Institute of Diabetes Research, Helmholtz Center Munich, Neuherberg, Germany.
J Autoimmun. 2011 Aug;37(1):3-7. doi: 10.1016/j.jaut.2011.02.004. Epub 2011 Mar 3.
The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year period in children genetically predisposed to type 1 diabetes. Between 1989 and 2010, children who were first-degree relatives of patients with type 1 diabetes and who were born in Germany were prospectively followed from birth without intervention. A total of 324 children (BABYDIAB study) born between 1989 and 2000 and 216 children (TEDDY study) born between 2004 and 2010 with matched HLA genotypes were recruited before age 3 months and included for analysis. Children were followed for the development of autoantibodies to insulin, GAD, and IA-2, and for progression to diabetes. The cumulative frequency of diabetes by age 4 years was 2.5% (95% CI 0.8-4.2%) in BABYDIAB children and 6.2% (95% CI 2.3-10.1%) in TEDDY children (p = 0.03). The cumulative frequency of islet autoantibodies by age 4 years was similar in the children from both studies (11.3% vs 13.9%). Progression to diabetes from the development of islet autoantibodies was markedly increased in autoantibody-positive children from the more recently recruited TEDDY cohort (50% progression within 85.2 months for BABYDIAB children vs 9.6 months for TEDDY children; p = 0.009), also if children were further selected on the basis of high-risk HLA genotypes or the development of autoantibodies to multiple islet antigens (p = 0.01). The findings suggest that recent increasing incidence of type 1 diabetes in young children could be due to weakening of mechanisms that normally regulate autoimmune destruction of islet beta cells.
1 型糖尿病的发病率在全球范围内呈上升趋势，尤其在儿童中更为明显。由于 1 型糖尿病发生之前存在胰岛抗原自身免疫，因此儿童中胰岛自身免疫的发生率必然会增加，或者一旦发生胰岛自身免疫，糖尿病的进展速度就会更快。本研究旨在确定在具有 1 型糖尿病遗传易感性的儿童中，胰岛自身免疫的发生率或从自身免疫进展到糖尿病发病的速度是否在 20 年期间发生了变化。1989 年至 2010 年期间，对来自 1 型糖尿病患者一级亲属且出生于德国的儿童进行前瞻性随访，且不进行任何干预。共有 324 名（BABYDIAB 研究）于 1989 年至 2000 年期间出生和 216 名（TEDDY 研究）于 2004 年至 2010 年期间出生的具有匹配 HLA 基因型的儿童在 3 个月龄之前被招募并纳入分析。儿童接受胰岛素、GAD 和 IA-2 自身抗体的发展以及进展为糖尿病的监测。BABYDIAB 儿童中 4 岁时糖尿病的累积频率为 2.5%（95%CI，0.8-4.2%），TEDDY 儿童中为 6.2%（95%CI，2.3-10.1%）（p=0.03）。在这两项研究中，4 岁时胰岛自身抗体的累积频率相似（11.3%vs13.9%）。在最近招募的 TEDDY 队列中自身抗体阳性的儿童中，从胰岛自身抗体发展到糖尿病的进展明显增加（BABYDIAB 儿童中 85.2 个月内的进展率为 50%，而 TEDDY 儿童为 9.6 个月；p=0.009），如果基于高危 HLA 基因型或对多种胰岛抗原的自身抗体的发展进一步选择儿童，这种情况更为明显（p=0.01）。研究结果表明，近期儿童 1 型糖尿病发病率的上升可能是由于调节胰岛β细胞自身免疫破坏的机制减弱所致。
