PMID- 15292324 OWN - NLM STAT- MEDLINE DCOM- 20040903 LR - 20111117 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 89 IP - 8 DP - 2004 Aug TI - Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). PG - 3896-902 AB - Diabetes Autoimmunity Study in the Young (DAISY) has followed 1972 children for islet autoimmunity and diabetes: 837 first-degree relatives of persons with type 1 diabetes and 1135 general population newborns identified through human leukocyte antigen (HLA) screening. During follow-up of 4.06 yr (range, 0.17-9 yr), serial determination of autoantibodies to glutamic acid decarboxylase, protein tyrosine phosphatase IA2, and insulin has generated approximately 20,000 results. Among 162 children with at least one positive autoantibody, in 31% the test was false positive (autoantibodies were negative twice on blinded duplicate aliquots), in 31% it was transiently positive (confirmed on blinded duplicate aliquots but negative on follow-up), and in 36% it was persistently positive. Using proportional hazards modeling, the HLA-DR3/4 DQ8 genotype, another positive autoantibody at the first positive visit, and level of autoantibody were predictive of persistent positivity. Only HLA-DR3/4 DQ8 genotype was predictive of progression to diabetes in proportional hazards modeling. This prospective study reveals that cross-sectional determination of islet autoantibodies in a population with relatively low previous probability of autoimmunity identifies as "positive" a large number of individuals who are either false or transiently positive. Predictive value of autoantibodies increases with blinded duplicate and independent sample retesting and incorporation of the level of autoantibody in the predictive algorithm. FAU - Barker, Jennifer M AU - Barker JM AD - Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. jennifer.barker@uchsc.edu FAU - Barriga, Katherine J AU - Barriga KJ FAU - Yu, Liping AU - Yu L FAU - Miao, Dongmei AU - Miao D FAU - Erlich, Henry A AU - Erlich HA FAU - Norris, Jill M AU - Norris JM FAU - Eisenbarth, George S AU - Eisenbarth GS FAU - Rewers, Marian AU - Rewers M CN - Diabetes Autoimmunity Study in the Young LA - eng GR - AI 39213/AI/NIAID NIH HHS/United States GR - AI 50864/AI/NIAID NIH HHS/United States GR - DK 32083/DK/NIDDK NIH HHS/United States GR - DK 32493/DK/NIDDK NIH HHS/United States GR - DK 57516/DK/NIDDK NIH HHS/United States GR - S-M01-RR00051/RR/NCRR NIH HHS/United States 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 - 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-DQ8 antigen) RN - 0 (HLA-DR3 Antigen) RN - 0 (HLA-DR4 Antigen) RN - 0 (Insulin) RN - EC 3.1.3.48 (PTPRN protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (Receptor-Like Protein Tyrosine Phosphatases, Class 8) RN - EC 4.1.1.15 (Glutamate Decarboxylase) SB - IM MH - Autoantibodies/*analysis MH - Child MH - Child, Preschool MH - Cohort Studies MH - Diabetes Mellitus, Type 1/genetics/*immunology MH - Disease Progression MH - False Positive Reactions MH - Follow-Up Studies MH - Genotype MH - Glutamate Decarboxylase/immunology MH - HLA-DQ Antigens/immunology MH - HLA-DR3 Antigen/immunology MH - HLA-DR4 Antigen/immunology MH - Humans MH - Infant MH - Infant, Newborn MH - Insulin/immunology MH - Predictive Value of Tests MH - Prognosis MH - Proportional Hazards Models MH - Prospective Studies MH - Protein Tyrosine Phosphatase, Non-Receptor Type 1 MH - Protein Tyrosine Phosphatases/immunology MH - Receptor-Like Protein Tyrosine Phosphatases, Class 8 MH - Single-Blind Method EDAT- 2004/08/05 05:00 MHDA- 2004/09/04 05:00 CRDT- 2004/08/05 05:00 PHST- 2004/08/05 05:00 [pubmed] PHST- 2004/09/04 05:00 [medline] PHST- 2004/08/05 05:00 [entrez] AID - 89/8/3896 [pii] AID - 10.1210/jc.2003-031887 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2004 Aug;89(8):3896-902. doi: 10.1210/jc.2003-031887.