Positivity for islet autoantibodies is used for diagnosis of type 1 diabetes. However, the importance of the autoantibody level at diagnosis of type 1 diabetes is not clear. Here, we assessed the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) autoantibody levels, measured using radiobinding assays, on genetic and clinical characteristics at diagnosis of 1536 participants with diabetes who were positive for these autoantibodies. We show that GADA and IA-2A levels had bimodal distributions, but ZnT8A level did not. The comparison of genetic and clinical characteristics between high and low level categories showed high GADA level was associated with older age at diagnosis, female sex and HLA-DR3-DQ2, whereas high IA-2A level was associated with younger age of diagnosis, ZnT8A positivity and HLA-DR4-DQ8. We replicated our findings in an independent cohort of 427 people with type 1 diabetes where autoantibodies were measured using enzyme-linked immunosorbent assays. In conclusion, Islet autoantibody levels provide additional information over positivity in type 1 diabetes at diagnosis. The bimodality of islet autoantibody levels highlights the novel aspect of heterogeneity of type 1 diabetes which may have implications on prediction, treatment and prognosis.

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1型糖尿病胰岛自身抗体水平分布及其与遗传和临床特征的关系

胰岛自身抗体阳性用于诊断 1 型糖尿病。然而，自身抗体水平在 1 型糖尿病诊断中的重要性尚不清楚。在这里，我们评估了谷氨酸脱羧酶 (GADA)、胰岛抗原 2 (IA-2A) 和锌转运蛋白 8 (ZnT8A) 自身抗体水平（使用放射性结合测定法测量）与 1536 名糖尿病参与者诊断时的遗传和临床特征之间的关联。这些自身抗体呈阳性。我们表明 GADA 和 IA-2A 水平具有双峰分布，但 ZnT8A 水平没有。高水平和低水平类别之间遗传和临床特征的比较表明，高 GADA 水平与诊断时年龄较大、女性和HLA-DR3-DQ2 相关，而高 IA-2A 水平与较年轻的诊断年龄、ZnT8A 阳性和HLA-DR4-DQ8 相关。我们在 427 名 1 型糖尿病患者的独立队列中重复了我们的发现，其中使用酶联免疫吸附试验测量了自身抗体。总之，胰岛自身抗体水平提供了超过 1 型糖尿病诊断时阳性的额外信息。胰岛自身抗体水平的双峰突出了 1 型糖尿病异质性的新方面，这可能对预测、治疗和预后产生影响。