Endocrinology Department, Complejo Hospitalario Universitario Insular-Materno Infantil, de Gran Canaria, Spain.
Diabetes Metab Res Rev. 2011 Jul;27(5):493-8. doi: 10.1002/dmrr.1189.
Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAIDs) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAIDs in the Type 1 Diabetes Genetics Consortium data set.
Three thousand two hundred and sixty-three families with at least two siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD (glutamic acid decarboxylase) and anti-protein tyrosine phosphatase (IA-2) were measured and human leukocyte antigen (HLA) genotyping was performed. Siblings with T1D with and without AAIDs were compared and a multivariate regression analysis was performed to find predictors of AAIDs. T1D-associated HLA haplotypes were defined as the four most susceptible and protective, respectively.
One or more AAIDs were present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, there was a female predominance and more family history of AAIDs in the group with AAIDs, as well as more frequent anti-GAD and less frequent anti-IA-2 antibodies. Risk and protective HLA haplotype distributions were similar, though DRB10301-DQA10501-DQB1*0201 was more frequent in the group with AAIDs. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAIDs.
In patients with T1D, the presence of AAIDs is associated with female predominance, more frequent family history of AAIDs, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved.
1 型糖尿病（T1D）是一种临床表现异质性的疾病。伴发自身免疫性疾病（AAIDs）可能代表一种独特形式的自身免疫性糖尿病，涉及特定的发病机制。本研究旨在探讨 1 型糖尿病遗传学联盟（Type 1 Diabetes Genetics Consortium，T1DGC）数据集AAIDs 的预测因子。
共纳入 3263 个至少有 2 个 T1D 同胞的家系。采用问卷调查收集临床资料，检测谷氨酸脱羧酶（glutamic acid decarboxylase，GAD）抗体和蛋白酪氨酸磷酸酶（protein tyrosine phosphatase，IA-2）抗体，进行人类白细胞抗原（human leukocyte antigen，HLA）基因分型。比较 T1D 同胞中伴发和不伴发 AAIDs 的患者，采用多变量回归分析寻找 AAIDs 的预测因子。将 T1D 相关 HLA 单倍型定义为最易感和最保护的前 4 个单倍型。
14.4%的 T1D 同胞伴发一种或多种 AAIDs。伴发 AAIDs 的患者年龄、当前年龄和诊断后时间更长，女性占比更高，有 AAIDs 家族史的患者更多，GAD 抗体阳性率更高，IA-2 抗体阳性率更低。风险和保护 HLA 单倍型分布相似，但伴发 AAIDs 的患者 DRB10301-DQA10501-DQB1*0201 单倍型更常见。多变量分析显示，女性、起病年龄、AAIDs 家族史、诊断后时间和 GAD 抗体阳性与 AAIDs 相关。
在 T1D 患者中，AAIDs 与女性占比更高、AAIDs 家族史更常见、T1D 发病年龄较晚、GAD 抗体阳性率更高有关，尽管这些患者的疾病病程较长。某些 HLA 单倍型占优势提示可能涉及特定的发病机制。
