title: Islet autoantibody development during follow-up of high-risk children from the general Norwegian population from three months of age: design and early results from the MIDIA study.
abstract: We describe the design of the MIDIA study and present serial islet autoantibody data from 3 months of age in the 526 first enrolled children from the general population carrying the type 1 diabetes high-risk HLA-DRB1*0401-DQA1*03-DQB1*0302/DRB1*0301-DQA1*05-DQB1*02 genotype. Blood samples were obtained from children at ages 3, 6, 9 and 12 months and annually thereafter to a median age of 12 months. Autoantibodies to insulin, glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured with radiobinding assays. About 25,000 general population newborns were genotyped, and among 526 children with the high-risk HLA genotype, 2104 samples were assayed. Fourteen children were positive in at least two consecutive samples, including 12 who were positive for > or =2 autoantibodies at least once, of which five developed type 1 diabetes at median age 15.3 months. Seven of 14 persistently positive children seroconverted before 9 months, including two before 6 months of age. The estimated cumulative probability of multiple autoantibody positivity at 5 years was 7.3% (95% confidence interval: 3.5-12.4%). Thus, persistent islet autoimmunity is not uncommon in the first year of life in children from the general population carrying the high-risk HLA genotype, and may develop as early as at 6 months of age.
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, NO-0403 Oslo, Norway. lars.christian.stene@fhi.no
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.forename: Elisabet
authors.initials: E
authors.lastname: Witsø
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Trond
authors.initials: T
authors.lastname: Rasmussen
authors.forename: Per
authors.initials: P
authors.lastname: Magnus
authors.forename: Ondrej
authors.initials: O
authors.lastname: Cinek
authors.forename: Turid
authors.initials: T
authors.lastname: Wetlesen
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D009664:Norway; D012306:Risk
chemical_list: D001323:Autoantibodies; D006681:HLA-D Antigens