Biobizkaia Health Research Institute, Barakaldo, Spain.
UPV/EHU, CIBERDEM, CIBERER, Endo-ERN, Barakaldo, Spain.
Front Endocrinol (Lausanne). 2024 Aug 12;15:1411686. doi: 10.3389/fendo.2024.1411686. eCollection 2024.
The detection of pancreatic autoantibodies in first-degree relatives of patients with type 1 diabetes (T1D) is considered a risk factor for disease. Novel available immunotherapies to delay T1D progression highlight the importance of identifying individuals at risk who might benefit from emerging treatments. The objective was to assess the autoimmunity in first-degree relatives of patients with T1D, estimate the time from autoimmunity detection to the onset of clinical diabetes, and identify the associated risk factors.
Retrospective multicenter study of 3,015 first-degree relatives of patients with T1D recruited between 1992 and 2018. Pancreatic autoantibodies (IAA, GADA, IA2A, and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. All those with positive autoimmunity and normal fasting blood glucose without clinical symptoms of diabetes were followed up in the study. The progression rate to T1D was assessed according to sex, relationship with the proband, age at autoimmunity detection, type/number of autoantibodies, and HLA-DRB1 genotype. Cox proportional-hazard models and Kaplan-Meier survival plots were used for statistical analyses.
Among the relatives, 21 progenitors [43.7 years (IQR: 38.1-47.7)] and 27 siblings [7.6 years (IQR: 5.8-16.1)] had positive autoantibodies. Of these, 54.2% (95% CI: 39.2%-68.6%) developed T1D (age at autoimmunity detection 11 months to 39 years) in a median of 5 years (IQR: 3.6-8.7; ranged from 0.9 to 22.6 years). Risk factors associated with faster progression to T1D were multiple autoimmunity and <20 years at autoimmunity detection. Younger relatives (<20 years) with multiple autoantibodies had a 5-year cumulative risk of developing diabetes of 52.9% (95% CI: 22.1%-71.6%) and a 20-year risk of 91.2% (95% CI: 50.5%-98.4%). The 20-year risk decreased to 59.9% (95% CI: 21.9%-79.5%) if only one risk factor was met and to 35.7% (95% CI: 0.0%-66.2%) if the relative was older than 20 years with one autoantibody.
In first-degree relatives with autoimmunity, the time to progression to T1D is faster in children and adolescents with multiple autoantibodies. Young adults are also at risk, which supports their consideration in screening strategies for people at risk of developing T1D.
在 1 型糖尿病（T1D）患者的一级亲属中检测到胰腺自身抗体被认为是疾病的一个危险因素。新型免疫疗法延迟 T1D 进展凸显了识别可能受益于新兴治疗方法的高危人群的重要性。本研究的目的是评估 T1D 患者一级亲属的自身免疫情况，估计从自身免疫检测到临床糖尿病发病的时间，并确定相关的危险因素。
这是一项回顾性多中心研究，纳入了 1992 年至 2018 年间招募的 3015 名 T1D 患者的一级亲属。通过放射免疫分析测定胰腺自身抗体（IAA、GADA、IA2A 和 ZnT8A），从先证者诊断时开始分析。所有自身抗体阳性且空腹血糖正常、无糖尿病临床症状的患者均纳入本研究进行随访。根据性别、与先证者的关系、自身免疫检测时的年龄、自身抗体的类型/数量和 HLA-DRB1 基因型评估向 T1D 的进展率。采用 Cox 比例风险模型和 Kaplan-Meier 生存图进行统计学分析。
在亲属中，21 名后代（43.7 岁（IQR：38.1-47.7））和 27 名兄弟姐妹（7.6 岁（IQR：5.8-16.1））自身抗体阳性。其中，54.2%（95%CI：39.2%-68.6%）在中位 5 年（IQR：3.6-8.7；范围 0.9-22.6 年）内发展为 T1D（自身免疫检测时的年龄为 11 个月至 39 岁）。与更快进展为 T1D 相关的危险因素是多种自身抗体和<20 岁时的自身免疫检测。<20 岁且有多种自身抗体的年轻亲属，5 年累积患糖尿病的风险为 52.9%（95%CI：22.1%-71.6%），20 年风险为 91.2%（95%CI：50.5%-98.4%）。如果只有一个危险因素，则 20 年的风险降至 59.9%（95%CI：21.9%-79.5%），如果亲属年龄大于 20 岁且只有一种自身抗体，则风险降至 35.7%（95%CI：0.0%-66.2%）。
在有自身免疫的一级亲属中，具有多种自身抗体的儿童和青少年向 T1D 进展的时间更快。年轻成年人也存在风险，这支持在 T1D 高危人群的筛查策略中考虑他们。
