Diabetes Care. 2019 Feb;42(2):192-199. doi: 10.2337/dc18-0288. Epub 2018 Jul 30.
There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.
Subjects from the TrialNet Pathway to Prevention Study ( = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.
At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects.
Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
在双胞胎中的一个被诊断为患有胰岛自身抗体和 1 型糖尿病后，对于两个个体发生进展至胰岛自身抗体阳性和 1 型糖尿病的一致性风险，存在可变的报告。我们研究了同卵双胞胎、非同卵双胞胎和全同胞中胰岛自身抗体阳性、1 型糖尿病的发展以及遗传因素和共同环境对自身抗体阳性的影响。
2004 年至 2015 年，来自 TrialNet 预防研究途径（=48026 例）的受试者被筛选为胰岛自身抗体（谷氨酸脱羧酶抗体[GADA]、胰岛素瘤相关抗原 2 [IA-2A]和胰岛素自身抗体[IAA]）。在这些受试者中，17226 例（157 对同卵双胞胎、283 对非同卵双胞胎和 16786 对全同胞）随访了自身抗体阳性或 1 型糖尿病的中位数为 2.1 年。
在筛查时，同卵双胞胎比非同卵双胞胎或全同胞更有可能出现阳性 GADA、IA-2A 和 IAA（均<0.0001）。年龄较小、男性和遗传因素是 IA-2A、IAA、一种或多种自身抗体阳性和两种或多种自身抗体阳性表达的重要因素（均≤0.03）。最初自身抗体阳性的同卵双胞胎在 3 年内患糖尿病的风险为 69%，而最初自身抗体阴性的同卵双胞胎为 1.5%。在非同卵双胞胎中，最初多个自身抗体阳性的个体在 3 年内发生 1 型糖尿病的风险为 72%，最初单个自身抗体阳性的个体为 13%，最初自身抗体阴性的个体为 0%。全同胞在 3 年内发生 1 型糖尿病的风险分别为多个自身抗体阳性的个体为 47%、单个自身抗体阳性的个体为 12%和最初自身抗体阴性的个体为 0.5%。
最初多个和单个自身抗体阳性的同卵双胞胎以及多个自身抗体阳性的非同卵双胞胎在 3 年内发生 1 型糖尿病的风险较高。遗传易感性、年龄和男性是双胞胎发生自身抗体阳性的重要危险因素。
