抗体>10 U且另外存在IAA的亲属比无IAA的亲属患糖尿病的风险略高（5年：IAA+，46%[23 - 68]；IAA-，19%[6 - 32]；P = 0.07）。此外，静脉葡萄糖耐量试验后低的第一相胰岛素释放与GADIA2联合抗体阳性的亲属的风险相关（P = 0.01）。这些结果表明，GADIA2联合检测是1型糖尿病亲属一线筛查和风险评估的有价值标志物。它可用于静脉血和毛细血管血样本。
