Department of PediatricsUniversity of Tartu, N. Lunini 6 51014 Tartu, EstoniaChildren's Clinic of Tartu University HospitalN. Lunini 6, Tartu, EstoniaChildren's Hospital and Jorvi HospitalUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandImmunogenetics LaboratoryUniversity of Turku, Turku, FinlandDepartment of Clinical MicrobiologyUniversity of Eastern Finland, Kuopio, FinlandDiabetes and Obesity Research ProgramUniversity of Helsinki, Helsinki, FinlandFolkhälsan Research CenterHelsinki, Finland andDepartment of PediatricsTampere University Hospital, Tampere, Finland Department of PediatricsUniversity of Tartu, N. Lunini 6 51014 Tartu, EstoniaChildren's Clinic of Tartu University HospitalN. Lunini 6, Tartu, EstoniaChildren's Hospital and Jorvi HospitalUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandImmunogenetics LaboratoryUniversity of Turku, Turku, FinlandDepartment of Clinical MicrobiologyUniversity of Eastern Finland, Kuopio, FinlandDiabetes and Obesity Research ProgramUniversity of Helsinki, Helsinki, FinlandFolkhälsan Research CenterHelsinki, Finland andDepartment of PediatricsTampere University Hospital, Tampere, Finland
Department of PediatricsUniversity of Tartu, N. Lunini 6 51014 Tartu, EstoniaChildren's Clinic of Tartu University HospitalN. Lunini 6, Tartu, EstoniaChildren's Hospital and Jorvi HospitalUniversity of Helsinki and Helsinki University Central Hospital, Helsinki, FinlandImmunogenetics LaboratoryUniversity of Turku, Turku, FinlandDepartment of Clinical MicrobiologyUniversity of Eastern Finland, Kuopio, FinlandDiabetes and Obesity Research ProgramUniversity of Helsinki, Helsinki, FinlandFolkhälsan Research CenterHelsinki, Finland andDepartment of PediatricsTampere University Hospital, Tampere, Finland.
Eur J Endocrinol. 2015 Aug;173(2):129-37. doi: 10.1530/EJE-14-1078. Epub 2015 May 6.
This study aimed at investigating the role of IGF1 and IGF binding protein 3 (IGFBP3) in the development of β-cell autoimmunity.
Five hundred and sixty-three subjects with HLA-conferred susceptibility to type 1 diabetes (T1D) were monitored for signs of seroconversion to positivity for insulin and/or GAD, IA2, and zinc transporter 8 autoantibodies by the age of 3 years. In 40 subjects who developed at least one autoantibody, IGF1 and IGFBP3 plasma concentrations were measured and compared with 80 control subjects who remained negative for autoantibodies, and were matched for age, sex, country of origin, and HLA genotype. The increments of IGF1, IGFBP3, and IGF1/IGFBP3 molar ratio before and after seroconverison were compared with corresponding time intervals in controls.
The IGF1 concentrations at the age of 12 months and the IGF1/IGFBP3 ratio at the age of 24 months were lower in the autoantibody-positive children (P<0.05). The increase in circulating IGFBP3 was significantly higher in the autoantibody-positive children before seroconversion than in the corresponding time intervals in controls (0.43 mg/l; 95% CI 0.29-0.56 vs 0.22 mg/l; 95% CI 0.10-0.34 mg/l; P<0.01). Children carrying the high-risk HLA genotype had lower plasma IGF1 and IGFBP3 concentrations at the age of 24 months than those with low-risk genotypes (P<0.05 and < 0.01 respectively).
Circulating IGF1 and IGFBP3 appear to have a role in early development of β-cell autoimmunity. The decreased IGF1 concentrations in children with the high-risk HLA genotype may contribute to the reduced growth previously described in such children.
本研究旨在探讨胰岛素样生长因子 1（IGF1）和胰岛素样生长因子结合蛋白 3（IGFBP3）在β细胞自身免疫发展中的作用。
对 563 名具有 1 型糖尿病（T1D）易感性的 HLA 个体进行监测，观察其在 3 岁时是否出现胰岛素和/或谷氨酸脱羧酶（GAD）、IA2 和锌转运蛋白 8 自身抗体阳性的血清转化迹象。在 40 名至少出现一种自身抗体的受试者中，测量 IGF1 和 IGFBP3 血浆浓度，并与 80 名仍保持自身抗体阴性的对照受试者进行比较，这些对照受试者在年龄、性别、原籍国和 HLA 基因型方面相匹配。比较自身抗体阳性儿童与对照儿童在血清转化前后 IGF1、IGFBP3 和 IGF1/IGFBP3 摩尔比的增量。
自身抗体阳性儿童在 12 个月龄时的 IGF1 浓度和 24 个月龄时的 IGF1/IGFBP3 比值较低（P<0.05）。在自身抗体阳性儿童血清转化前，循环 IGFBP3 的增加明显高于对照组相应时间间隔（0.43mg/l；95%CI 0.29-0.56 vs 0.22mg/l；95%CI 0.10-0.34mg/l；P<0.01）。携带高危 HLA 基因型的儿童在 24 个月龄时的血浆 IGF1 和 IGFBP3 浓度低于低危基因型的儿童（P<0.05 和<0.01）。
循环 IGF1 和 IGFBP3 似乎在β细胞自身免疫的早期发展中发挥作用。高危 HLA 基因型儿童 IGF1 浓度降低可能导致此前描述的此类儿童生长受限。
