Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Endocrinology of the First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Diabetes Metab Res Rev. 2021 Jan;37(1):e3357. doi: 10.1002/dmrr.3357. Epub 2020 Jun 21.
The aim of this study was to investigate differences in clinical features and HLA genotypes between adult-onset and childhood-onset patients with type 1 diabetes in a Chinese population.
This study enrolled 716 Han Chinese patients with type 1 diabetes from Guangdong (258 childhood-onset and 458 adult-onset) to compare their clinical features. Of them 214 patients with classical type 1 diabetes (100 childhood-onset and 114 adult-onset) were selected for HLA DR and DQ genotyping by next-generation sequencing.
Adult-onset patients were characterized by longer duration of symptoms before diagnosis, lower frequency of DKA at disease onset, less frequent autoantibody positivity, higher serum C-peptide concentrations, and better glycemic control. These findings were replicated in the restricted cohort of 214 patients with classical type 1 diabetes. Compared with childhood-onset patients, adult-onset patients had a lower frequency of the DR9 haplotype, as well as lower frequency of high-risk DR3/DR4 and DR3/DR9 genotypes, but higher frequency of DR3/DR3 genotype and DR3/X, DR4/X or DR9/X (X, non-risk) genotypes.
Adult-onset type 1 diabetic patients with susceptible haplotypes (DR3, DR4 or DR9) were more likely to carry protective DR-DQ haplotypes than childhood-onset patients, which suggested the association between less risk DR-DQ genotypes and the less severe clinical manifestation in adult-onset patients.
本研究旨在探讨中国汉族人群中成人起病和儿童起病 1 型糖尿病患者的临床特征和 HLA 基因型差异。
本研究纳入了 716 例汉族 1 型糖尿病患者（广东地区，258 例儿童起病，458 例成人起病），比较其临床特征。其中 214 例经典 1 型糖尿病患者（100 例儿童起病，114 例成人起病）采用下一代测序进行 HLA-DR 和 DQ 基因分型。
成人起病患者的诊断前症状持续时间较长，发病时酮症酸中毒发生率较低，自身抗体阳性率较低，血清 C 肽浓度较高，血糖控制较好。这些发现也在 214 例经典 1 型糖尿病患者的限定队列中得到了验证。与儿童起病患者相比，成人起病患者 DR9 单倍型频率较低，高危 DR3/DR4 和 DR3/DR9 基因型频率较低，但 DR3/DR3 基因型和 DR3/X、DR4/X 或 DR9/X（X，非风险）基因型频率较高。
携带易感单倍型（DR3、DR4 或 DR9）的成人起病 1 型糖尿病患者比儿童起病患者更有可能携带保护性 DR-DQ 单倍型，这表明在成人起病患者中，DR-DQ 基因型风险较低与临床症状较轻之间存在关联。
