PMID- 27167055
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20180501
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 101
IP  - 8
DP  - 2016 Aug
TI  - Clinical, Genetic, and Biochemical Characteristics of Early-Onset Diabetes in the 
      Finnish Population.
PG  - 3018-26
LID - 10.1210/jc.2015-4296 [doi]
AB  - CONTEXT: Major advances have been made in the classification and genetics of 
      monogenic diabetes in infancy. OBJECTIVE: The objective of the study was to 
      characterize different forms of diabetes diagnosed during the first year of life. 
      DESIGN: Patients diagnosed with diabetes before the age of 1 year in 10 Finnish 
      hospitals from 1980 to 2014 were included. SETTING: The study was conducted at 
      Kuopio University Hospital and University of Eastern Finland. PATIENTS: Patients 
      were identified through diagnosis-based searches from hospital registries 
      including 93 children, of whom 64 participated. INTERVENTIONS: DNA sample for 
      sequencing, serum sample, and medical records interventions were included. MAIN 
      OUTCOME MEASURES: Incidence of diabetes during the first year of life, sequencing 
      results, human leukocyte antigen (HLA) genotypes, and islet autoantibodies were 
      measured. RESULTS: 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). CONCLUSIONS: 
      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.
FAU - Huopio, Hanna
AU  - Huopio H
AD  - 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.
FAU - Miettinen, Paivi J
AU  - Miettinen PJ
AD  - 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.
FAU - Ilonen, Jorma
AU  - Ilonen J
AD  - 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.
FAU - Nykanen, Paivi
AU  - Nykanen P
AD  - 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.
FAU - Veijola, Riitta
AU  - Veijola R
AD  - 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.
FAU - Keskinen, Paivi
AU  - Keskinen P
AD  - 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.
FAU - Nanto-Salonen, Kirsti
AU  - Nanto-Salonen K
AD  - 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.
FAU - Vangipurapu, Jagadish
AU  - Vangipurapu J
AD  - 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.
FAU - Raivo, Joose
AU  - Raivo J
AD  - 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.
FAU - Stancakova, Alena
AU  - Stancakova A
AD  - 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.
FAU - Mannisto, Jonna
AU  - Mannisto J
AD  - 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.
FAU - Kuulasmaa, Teemu
AU  - Kuulasmaa T
AD  - 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.
FAU - Knip, Mikael
AU  - Knip M
AD  - 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.
FAU - Otonkoski, Timo
AU  - Otonkoski T
AD  - 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.
FAU - Laakso, Markku
AU  - Laakso M
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160511
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA Antigens)
RN  - 0 (Insulin)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
SB  - IM
MH  - Age of Onset
MH  - Autoantibodies/blood
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Diabetes Mellitus, Type 1/*blood/*epidemiology/*genetics
MH  - Female
MH  - Finland/epidemiology
MH  - Genotype
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Incidence
MH  - Infant
MH  - Infant, Newborn
MH  - Insulin/genetics
MH  - Islets of Langerhans/immunology
MH  - Male
MH  - Potassium Channels, Inwardly Rectifying/genetics
MH  - Registries
EDAT- 2016/05/12 06:00
MHDA- 2017/06/27 06:00
CRDT- 2016/05/12 06:00
PHST- 2016/05/12 06:00 [entrez]
PHST- 2016/05/12 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
AID - 10.1210/jc.2015-4296 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2016 Aug;101(8):3018-26. doi: 10.1210/jc.2015-4296. Epub 
      2016 May 11.