title: Clinical, Genetic, and Biochemical Characteristics of Early-Onset Diabetes in the Finnish Population.
abstract: Major advances have been made in the classification and genetics of monogenic diabetes in infancy.
  
  
  
  The objective of the study was to characterize different forms of diabetes diagnosed during the first year of life.
  
  
  
  Patients diagnosed with diabetes before the age of 1 year in 10 Finnish hospitals from 1980 to 2014 were included.
  
  
  
  The study was conducted at Kuopio University Hospital and University of Eastern Finland.
  
  
  
  Patients were identified through diagnosis-based searches from hospital registries including 93 children, of whom 64 participated.
  
  
  
  DNA sample for sequencing, serum sample, and medical records interventions were included.
  
  
  
  Incidence of diabetes during the first year of life, sequencing results, human leukocyte antigen (HLA) genotypes, and islet autoantibodies were measured.
  
  
  
  The incidence of diabetes diagnosed during the first 12 months was 4.4/100 000/year. Three novel and 11 previously described mutations were found in 22 patients from 15 families in the KCNJ11, ABCC8, INS, GCK, FOXP, STAT3, and RFX6 genes. Positive islet autoantibodies were observed in 40.0% of the patients diagnosed during the first 0-6 months of life vs 70.8% of the patients diagnosed between ages of 7 to 12 months. A total of 85.7% of the patients carrying protective HLA genotypes were mutation-positive compared to 7.7% of the patients having high-risk genotypes (P = .001).
  
  
  
  Mutations in the K-ATP channel and INS genes were the most common cause of early diagnosed monogenic diabetes. After 6 months of age, patients with diabetes had high HLA risk genotypes and islet autoantibodies, reflecting the autoimmune character of diabetes in that age group.
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Huopio
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi J
authors.initials: PJ
authors.lastname: Miettinen
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Nykänen
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Keskinen
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kirsti
authors.initials: K
authors.lastname: Näntö-Salonen
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Vangipurapu
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Joose
authors.initials: J
authors.lastname: Raivo
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Alena
authors.initials: A
authors.lastname: Stančáková
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Männistö
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Kuulasmaa
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Otonkoski
authors.affiliation: Department of Pediatrics (H.H., J.M.), University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland; Children's Hospital (P.J.M., M.K., T.O.), University of Helsinki, and Helsinki University Hospital, Helsinki, Finland; Immunogenetics Laboratory (J.I.), University of Turku, and Turku University Hospital, Turku, Finland; Department of Pediatrics (P.N.), Mikkeli Central Hospital, Mikkeli, Finland; Department of Pediatrics (R.V.), Medical Research Center, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Pediatrics (P.K.), Tampere University Hospital, Tampere, Finland; Department of Pediatrics (K.N.-S.), Turku University Hospital, Turku, Finland; Institute of Clinical Medicine (J.V., J.R., A.S., T.K., M.L.), Internal Medicine, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine (M.L.), Internal Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D012042:Registries
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying