定义儿童期和青春期 1 型糖尿病 1 期发病风险的年龄调整基准模型。
Landmark models to define the age-adjusted risk of developing stage 1 type 1 diabetes across childhood and adolescence.
机构信息
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstr. 1, 85764, Munich-Neuherberg, Germany.
Forschergruppe Diabetes e.V. at Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany.
出版信息
BMC Med. 2019 Jul 9;17(1):125. doi: 10.1186/s12916-019-1360-3.
BACKGROUND
Autoimmune diseases are often preceded by an asymptomatic autoantibody-positive phase. In type 1 diabetes, the detection of autoantibodies to pancreatic islet antigens in genetically at-risk children is prognostic for future clinical diabetes. Testing for islet autoantibodies is, therefore, performed in a range of clinical studies. Accurate risk estimates that consider the a priori genetic risk and other risk modifiers are an important component of screening. The age of an individual is an under-appreciated risk modifier. The aim of this study was to provide age-adjusted risk estimates for the development of autoantibodies across childhood in genetically at-risk children.
METHODS
The prospective BABYDIAB and BABYDIET studies included 2441 children from birth who had a first-degree relative with type 1 diabetes. Children were born between 1989 and 2006 and were regularly followed from birth for the development of islet autoantibodies and diabetes. A landmark analysis was performed to estimate the risk of islet autoantibodies at birth and at the age 3.5, 6.5 and 12.5 years. Exponential decay curves were fitted for the risk by the age of 20 years.
RESULTS
The risk of islet autoantibodies by the age of 20 years was 8%, 4.6%, 2.6% and 0.9%, at the landmark ages of birth, 3.5, 6.5 and 12.5 years, respectively. The short-term risks (within 6 years of follow-up) at these landmark ages were 5.3%, 2.9%, 1.8% and 1%, respectively. The decline in autoantibody risk with age was modelled using a one-phase exponential decay curve (r = 0.99) with a risk half-life of 3.7 years. This risk decay model was remarkably consistent when the outcome was defined as islet autoantibody-positive or multiple islet autoantibody-positive and when the study cohort was stratified by HLA risk genotype. A similar decay model was observed for coeliac disease-associated transglutaminase antibodies in the same cohort. Unlike the risk of developing islet autoantibodies, the rate of developing clinical diabetes in children who were islet autoantibody-positive did not decline with age.
CONCLUSION
The risk of developing autoantibodies drops exponentially with age in children with a first-degree relative with type 1 diabetes.
背景
自身免疫性疾病通常先经历无症状的自身抗体阳性阶段。在 1 型糖尿病中，对遗传易感儿童的胰岛抗原自身抗体的检测对未来的临床糖尿病具有预后意义。因此，在一系列临床研究中都进行胰岛自身抗体的检测。准确的风险估计，考虑到先验遗传风险和其他风险修饰因子，是筛查的重要组成部分。个体的年龄是一个被低估的风险修饰因子。本研究的目的是为遗传易感儿童在整个儿童期提供年龄调整的自身抗体发展风险估计。
方法
前瞻性的 BABYDIAB 和 BABYDIET 研究纳入了 2441 名自出生起就有 1 型糖尿病一级亲属的儿童。这些儿童出生于 1989 年至 2006 年期间，从出生开始就定期随访，以检测胰岛自身抗体和糖尿病的发生。进行了一个里程碑分析，以估计出生时和 3.5、6.5 和 12.5 岁时胰岛自身抗体的风险。通过 20 岁时的年龄拟合了风险的指数衰减曲线。
结果
在 20 岁时，胰岛自身抗体的风险分别为出生时、3.5 岁、6.5 岁和 12.5 岁时的 8%、4.6%、2.6%和 0.9%。在这些里程碑年龄的短期风险（随访 6 年内）分别为 5.3%、2.9%、1.8%和 1%。使用单阶段指数衰减曲线（r=0.99）对年龄相关的自身抗体风险下降进行建模，风险半衰期为 3.7 年。当结局定义为胰岛自身抗体阳性或多种胰岛自身抗体阳性，以及根据 HLA 风险基因型对研究队列进行分层时，该风险衰减模型非常一致。在同一队列中，也观察到了与乳糜泻相关的转谷氨酰胺酶抗体的类似衰减模型。与胰岛自身抗体发生的风险不同，在胰岛自身抗体阳性的儿童中，临床糖尿病的发病速度并没有随年龄的增长而下降。
结论
在一级亲属患有 1 型糖尿病的儿童中，自身抗体的发生风险随年龄呈指数下降。
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