Aleksandr Peet1, Anu-Maaria Hämäläinen2, Pille Kool2, Jorma Ilonen3, Mikael Knip4, Vallo Tillmann3. 1. 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 aleksandr.peet@kliinikum.ee. 2. 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. 3. 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. 4. 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 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
Abstract
OBJECTIVE: This study aimed at investigating the role of IGF1 and IGF binding protein 3 (IGFBP3) in the development of β-cell autoimmunity. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: This study aimed at investigating the role of IGF1 and IGF binding protein 3 (IGFBP3) in the development of β-cell autoimmunity. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Melanie R Shapiro; Clive H Wasserfall; Sean M McGrail; Amanda L Posgai; Rhonda Bacher; Andrew Muir; Michael J Haller; Desmond A Schatz; Johnna D Wesley; Matthias von Herrath; William A Hagopian; Cate Speake; Mark A Atkinson; Todd M Brusko Journal: Diabetes Date: 2019-12-11 Impact factor: 9.461