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, Hunan, China.
Diabetes Metab Res Rev. 2023 Sep;39(6):e3676. doi: 10.1002/dmrr.3676. Epub 2023 Jun 20.
Idiopathic type 1 diabetes (T1D) is a neglected subtype of T1D. Our aim was to investigate the frequency, clinical characteristics, and human leucocyte antigen (HLA) genotypes of idiopathic T1D.
We enrolled 1205 newly diagnosed T1D patients in our analysis. To exclude monogenic diabetes in autoantibody-negative patients, we utilised a custom monogenic diabetes gene panel. Individuals negative for autoantibodies and subsequently excluded for monogenic diabetes were diagnosed with idiopathic T1D. We collected clinical characteristics, measured islet autoantibodies by radioligand assay and obtained HLA data.
After excluding 11 patients with monogenic diabetes, 284 cases were diagnosed with idiopathic T1D, accounting for 23.8% (284/1194) of all newly diagnosed T1D cases. When compared with autoimmune T1D, idiopathic T1D patients showed an older onset age, higher body mass index among adults, lower haemoglobin A1c, higher levels of fasting C-peptide and 2-h postprandial C-peptide, and were likely to have type 2 diabetes (T2D) family history and carry 0 susceptible HLA haplotype (all p < 0.01). A lower proportion of individuals carrying 2 susceptible HLA haplotypes in idiopathic T1D was observed in the adult-onset subgroup (15.7% vs. 38.0% in child-onset subgroup, p < 0.001) and in subgroup with preserved beta-cell function (11.0% vs. 30.1% in subgroup with poor beta-cell function, p < 0.001). Multivariable correlation analyses indicated that being overweight, having T2D family history and lacking susceptible HLA haplotypes were associated with negative autoantibodies.
Idiopathic T1D represents about 1/4 of newly diagnosed T1D, with adult-onset and preserved beta-cell function patients showing lower HLA susceptibility and more insulin resistance.
特发性 1 型糖尿病（T1D）是 T1D 的一个被忽视的亚型。本研究旨在探讨特发性 T1D 的频率、临床特征和人类白细胞抗原（HLA）基因型。
我们纳入了 1205 例新诊断的 T1D 患者进行分析。为了排除自身抗体阴性患者中的单基因糖尿病，我们使用了定制的单基因糖尿病基因panel。自身抗体阴性且随后排除单基因糖尿病的患者被诊断为特发性 T1D。我们收集了临床特征，通过放射配体测定法测量胰岛自身抗体，并获得了 HLA 数据。
排除 11 例单基因糖尿病患者后，284 例被诊断为特发性 T1D，占所有新诊断 T1D 病例的 23.8%（284/1194）。与自身免疫性 T1D 相比，特发性 T1D 患者的发病年龄较大，成年患者的体重指数较高，血红蛋白 A1c 水平较低，空腹 C 肽和餐后 2 小时 C 肽水平较高，且更有可能有 2 型糖尿病（T2D）家族史，并携带 0 个易感 HLA 单倍型（均 p<0.01）。在成年起病亚组和β细胞功能保存亚组中，特发性 T1D 患者携带 2 个易感 HLA 单倍型的比例较低（分别为 15.7%和 38.0%，p<0.001；11.0%和 30.1%，p<0.001）。多变量相关分析表明，超重、有 T2D 家族史和缺乏易感 HLA 单倍型与阴性自身抗体有关。
特发性 T1D 约占新诊断 T1D 的 1/4，成年起病和β细胞功能保存患者的 HLA 易感性较低，胰岛素抵抗更为明显。
