ArticleThe Journal of clinical investigation2004
Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 217 citations in OpenAlex.
- Effect of High-Dose Oral Insulin in Children With Stage 1 Type 1 Diabetes: The Fr1da Insulin Intervention Randomized Controlled Trial.Diabetes care · 2026Trial
- Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial.Diabetologia · 2021Trial
- Zinc transporter 8 (ZnT8) autoantibody epitope specificity and affinity examined with recombinant ZnT8 variant proteins in specific ZnT8R and ZnT8W autoantibody-positive type 1 diabetes patients.Clinical and experimental immunology · 2015Trial
- Trial
- Surface plasmon resonance reveals a different pattern of proinsulin autoantibodies concentration and affinity in diabetic patients.PloS one · 2012Trial
- Rituximab selectively suppresses specific islet antibodies.Diabetes · 2011Trial
- Impact of intranasal insulin on insulin antibody affinity and isotypes in young children with HLA-conferred susceptibility to type 1 diabetes.Diabetes care · 2011Trial
- Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes.Diabetes · 2011Trial
- Effect of oral insulin on insulin autoantibody levels in the Diabetes Prevention Trial Type 1 oral insulin study.Diabetologia · 2007Trial
- Improved prediction of symptomatic type 1 diabetes using a luciferase-based assay to measure (pro)insulin autoantibodies.Diabetic medicine : a journal of the British Diabetic Association · 2026Observational
- Identifying Insulin Autoantibodies With Differential Risk in Type 1 Diabetes With a Novel Bridging ELISA.Diabetes · 2026Article
- Heterogeneity between insulin and proinsulin in the potency for insulin autoantibodies in newly diagnosed type 1 diabetes children.Clinical and experimental immunology · 2026Article
- Inverted insulin to C-Peptide ratios in neonatal intensive care: is there something we don't know?Frontiers in pediatrics · 2026Article
- Evaluation of proinsulin(F25D) as a targeting ligand for insulin-binding B cells in autoimmune diabetes.Drug delivery and translational research · 2026Article
- Molecular Portrait of Autoantigens in Type 1 Diabetes.Biomolecules · 2025Review
- Comparative Analysis of the Sensitivity, Specificity, Concordance, and 5-Year Predictive Power of Diabetes-Related Autoantibody Assays.Diabetes · 2025Article
- Type 1 diabetes risk factors, risk prediction and presymptomatic detection: Evidence and guidance for screening.Diabetes, obesity & metabolism · 2025Review
- From Prediction to Prevention: The Intricacies of Islet Autoantibodies in Type 1 Diabetes.Current diabetes reports · 2025Review
- Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset.Nature communications · 2025Article
- Oral tolerogenic vaccine combined with gastrin restores immune tolerance and beta-cell function in NOD mice with Type 1 diabetes.Frontiers in immunology · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Children at risk for type 1 diabetes can develop early insulin autoantibodies (IAAs). Many, but not all, of these children subsequently develop multiple islet autoantibodies and diabetes. To determine whether disease progression is reflected by autoantibody maturity, IAA affinity was measured by competitive radiobinding assay in first and subsequent IAA-positive samples from children followed from birth in the BABYDIAB cohort. IAA affinity in first positive samples ranged from less than 10(6) l/mol to more than 10(11) l/mol. High affinity was associated with HLA DRB1*04, young age of IAA appearance, and subsequent progression to multiple islet autoantibodies or type 1 diabetes. IAA affinity in multiple antibody-positive children was on average 100-fold higher than in children who remained single IAA positive or became autoantibody negative. All high-affinity IAAs required conservation of human insulin A chain residues 8-13 and were reactive with proinsulin. In contrast, most lower-affinity IAAs were dependent on COOH-terminal B chain residues and did not bind proinsulin. These data are consistent with the concept that type 1 diabetes is associated with sustained early exposure to (pro)insulin in the context of HLA DR4 and show that high-affinity proinsulin-reactive IAAs identify children with the highest diabetes risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.