Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies - An 8-year follow-up of the Washington State Diabetes Prediction Study
Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies - An 8-year follow-up of the Washington State Diabetes Prediction Study
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DOI：
10.2337/diacare.25.3.505
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发表时间：
2002-03-01
期刊：
影响因子：
16.2
通讯作者：
Monks, S
中科院分区：
文献类型：
--
作者：
LaGasse, JM;Palmer, JP;Monks, S
目的：几乎90%的1型糖尿病患者没有密切的家族史。在一项针对普通人群的长期前瞻性研究中，我们试图评估当前最佳的预测策略，即多种定义的自身抗体。研究设计和方法：对4.505名华盛顿学龄儿童进行胰岛自身抗体（胰岛细胞抗体[ICAs]）和针对人GAD IA2/ICA512和胰岛素的定义自身抗体（d-aab）检测。8年后，我们重新联系了3000名（67%）受试者，其中97%的受试者在任何测试中都达到了第99百分位。结果：6名受试者发展为糖尿病（中位间隔2.8年），全部来自12名患有多种d-aab的个体，代表50%的阳性预测值（95% CI 25-75%）和100%的敏感性（58-100%）。其中，6例d-aab合并ICA的患者中有0例发生糖尿病，26例仅发生ICA的患者中有0例发生糖尿病，7例d-aab等于第99百分位的患者中有0例发生糖尿病，另1例d-aab等于第975百分位的患者中有0例发生糖尿病，86例d-aab患者中有0例发生糖尿病，2863例无d-aab或ICA的患者中有0例发生糖尿病。校正验证偏倚后，多个d-aab的特异性为99.9%（99.86-99.93%）。在这个年龄，新的d-aab很少出现。一旦出现，d-aab通常与疾病进展无关，尽管胰岛素自身抗体的情况较差。顺序葡萄糖耐量试验显示，4名多重d-aab受试者的胰岛素分泌正常，未发生糖尿病。在患有糖尿病的儿童中，如果HLA-DQ基因分型先于抗体检测，那么六分之五（83%）的儿童将被纳入糖尿病，但即使与其他遗传标记一起考虑，HLA-DQ也不能解释高风险受试者的结果。结论：在14岁时建立了多个d-aab，并前瞻性地确定了8年内发生1型糖尿病的所有学龄儿童。
OBJECTIVE - Almost 90% of type 1 diabetes appears in individuals without a close family history. We sought to evaluate the best current predictive strategy, multiple defined autoantibodies, in a long-term prospective study in the general population.RESEARCH DESIGN AND METHODS - Autoantibodies to pancreatic islets (islet cell antibodies [ICAs]) and defined autoantibodies (d-aab) to human GAD IA2/ICA512, and insulin were tested in 4.505 Washington school children. Eight years later, 3,000 (67%) subjects were recontacted, including 97% of subjects with any test >99th percentile.RESULTS - Six subjects developed diabetes (median interval 2.8 years), all from among the 12 individuals with multiple d-aab, representing 50% positive predictive value (95% CI 25-75%) and 100% sensitivity (58-100%). Among the others, diabetes occurred in 0 of 6 with one d-aab plus ICA, 0 of 26 with ICA only, 0 of 7 with one d-aab equaling the 99th percentile and another d-aab equaling the 97.5th percentile, 0 of 86 with one d-aab, and 0 of 2,863 with no d-aab or ICA. Adjusted for verification bias, multiple d-aab were 99.9% specific (99.86-99.93%). At this age, new d-aab seldom appeared. Once present, d-aab usually persisted regardless of disease progression, although less so for insulin autoantibodies. Insulin secretion by sequential glucose tolerance testing remained normal in four multiple d-aab subjects not developing diabetes. Of children developing diabetes, five of six (83%) would be included if HLA-DQ genotyping preceded antibody testing, but HLA-DQ did not explain outcomes among high-risk subjects, even when considered along with other genetic markers.CONCLUSIONS - Multiple d-aab were established by age 14 years and prospectively identified all school children who developed type 1 diabetes within 8 years.