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

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 childre...

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Vydáno v:	Pediatric diabetes Ročník 14; číslo 5; s. 341 - 349
Hlavní autoři:	Andersson, Cecilia, Carlsson, Annelie, Cilio, Corrado, Cedervall, Elisabeth, Ivarsson, Sten-Anders, Jonsdottir, Berglind, Jönsson, Björn, Larsson, Karin, Neiderud, Jan, Lernmark, Åke, Elding Larsson, Helena
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Former Munksgaard John Wiley & Sons A/S 01.08.2013
Témata:	Autoantibodies - blood Cation Transport Proteins - genetics Cation Transport Proteins - immunology Child Child, Preschool Clinical Medicine diabetes mellitus Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - prevention & control Endocrinology and Diabetes Endokrinologi och diabetes Female FPIR GAD65 autoantibodies Glucose - metabolism Glucose Intolerance - immunology glucose tolerance Glucose Tolerance Test Glutamate Decarboxylase - immunology HLA Antigens - immunology HLA genotype HLA-DQ Antigens - immunology Humans IA-2 autoantibodies Insulin - immunology insulin autoantibodies Insulin-Secreting Cells - immunology Klinisk medicin Male Medical and Health Sciences Medicin och hälsovetenskap Pediatrics Pediatrik Receptor-Like Protein Tyrosine Phosphatases, Class 8 - immunology secondary prevention T1D zinc transporter Zinc Transporter 8 ZnT8 FPIR ZnT8 secondary prevention insulin autoantibodies T1D IA-2 autoantibodies HLA genotype diabetes mellitus zinc transporter glucose tolerance GAD65 autoantibodies
ISSN:	1399-543X, 1399-5448, 1399-5448
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Shrnutí:	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.
Bibliografie:	Swedish Research Council - No. 14064 National Institutes of Health - No. DK26190 UMAS Fund ark:/67375/WNG-JTDH4VRB-R the Juvenile Diabetes Research Foundation - No. 17-2011-576 ArticleID:PEDI12023 the Skåne County Council for Research and Development istex:E5D81344B08CF0B3EDDEEE1A762B72DE03934E6B Swedish Childhood Diabetes Foundation Swedish Diabetes Association the Knut and Alice Wallenberg Foundation See Appendix. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	1399-543X 1399-5448 1399-5448
DOI:	10.1111/pedi.12023