PMID- 29300921
OWN - NLM
STAT- MEDLINE
DCOM- 20190326
LR  - 20190326
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 103
IP  - 8
DP  - 2018 Aug 1
TI  - Class II HLA Genotype Association With First-Phase Insulin Response Is Explained 
      by Islet Autoantibodies.
PG  - 2870-2878
LID - 10.1210/jc.2017-02040 [doi]
AB  - CONTEXT: A declining first-phase insulin response (FPIR) is characteristic of the 
      disease process leading to clinical type 1 diabetes. It is not known whether 
      reduced FPIR depends on class II human leukocyte antigen (HLA) genotype, islet 
      autoimmunity, or both. OBJECTIVE: To dissect the role of class II HLA DR-DQ 
      genotypes and biochemical islet autoantibodies in the compromised FPIR. DESIGN, 
      SETTING, PARTICIPANTS: A total of 438 children with defined HLA DR-DQ genotype in 
      the prospective Finnish Type 1 Diabetes Prediction and Prevention Study were 
      analyzed for FPIR in a total of 1149 intravenous glucose tolerance tests and were 
      categorized by their HLA DR-DQ genotype and the number of biochemical islet 
      autoantibodies at the time of the first FPIR. Age-adjusted hierarchical linear 
      mixed models were used to analyze repeated measurements of FPIR. MAIN OUTCOME 
      MEASURE: The associations between class II HLA DR-DQ genotype, islet autoantibody 
      status, and FPIR. RESULTS: A strong association between the degree of risk 
      conferred by HLA DR-DQ genotype and positivity for islet autoantibodies existed 
      (P < 0.0001). FPIR was inversely associated with the number of biochemical 
      autoantibodies (P < 0.0001) irrespective of HLA DR-DQ risk group. FPIR decreased 
      over time in children with multiple autoantibodies and increased in children with 
      no biochemical autoantibodies (P < 0.0001 and P = 0.0013, respectively). 
      CONCLUSIONS: The class II HLA DR-DQ genotype association with FPIR was secondary 
      to the association between HLA and islet autoimmunity. Declining FPIR was 
      associated with positivity for multiple islet autoantibodies irrespective of 
      class II HLA DR-DQ genotype.
FAU - Koskinen, Maarit K
AU  - Koskinen MK
AD  - Department of Pediatrics, University of Turku and Turku University Hospital, 
      Turku, Finland.
FAU - Lempainen, Johanna
AU  - Lempainen J
AD  - Department of Pediatrics, University of Turku and Turku University Hospital, 
      Turku, Finland.
AD  - Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and 
      Turku University Hospital, Turku, Finland.
FAU - Loyttyniemi, Eliisa
AU  - Loyttyniemi E
AD  - Department of Biostatistics, University of Turku, Turku, Finland.
FAU - Helminen, Olli
AU  - Helminen O
AD  - Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu 
      University Hospital and University of Oulu, Oulu, Finland.
FAU - Hekkala, Anne
AU  - Hekkala A
AD  - Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu 
      University Hospital and University of Oulu, Oulu, Finland.
FAU - Harkonen, Taina
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 - Kiviniemi, Minna
AU  - Kiviniemi M
AD  - Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and 
      Turku University Hospital, Turku, Finland.
FAU - Simell, Olli
AU  - Simell O
AD  - Department of Pediatrics, University of Turku and Turku University Hospital, 
      Turku, Finland.
FAU - Knip, Mikael
AU  - Knip M
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 Research Center, Helsinki, Finland.
AD  - Tampere Center for Child Health Research, Tampere University Hospital, Tampere, 
      Finland.
FAU - Ilonen, Jorma
AU  - Ilonen J
AD  - Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and 
      Turku University Hospital, Turku, Finland.
FAU - Toppari, Jorma
AU  - Toppari J
AD  - Department of Pediatrics, University of Turku and Turku University Hospital, 
      Turku, Finland.
AD  - Institute of Biomedicine, Research Centre for Integrative Physiology and 
      Pharmacology, University of Turku, Turku, Finland.
FAU - Veijola, Riitta
AU  - Veijola R
AD  - Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu 
      University Hospital and University of Oulu, Oulu, Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Insulin)
SB  - IM
MH  - Adolescent
MH  - Autoantibodies/blood
MH  - Autoimmunity/genetics
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/blood/genetics/*immunology
MH  - Female
MH  - Finland
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glucose Tolerance Test
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DR Antigens/*genetics
MH  - Humans
MH  - Infant
MH  - Insulin/blood/*immunology
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Treatment Outcome
PMC - PMC6097602
EDAT- 2018/01/05 06:00
MHDA- 2019/03/27 06:00
PMCR- 2017/12/28
CRDT- 2018/01/05 06:00
PHST- 2017/09/14 00:00 [received]
PHST- 2017/12/21 00:00 [accepted]
PHST- 2018/01/05 06:00 [pubmed]
PHST- 2019/03/27 06:00 [medline]
PHST- 2018/01/05 06:00 [entrez]
PHST- 2017/12/28 00:00 [pmc-release]
AID - 4780809 [pii]
AID - jcem_201702040 [pii]
AID - 10.1210/jc.2017-02040 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2018 Aug 1;103(8):2870-2878. doi: 10.1210/jc.2017-02040.