PMID- 7657023
OWN - NLM
STAT- MEDLINE
DCOM- 19951004
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 44
IP  - 9
DP  - 1995 Sep
TI  - Human leukocyte antigen identity and DQ risk alleles in autoantibody-positive 
      siblings of children with IDDM are associated with reduced early insulin 
      response. Childhood Diabetes in Finland (DiMe) Study Group.
PG  - 1021-8
AB  - To investigate the relationship between human leukocyte antigen (HLA)-associated 
      genetic factors and the development of beta-cell dysfunction, we performed 
      sequential intravenous glucose tolerance tests (IVGTTs) on 81 islet cell antibody 
      (ICA)-positive and/or insulin autoantibody-positive healthy siblings of children 
      with newly diagnosed insulin-dependent diabetes mellitus (IDDM). A lower glucose 
      disappearance rate (Kg) (P < 0.5) and decreased first-phase insulin response 
      (FPIR) (P < 0.05) were observed on multiple occasions in HLA-identical siblings 
      compared with the haploidentical or nonidentical ones. Siblings carrying the 
      DQB1*0302/0201, -0302/x, or -0201/x genotype also had lower FPIRs (P < or = 0.05) 
      at several time points than those with no DQB1 risk genotype. When all IVGTTs 
      were taken into account, DQB1*0302/0201 heterozygous siblings had an abnormally 
      low FPIR (< 45 mU/l; 3rd percentile) in at least one test more often than did 
      siblings with no DQB1 risk genotype (50.0% vs. 6.1%; P = 0.001). Siblings 
      carrying either the DQB1*0602 or the DQB1*0603 protective allele had lower serum 
      peak ICA and glutamic acid decarboxylase (GAD)65 antibody levels (P = 0.023 and 
      0.007, respectively) and higher FPIRs on several occasions (P < 0.05) than those 
      with the DQB1 risk genotypes. Progression to IDDM was related to both HLA 
      identity and the presence of the DQB1*0302/0201 genotype. Normal Kg and FPIR 
      levels were observed in siblings who were positive for only insulin autoantibody, 
      and none of them developed IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Veijola, R
AU  - Veijola R
AD  - Department of Pediatrics, University of Oulu, Finland.
FAU - Vahasalo, P
AU  - Vahasalo P
FAU - Tuomilehto-Wolf, E
AU  - Tuomilehto-Wolf E
FAU - Reijonen, H
AU  - Reijonen H
FAU - Kulmala, P
AU  - Kulmala P
FAU - Ilonen, J
AU  - Ilonen J
FAU - Akerblom, H K
AU  - Akerblom HK
FAU - Knip, M
AU  - Knip M
LA  - eng
GR  - R01 HD037957/HD/NICHD NIH HHS/United States
GR  - DK-37957/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Autoantibodies)
RN  - 0 (Blood Glucose)
RN  - 0 (HLA Antigens)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Insulin)
RN  - 0 (islet cell antibody)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Alleles
MH  - Autoantibodies/*blood
MH  - Blood Glucose/metabolism
MH  - Child
MH  - Diabetes Mellitus, Type 1/epidemiology/*genetics/*immunology
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - *Glucose Tolerance Test
MH  - Glutamate Decarboxylase/immunology
MH  - HLA Antigens/blood/genetics
MH  - HLA-DQ Antigens/blood/*genetics
MH  - HLA-DQ beta-Chains
MH  - Haploidy
MH  - *Histocompatibility Testing
MH  - Humans
MH  - Insulin/blood/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/immunology/metabolism
MH  - Male
MH  - Nuclear Family
MH  - Probability
MH  - Risk Factors
MH  - Time Factors
EDAT- 1995/09/01 00:00
MHDA- 1995/09/01 00:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 1995/09/01 00:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - 10.2337/diab.44.9.1021 [doi]
PST - ppublish
SO  - Diabetes. 1995 Sep;44(9):1021-8. doi: 10.2337/diab.44.9.1021.