PMID- 28597957
OWN - NLM
STAT- MEDLINE
DCOM- 20181102
LR  - 20181102
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 19
IP  - 2
DP  - 2018 Mar
TI  - Early childhood infections precede development of beta-cell autoimmunity and type 
      1 diabetes in children with HLA-conferred disease risk.
PG  - 293-299
LID - 10.1111/pedi.12547 [doi]
AB  - BACKGROUND: The etiology of type 1 diabetes (T1D) is largely unknown. Infections 
      and microbial exposures are believed to play a role in the pathogenesis and in 
      the development of islet autoimmunity in genetically susceptible individuals. 
      OBJECTIVE: To assess the relationships between early childhood infections, islet 
      autoimmunity, and progression to T1D in genetically predisposed children. 
      METHODS: Children with human leukocyte antigen (HLA)-conferred disease 
      susceptibility (N=790; 51.5% males) from Finland (n = 386), Estonia (n = 322), 
      and Russian Karelia (n = 82) were observed from birth up to the age of 3 years. 
      Children attended clinical visits at the age of 3, 6, 12, 18, 24, and 36 months. 
      Serum samples for analyzing T1D-associated autoimmune markers were collected and 
      health data recorded during the visits. RESULTS: Children developing islet 
      autoimmunity (n = 46, 5.8%) had more infections during the first year of life 
      (3.0 vs 3.0, mean rank 439.1 vs 336.2; P = .001) and their first infection 
      occurred earlier (3.6 vs 5.0 months; P = .005) than children with no islet 
      autoimmunity. By May 2016, 7 children (0.9%) had developed T1D (progressors). 
      Compared with non-diabetic children, T1D progressors were younger at first 
      infection (2.2 vs 4.9 months; P = .004) and had more infections during the first 
      2 years of life (during each year 6.0 vs 3.0; P = .001 and P = .027, 
      respectively). By 3 years of age, the T1D progressors had twice as many 
      infections as the other children (17.5 vs 9.0; P = .006). CONCLUSIONS: Early 
      childhood infections may play an important role in the pathogenesis of T1D. 
      Current findings may reflect either differences in microbial exposures or early 
      immunological aberrations making diabetes-prone children more susceptible to 
      infections.
CI  - (c) 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Mustonen, N
AU  - Mustonen N
AUID- ORCID: 0000-0003-1208-8954
AD  - Children's Hospital, University of Helsinki and Helsinki University Hospital, 
      Helsinki, Finland.
AD  - Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, 
      Finland.
FAU - Siljander, H
AU  - Siljander H
AUID- ORCID: 0000-0002-6899-2822
AD  - Children's Hospital, University of Helsinki and Helsinki University Hospital, 
      Helsinki, Finland.
AD  - Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, 
      Finland.
FAU - Peet, A
AU  - Peet A
AD  - Department of Pediatrics, University of Tartu and Tartu University Hospital, 
      Tartu, Estonia.
FAU - Tillmann, V
AU  - Tillmann V
AD  - Department of Pediatrics, University of Tartu and Tartu University Hospital, 
      Tartu, Estonia.
FAU - Harkonen, T
AU  - Harkonen T
AD  - Children's Hospital, University of Helsinki and Helsinki University Hospital, 
      Helsinki, Finland.
AD  - Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, 
      Finland.
FAU - Ilonen, J
AU  - Ilonen J
AD  - Immunogenetics Laboratory, University of Turku and Turku University Hospital, 
      Turku, Finland.
FAU - Hyoty, H
AU  - Hyoty H
AD  - Department of Virology, School of Medicine, University of Tampere, Tampere, 
      Finland.
AD  - Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.
FAU - Knip, M
AU  - Knip M
AUID- ORCID: 0000-0003-0474-0033
AD  - Children's Hospital, University of Helsinki and Helsinki University Hospital, 
      Helsinki, Finland.
AD  - Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, 
      Finland.
AD  - Folkhalsan Institute of Genetics, Folkhalsan Research Center, Helsinki, Finland.
AD  - Tampere Center for Child Health Research, Tampere University Hospital, Tampere, 
      Finland.
CN  - DIABIMMUNE Study Group
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20170609
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (HLA-DR Antigens)
SB  - IM
MH  - *Autoimmunity
MH  - *Child Development
MH  - Cohort Studies
MH  - Community-Acquired Infections/blood/epidemiology/genetics/*immunology
MH  - Diabetes Mellitus, Type 1/blood/epidemiology/genetics/*immunology
MH  - Disease Progression
MH  - Disease Susceptibility
MH  - Estonia/epidemiology
MH  - Female
MH  - Finland/epidemiology
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - HLA-DR Antigens/chemistry/genetics
MH  - Humans
MH  - Infant, Newborn
MH  - Insulin-Secreting Cells/*immunology
MH  - Male
MH  - Prediabetic State/blood/genetics/*immunology/physiopathology
MH  - Prospective Studies
MH  - Respiratory Tract Infections/blood/epidemiology/genetics/*immunology
MH  - Risk
MH  - Russia/epidemiology
OTO - NOTNLM
OT  - childhood infections
OT  - islet autoimmunity
OT  - respiratory tract infections
OT  - the hygiene hypothesis
OT  - type 1 diabetes
EDAT- 2017/06/10 06:00
MHDA- 2018/11/06 06:00
CRDT- 2017/06/10 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/04/13 00:00 [revised]
PHST- 2017/05/09 00:00 [accepted]
PHST- 2017/06/10 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2017/06/10 06:00 [entrez]
AID - 10.1111/pedi.12547 [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2018 Mar;19(2):293-299. doi: 10.1111/pedi.12547. Epub 2017 Jun 
      9.