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.
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.
Stene
Lars C
LC
Division of Epidemiology, Norwegian Institute of Public Health, NO-0403 Oslo, Norway. lars.christian.stene@fhi.no
Witsø
Elisabet
E
Torjesen
Peter A
PA
Rasmussen
Trond
T
Magnus
Per
P
Cinek
Ondrej
O
Wetlesen
Turid
T
Rønningen
Kjersti S
KS
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
D001323:Autoantibodies; D006681:HLA-D Antigens