title: HbA1c Predicts Time to Diagnosis of Type 1 Diabetes in Children at Risk.
abstract: Prediction of type 1 diabetes is based on the detection of multiple islet autoantibodies in subjects who are at increased genetic risk. Prediction of the timing of diagnosis is challenging, however. We assessed the utility of HbA1c levels in predicting the clinical disease in genetically predisposed children with multiple autoantibodies. Cord blood samples from 168,055 newborn infants were screened for class II HLA genotypes in Finland, and 14,876 children with increased genetic risk for type 1 diabetes were invited to participate in regular follow-ups, including screening for diabetes-associated autoantibodies. When two or more autoantibodies were detected, HbA1c levels were analyzed at each visit. During follow-up, multiple (two or more) autoantibodies developed in 466 children; type 1 diabetes was diagnosed in 201 of these children (43%, progressors), while 265 children remained disease free (nonprogressors) by December 2011. A 10% increase in HbA1c levels in samples obtained 3-12 months apart predicted the diagnosis of clinical disease (hazard ratio [HR] 5.7 [95% CI 4.1-7.9]) after a median time of 1.1 years (interquartile range [IQR] 0.6-3.1 years) from the observed rise of HbA1c. If the HbA1c level was ≥5.9% (41 mmol/mol) in two consecutive samples, the median time to diagnosis was 0.9 years (IQR 0.3-1.5, HR 11.9 [95% CI 8.8-16.0]). In conclusion, HbA1c is a useful biochemical marker when predicting the time to diagnosis of type 1 diabetes in children with multiple autoantibodies.
authors.affiliation: Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Department of General Practice, University of Tampere, Tampere, Finland Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Aspholm
authors.affiliation: Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Tytti
authors.initials: T
authors.lastname: Pokka
authors.affiliation: Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Milla-Riikka
authors.initials: MR
authors.lastname: Hautakangas
authors.affiliation: Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Nora
authors.initials: N
authors.lastname: Haatanen
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lempainen
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: Department of Pediatrics, Tampere University Hospital, Tampere, Finland Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Department of Pediatrics, Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland riitta.veijola@oulu.fi.
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
mesh_terms: D001323:Autoantibodies / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005312:Fetal Blood; D005387:Finland / Q000453:epidemiology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
chemical_list: D001323:Autoantibodies; D006442:Glycated Hemoglobin; D006680:HLA Antigens; C517652:hemoglobin A1c protein, human