National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
J Clin Endocrinol Metab. 2022 Jan 1;107(1):e293-e302. doi: 10.1210/clinem/dgab589.
Partial remission (PR) is a specific stage in type 1 diabetes (T1D). Although human leukocyte antigen (HLA) class II loci are the strongest genetic determinants in T1D, the relationship between PR and HLA remains unclear.
To investigate the association between PR status and HLA genotypes in patients with T1D.
A total of 237 patients with T1D were included. PR was defined according to C-peptide ≥300 pmol/L. The frequency of PR and peak C-peptide levels during remission phase were compared according to HLA status. Clinical characteristics including age of onset and diabetes autoantibodies were collected. All analyses were duplicated when subjects were divided into childhood- and adult-onset T1D.
The median follow-up time was 24 months, 65.8% (156/237) of patients with T1D went into PR. DR9/DR9 carriers had a lower PR rate (44.2% vs 70.6%, P = .001) and were less likely to enter PR (OR = 0.218, 95% CI 0.098-0.487, P < .001) than the non-DR9/DR9 carriers, observed in both childhood- and adult-onset T1D. Besides, the peak C-peptide level during PR phase was also lower in DR9/DR9 carriers, and more notable in adult-onset T1D. When compared with non-DR9/DR9 carriers, T1D with DR9/DR9 genotype presented an older age of onset and a lower positivity of zinc transporter 8 antibody (ZnT8A), and the lower trend of ZnT8A was only found in adult-onset T1D (P = .049).
Patients with T1D carrying susceptible DR9/DR9 are less prone to undergo PR. Additionally, the recovery extent of β-cell function during the PR phase tends to be lower in adults carrying DR9/DR9, which might be associated with ZnT8A.
部分缓解（PR）是 1 型糖尿病（T1D）的一个特定阶段。尽管人类白细胞抗原（HLA）Ⅱ类基因座是 T1D 最强的遗传决定因素，但 PR 与 HLA 之间的关系仍不清楚。
探讨 T1D 患者 PR 状态与 HLA 基因型的关系。
共纳入 237 例 T1D 患者。根据 C 肽≥300 pmol/L 定义 PR。根据 HLA 状态比较 PR 患者和缓解期峰值 C 肽水平的频率。收集包括发病年龄和糖尿病自身抗体在内的临床特征。当将受试者分为儿童和成人发病 T1D 时，所有分析均进行了重复。
中位随访时间为 24 个月，237 例 T1D 患者中有 65.8%（156/237）进入 PR。DR9/DR9 携带者 PR 率较低（44.2%比 70.6%，P=0.001），更不易进入 PR（OR=0.218，95%CI 0.098-0.487，P<0.001），这在儿童和成人发病 T1D 中均观察到。此外，DR9/DR9 携带者在 PR 期的 C 肽峰值也较低，在成人发病 T1D 中更为显著。与非 DR9/DR9 携带者相比，携带 DR9/DR9 基因型的 T1D 发病年龄较大，锌转运体 8 抗体（ZnT8A）阳性率较低，且仅在成人发病 T1D 中 ZnT8A 的趋势较低（P=0.049）。
携带易感 DR9/DR9 的 T1D 患者更不易发生 PR。此外，在携带 DR9/DR9 的成年人中，PR 期间β细胞功能的恢复程度往往较低，这可能与 ZnT8A 有关。
