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Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.

Andersson, Cecilia K LU ; Carlsson, Annelie LU ; Cilio, Corrado LU ; Cedervall, Elisabeth; Ivarsson, Sten LU ; Jonsdottir, Berglind LU ; Jönsson, Björn; Larsson, Karin LU ; Neiderud, Jan LU and Lernmark, Åke LU , et al. (2013) In Pediatric Diabetes 14(5). p.341-349
Abstract
AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino... (More)
AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ≤30 μU/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03). CONCLUSION: Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA. (Less)
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type
Contribution to journal
publication status
published
subject
in
Pediatric Diabetes
volume
14
issue
5
pages
341 - 349
publisher
Wiley-Blackwell
external identifiers
  • wos:000322989100004
  • pmid:23469940
  • scopus:84881021878
ISSN
1399-543X
DOI
10.1111/pedi.12023
language
English
LU publication?
yes
id
505f2246-cdac-4257-b7cd-53de77a30016 (old id 3628454)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23469940?dopt=Abstract
date added to LUP
2013-04-04 14:11:57
date last changed
2019-05-14 01:26:12
@article{505f2246-cdac-4257-b7cd-53de77a30016,
  abstract     = {AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ≤30 μU/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03). CONCLUSION: Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA.},
  author       = {Andersson, Cecilia K and Carlsson, Annelie and Cilio, Corrado and Cedervall, Elisabeth and Ivarsson, Sten and Jonsdottir, Berglind and Jönsson, Björn and Larsson, Karin and Neiderud, Jan and Lernmark, Åke and Larsson, Helena},
  issn         = {1399-543X},
  language     = {eng},
  number       = {5},
  pages        = {341--349},
  publisher    = {Wiley-Blackwell},
  series       = {Pediatric Diabetes},
  title        = {Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.},
  url          = {http://dx.doi.org/10.1111/pedi.12023},
  volume       = {14},
  year         = {2013},
}