title: Circulating IGF1 and IGFBP3 in relation to the development of β-cell autoimmunity in young children.
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.
authors.affiliation: 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.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Peet
authors.affiliation: 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.
authors.forename: Anu-Maaria
authors.initials: AM
authors.lastname: Hämäläinen
authors.affiliation: 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.
authors.forename: Pille
authors.initials: P
authors.lastname: Kool
authors.affiliation: 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.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: 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
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: 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.
authors.forename: Vallo
authors.initials: V
authors.lastname: Tillmann
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000276:immunology / Q000378:metabolism*; D008297:Male
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I