Abstract：
This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies\' association with clinical characteristics and HLA-DR-DQ genes.
This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.
IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.
IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.
IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.
IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.
摘要：
目的：本研究调查了1型糖尿病（T1D）和隐匿性自身免疫性糖尿病（LAD）患者胰岛素瘤相关2自身抗体（IA-2A）和锌转运体8自身抗体（ZnT8A）的分布以及自身抗体与临床特征和HLA-DR-DQ基因的相关性。
方法：这项横断面研究招募了来自中国46家医院的17,536名糖尿病患者。共有189例T1D患者和58例IA-2A阳性的LAD患者，126例T1D患者和86例LAD患者的ZnT8A阳性，并选择231例2型糖尿病（T2D）患者进行胰岛自身抗体评估，临床表型，HLA-DR-DQ基因频率。
结果：IA-2A在T1D和LAD患者中呈双峰分布。低IA-2A滴度LAD患者的空腹C肽（FCP）较低（p<0.01），较低的餐后C肽（PCP）（p<0.001），与T2D患者相比，血红蛋白A1c（HbA1c）水平更高（p<0.05）。IA-2A滴度高的LAD患者比IA-2A滴度低的LAD患者年轻(p<0.05)。低IA-2A滴度T1D患者FCP较低(p<0.01),PCP降低（p<0.01），HbA1c水平高于高IA-2A滴度LAD患者（p<0.05）。HLA-DR-DQ遗传分析表明，IA-2A阳性患者的易感HLA单倍型频率高于T2D患者（p<0.001）。具有高ZnT8A滴度LAD的患者具有较低的FCP(p=0.045),下PCP（p=0.023），与低ZnT8A滴度LAD患者相比，更高的HbA1c水平（p=0.009）和更高的总易感单倍型频率（p<0.001）。
结论：IA-2A在T1D和LAD患者中呈双峰分布，IA-2A的存在可以证明LAD的部分临床特征。ZnT8A滴度对LAD患者胰岛功能有一定的预测价值。
方法：这项横断面研究招募了来自中国46家医院的17,536名糖尿病患者。共有189例T1D患者和58例IA-2A阳性的LAD患者，126例T1D患者和86例LAD患者的ZnT8A阳性，并选择231例2型糖尿病（T2D）患者进行胰岛自身抗体评估，临床表型，HLA-DR-DQ基因频率。
结果：IA-2A在T1D和LAD患者中呈双峰分布。低IA-2A滴度LAD患者的空腹C肽（FCP）较低（p<0.01），较低的餐后C肽（PCP）（p<0.001），与T2D患者相比，血红蛋白A1c（HbA1c）水平更高（p<0.05）。IA-2A滴度高的LAD患者比IA-2A滴度低的LAD患者年轻(p<0.05)。低IA-2A滴度T1D患者FCP较低(p<0.01),PCP降低（p<0.01），HbA1c水平高于高IA-2A滴度LAD患者（p<0.05）。HLA-DR-DQ遗传分析表明，IA-2A阳性患者的易感HLA单倍型频率高于T2D患者（p<0.001）。具有高ZnT8A滴度LAD的患者具有较低的FCP(p=0.045),下PCP（p=0.023），与低ZnT8A滴度LAD患者相比，更高的HbA1c水平（p=0.009）和更高的总易感单倍型频率（p<0.001）。
结论：IA-2A在T1D和LAD患者中呈双峰分布，IA-2A的存在可以证明LAD的部分临床特征。ZnT8A滴度对LAD患者胰岛功能有一定的预测价值。
