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
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ISSN:1399-543X, 1399-5448, 1399-5448
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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.
AbstractList 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. 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. 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). 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.
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. 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. 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 ( less than or equal to 30 mu U/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 less than or equal to 30 mu U/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). 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.
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.
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.
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.
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.AIMSChildren 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.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.METHODSIn 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.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).RESULTSAll 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).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.CONCLUSIONSecondary 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 Cilio, Corrado
Jonsdottir, Berglind
Jönsson, Björn
Andersson, Cecilia
Cedervall, Elisabeth
Elding Larsson, Helena
Carlsson, Annelie
Ivarsson, Sten-Anders
Neiderud, Jan
Lernmark, Åke
Larsson, Karin
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Andersson, Cecilia
Larsson, Helena E
Edgren, Joakim
Brundin, Charlotte
Carlsson, Annelie
Neiderud, Jan
Nilsson, Caroline
Ivarsson, Sten
Larsson, Karin
Hemmendal, Jennifer
Cilio, Corrado
Jonsdottir, Berglind
Winqvist, Annika
Arvastsson, Jeanette
Persson, Lars Åke
Gard, Thomas
Mestan, Zeliha
Nilsson, Anita
Lindberg, Bengt
Örtqvist, Eva
Jönsson, Ida
Olsson, Ann
Jönsson, Björn
Cederwall, Elisabeth
Meineche, Susanne Bach
Hansson, Gertie
Wigheden, Ingrid
Lernmark, Åke
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Copyright 2013 John Wiley & Sons A/S
2013 John Wiley & Sons A/S.
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Issue 5
Keywords FPIR
ZnT8
secondary prevention
insulin autoantibodies
T1D
IA-2 autoantibodies
HLA genotype
diabetes mellitus
zinc transporter
glucose tolerance
GAD65 autoantibodies
Language English
License 2013 John Wiley & Sons A/S.
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Notes 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
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Swedish Childhood Diabetes Foundation
Swedish Diabetes Association
the Knut and Alice Wallenberg Foundation
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PublicationTitle Pediatric diabetes
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References Stene LC, Barriga K, Hoffman M et al. Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). Pediatr Diabetes 2006: 7: 247-253.
Karvonen M, Pitkaniemi J, Tuomilehto J. The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group. Diabetes Care 1999: 22: 1066-1070.
Karlberg J, Luo ZC, Albertsson-Wikland K. Body mass index reference values (mean and SD) for Swedish children. Acta Paediatr 2001: 90: 1427-1434.
Ilonen J, Sjoroos M, Knip M et al. Estimation of genetic risk for type 1 diabetes. Am J Med Genet 2002: 115: 30-36.
Bingley PJ, Christie MR, Bonifacio E et al. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 1994: 43: 1304-1310.
Ranke MB. Diagnostics of Endocrine Function in Children and Adolescents3rd revised and extended edition. Basel: Karger, 2003: 321-327.
Mrena S, Savola K, Kulmala P, Akerblom HK, Knip M. Natural course of preclinical type 1 diabetes in siblings of affected children. Acta Paediatr 2003: 92: 1403-1410.
Siljander HT, Veijola R, Reunanen A, Virtanen SM, Akerblom HK, Knip M. Prediction of type 1 diabetes among siblings of affected children and in the general population. Diabetologia 2007: 50: 2272-2275.
Schlosser M, Mueller PW, Torn C, Bonifacio E, Bingley PJ. Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies. Diabetologia 2010: 53: 2611-2620.
Yu L, Boulware DC, Beam CA et al. Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies. Diabetes Care 2012: 35: 1213-1218.
Barker JM, Barriga KJ, Yu L et al. Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab 2004: 89: 3896-3902.
Nejentsev S, Sjoroos M, Soukka T et al. Population-based genetic screening for the estimation of type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci. Diabet Med 1999: 16: 985-992.
Pundziute-Lycka A, Dahlquist G, Urbonaite B, Zalinkevicius R. Time trend of childhood type 1 diabetes incidence in Lithuania and Sweden, 1983-2000. Acta Paediatr 2004: 93: 1519-1524.
Orban T, Sosenko JM, Cuthbertson D et al. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care 2009: 32: 2269-2274.
Lampasona V, Schlosser M, Mueller PW et al. Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin Chem 2011: 57: 1693-1702.
Bingley PJ, Williams AJ, Gale EA. Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials. Diabetes Care 1999: 22: 1796-1801.
Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001: 358: 221-229.
Keskinen P, Korhonen S, Kupila A et al. First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes. Diabetologia 2002: 45: 1639-1648.
Andersson C, Vaziri-Sani F, Delli AJ et al; the BDD Study group. Triple-specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes [Epub 11 September 2012].
Bingley PJ, Mahon JL, Gale EA. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetes Care 2008: 31: 146-150.
Harjutsalo V, Sjoberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008: 371: 1777-1782.
Andersson C, Larsson K, Vaziri-Sani F et al. The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes. Autoimmunity 2011: 44: 394-405.
Xu P, Beam CA, Cuthbertson D, Sosenko JM, Skyler JS, Krischer JP. Prognostic accuracy of immunologic and metabolic markers for type 1 diabetes in a high-risk population: receiver operating characteristic analysis. Diabetes Care 2012: 35: 1975-1980.
Kukko M, Kimpimaki T, Korhonen S et al. Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 2005: 90: 2712-2717.
Lynch KF, Lernmark B, Merlo J, Cilio CM, Ivarsson SA, Lernmark A. Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype. J Perinatol 2008: 28: 211-217.
Redondo MJ, Babu S, Zeidler A et al. Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes. J Clin Endocrinol Metab 2006: 91: 1705-1713.
Ziegler AG, Pflueger M, Winkler C et al. Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children. J Autoimmun 2011: 37: 3-7.
Sosenko JM, Skyler JS, Herold KC, Palmer JP. The metabolic progression to type 1 diabetes as indicated by serial oral glucose tolerance testing in the Diabetes Prevention Trial-type 1. Diabetes 2012: 61: 1331-1337.
Wenzlau JM, Juhl K, Yu L et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007: 104: 17040-17045.
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References_xml – reference: Yu L, Boulware DC, Beam CA et al. Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies. Diabetes Care 2012: 35: 1213-1218.
– reference: Mrena S, Savola K, Kulmala P, Akerblom HK, Knip M. Natural course of preclinical type 1 diabetes in siblings of affected children. Acta Paediatr 2003: 92: 1403-1410.
– reference: Ilonen J, Sjoroos M, Knip M et al. Estimation of genetic risk for type 1 diabetes. Am J Med Genet 2002: 115: 30-36.
– reference: Karlberg J, Luo ZC, Albertsson-Wikland K. Body mass index reference values (mean and SD) for Swedish children. Acta Paediatr 2001: 90: 1427-1434.
– reference: Bingley PJ, Williams AJ, Gale EA. Optimized autoantibody-based risk assessment in family members. Implications for future intervention trials. Diabetes Care 1999: 22: 1796-1801.
– reference: Andersson C, Larsson K, Vaziri-Sani F et al. The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes. Autoimmunity 2011: 44: 394-405.
– reference: Bingley PJ, Christie MR, Bonifacio E et al. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes 1994: 43: 1304-1310.
– reference: Xu P, Beam CA, Cuthbertson D, Sosenko JM, Skyler JS, Krischer JP. Prognostic accuracy of immunologic and metabolic markers for type 1 diabetes in a high-risk population: receiver operating characteristic analysis. Diabetes Care 2012: 35: 1975-1980.
– reference: Wenzlau JM, Juhl K, Yu L et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007: 104: 17040-17045.
– reference: Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001: 358: 221-229.
– reference: Keskinen P, Korhonen S, Kupila A et al. First-phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes. Diabetologia 2002: 45: 1639-1648.
– reference: Harjutsalo V, Sjoberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008: 371: 1777-1782.
– reference: Orban T, Sosenko JM, Cuthbertson D et al. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care 2009: 32: 2269-2274.
– reference: Nejentsev S, Sjoroos M, Soukka T et al. Population-based genetic screening for the estimation of type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci. Diabet Med 1999: 16: 985-992.
– reference: Kukko M, Kimpimaki T, Korhonen S et al. Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 2005: 90: 2712-2717.
– reference: Sosenko JM, Skyler JS, Herold KC, Palmer JP. The metabolic progression to type 1 diabetes as indicated by serial oral glucose tolerance testing in the Diabetes Prevention Trial-type 1. Diabetes 2012: 61: 1331-1337.
– reference: Siljander HT, Veijola R, Reunanen A, Virtanen SM, Akerblom HK, Knip M. Prediction of type 1 diabetes among siblings of affected children and in the general population. Diabetologia 2007: 50: 2272-2275.
– reference: Lynch KF, Lernmark B, Merlo J, Cilio CM, Ivarsson SA, Lernmark A. Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype. J Perinatol 2008: 28: 211-217.
– reference: Redondo MJ, Babu S, Zeidler A et al. Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes. J Clin Endocrinol Metab 2006: 91: 1705-1713.
– reference: Pundziute-Lycka A, Dahlquist G, Urbonaite B, Zalinkevicius R. Time trend of childhood type 1 diabetes incidence in Lithuania and Sweden, 1983-2000. Acta Paediatr 2004: 93: 1519-1524.
– reference: Andersson C, Vaziri-Sani F, Delli AJ et al; the BDD Study group. Triple-specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes [Epub 11 September 2012].
– reference: Barker JM, Barriga KJ, Yu L et al. Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab 2004: 89: 3896-3902.
– reference: Lampasona V, Schlosser M, Mueller PW et al. Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin Chem 2011: 57: 1693-1702.
– reference: Ziegler AG, Pflueger M, Winkler C et al. Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children. J Autoimmun 2011: 37: 3-7.
– reference: Bingley PJ, Mahon JL, Gale EA. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetes Care 2008: 31: 146-150.
– reference: Ranke MB. Diagnostics of Endocrine Function in Children and Adolescents3rd revised and extended edition. Basel: Karger, 2003: 321-327.
– reference: Karvonen M, Pitkaniemi J, Tuomilehto J. The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group. Diabetes Care 1999: 22: 1066-1070.
– reference: Stene LC, Barriga K, Hoffman M et al. Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). Pediatr Diabetes 2006: 7: 247-253.
– reference: Schlosser M, Mueller PW, Torn C, Bonifacio E, Bingley PJ. Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies. Diabetologia 2010: 53: 2611-2620.
– article-title: Triple‐specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes
  publication-title: Pediatr Diabetes
– volume: 35
  start-page: 1213
  year: 2012
  end-page: 1218
  article-title: Zinc transporter‐8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies
  publication-title: Diabetes Care
– volume: 358
  start-page: 221
  year: 2001
  end-page: 229
  article-title: Type 1 diabetes: new perspectives on disease pathogenesis and treatment
  publication-title: Lancet
– volume: 93
  start-page: 1519
  year: 2004
  end-page: 1524
  article-title: Time trend of childhood type 1 diabetes incidence in Lithuania and Sweden, 1983–2000
  publication-title: Acta Paediatr
– volume: 44
  start-page: 394
  year: 2011
  end-page: 405
  article-title: The three ZNT8 autoantibody variants together improve the diagnostic sensitivity of childhood and adolescent type 1 diabetes
  publication-title: Autoimmunity
– volume: 35
  start-page: 1975
  year: 2012
  end-page: 1980
  article-title: Prognostic accuracy of immunologic and metabolic markers for type 1 diabetes in a high‐risk population: receiver operating characteristic analysis
  publication-title: Diabetes Care
– volume: 7
  start-page: 247
  year: 2006
  end-page: 253
  article-title: Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY)
  publication-title: Pediatr Diabetes
– start-page: 321
  year: 2003
  end-page: 327
– volume: 89
  start-page: 3896
  year: 2004
  end-page: 3902
  article-title: Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY)
  publication-title: J Clin Endocrinol Metab
– volume: 57
  start-page: 1693
  year: 2011
  end-page: 1702
  article-title: Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8
  publication-title: Clin Chem
– volume: 22
  start-page: 1796
  year: 1999
  end-page: 1801
  article-title: Optimized autoantibody‐based risk assessment in family members. Implications for future intervention trials
  publication-title: Diabetes Care
– volume: 16
  start-page: 985
  year: 1999
  end-page: 992
  article-title: Population‐based genetic screening for the estimation of type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA‐DQB1, HLA‐DQA1 and HLA‐DRB1 loci
  publication-title: Diabet Med
– volume: 22
  start-page: 1066
  year: 1999
  end-page: 1070
  article-title: The onset age of type 1 diabetes in Finnish children has become younger. The Finnish Childhood Diabetes Registry Group
  publication-title: Diabetes Care
– volume: 32
  start-page: 2269
  year: 2009
  end-page: 2274
  article-title: Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial‐Type 1
  publication-title: Diabetes Care
– volume: 31
  start-page: 146
  year: 2008
  end-page: 150
  article-title: Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)
  publication-title: Diabetes Care
– volume: 92
  start-page: 1403
  year: 2003
  end-page: 1410
  article-title: Natural course of preclinical type 1 diabetes in siblings of affected children
  publication-title: Acta Paediatr
– volume: 90
  start-page: 2712
  year: 2005
  end-page: 2717
  article-title: Dynamics of diabetes‐associated autoantibodies in young children with human leukocyte antigen‐conferred risk of type 1 diabetes recruited from the general population
  publication-title: J Clin Endocrinol Metab
– volume: 37
  start-page: 3
  year: 2011
  end-page: 7
  article-title: Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children
  publication-title: J Autoimmun
– volume: 90
  start-page: 1427
  year: 2001
  end-page: 1434
  article-title: Body mass index reference values (mean and SD) for Swedish children
  publication-title: Acta Paediatr
– volume: 61
  start-page: 1331
  year: 2012
  end-page: 1337
  article-title: The metabolic progression to type 1 diabetes as indicated by serial oral glucose tolerance testing in the Diabetes Prevention Trial‐type 1
  publication-title: Diabetes
– volume: 45
  start-page: 1639
  year: 2002
  end-page: 1648
  article-title: First‐phase insulin response in young healthy children at genetic and immunological risk for Type I diabetes
  publication-title: Diabetologia
– volume: 50
  start-page: 2272
  year: 2007
  end-page: 2275
  article-title: Prediction of type 1 diabetes among siblings of affected children and in the general population
  publication-title: Diabetologia
– volume: 115
  start-page: 30
  year: 2002
  end-page: 36
  article-title: Estimation of genetic risk for type 1 diabetes
  publication-title: Am J Med Genet
– volume: 28
  start-page: 211
  year: 2008
  end-page: 217
  article-title: Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high‐risk genotype
  publication-title: J Perinatol
– volume: 53
  start-page: 2611
  year: 2010
  end-page: 2620
  article-title: Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies
  publication-title: Diabetologia
– volume: 104
  start-page: 17040
  year: 2007
  end-page: 17045
  article-title: The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes
  publication-title: Proc Natl Acad Sci U S A
– volume: 371
  start-page: 1777
  year: 2008
  end-page: 1782
  article-title: Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study
  publication-title: Lancet
– volume: 43
  start-page: 1304
  year: 1994
  end-page: 1310
  article-title: Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody‐positive relatives
  publication-title: Diabetes
– volume: 91
  start-page: 1705
  year: 2006
  end-page: 1713
  article-title: Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes
  publication-title: J Clin Endocrinol Metab
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Snippet Aims Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic...
Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control...
AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic...
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StartPage 341
SubjectTerms 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
Title Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study
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