Introduction: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the presence of pancreatic-autoantibodies, which are diagnostic biomarkers. The detection of autoantibodies in first-degree relatives of patients with T1D is considered a risk factor for developing the disease; however, there is little information on how long it takes from the detection of autoimmunity to the clinical onset of T1D.
Objectives: To assess the autoimmunity in first-degree relatives of patients with T1D, as well as the time to the clinical onset of diabetes and the associated risk factors.
Methods: Multicenter study of 3,430 first-degree relatives of patients with T1D collected between 1992-2018 (Parents and siblings). Pancreatic-autoantibodies (IAA, GADA, IA2A and ZnT8A) were determined by radioimmunoassay, starting the analyses at diagnosis of the proband. Qualitative variables were described as percentages and non-parametric quantitative variables as median and interquartile range (RIQ: P25-P75). Statistical analysis was carried out using univariate and multivariate logistic regression models.
Results: The prevalence of autoimmunity among relatives was 1.75% (60/3430). GADA was the most prevalent autoantibody present in 78% of the relatives, followed by IAA, ZnT8A and IA2A (42%, 23% and 13%, respectively). In particular, 65% had one autoantibody, 20% two, 8% three and 7% four. The age of autoimmunity onset was 36 years (RIQ: 11.4-44.9) for those with one autoantibody and 10 years (RIQ: 4.2-20.6) for those with multiple autoantibodies (P<0.01, Mann-Whitney-U test). Duration of follow-up 22 years (RIQ: 9.6-24.3) without differences between those who developed T1D and those who did not. Diabetes onset occurred in 40% (24/60) of cases at age 20 (RIQ: 9.7-36.7) within 5 years (RIQ: 3.8-8.4). Regarding the risk factors, the univariate analysis showed that 83% (20/24) were siblings of the proband (OR=10.0; 95%CI 2.79-35.9), 62.5% (15/24) had multiple autoantibodies (OR=8.3; 95%CI 2.50-27.80) and 75.0% (18/24) developed autoimmunity before adult age (OR=6.3; 95%CI 1.94-20.22). No significant differences were found in either the sex or the type of detected autoantibody. Multivariate analysis showed that having a sibling with T1D along with the presence of multiple autoantibodies has a high predictive value for the development of T1D (AUC-ROC=0.82; 95%CI 0.71-0.93; P=0.7, Hosmer–Lemeshow test).
Conclusions: 1. The development of autoimmunity in first-degree relatives of patients with T1D is uncommon and is associated with the clinical onset of the disease. 2. After detection of multiple autoantibodies, the siblings of patients with T1D are at high risk of developing diabetes within the first 5 years.
15 Sep 2022 - 17 Sep 2022