ArticleDiabetes care2024
Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in HLA DR4-DQ8 Participants in the TrialNet Oral Insulin Prevention Trial (TN07).
Article in Diabetes care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
15 citing papers in PubMed.
- Effect of High-Dose Oral Insulin in Children With Stage 1 Type 1 Diabetes: The Fr1da Insulin Intervention Randomized Controlled Trial.Diabetes care · 2026Trial
- Baseline Insulin Secretion Determines Response to Abatacept in Stage 1 Type 1 Diabetes.Diabetes · 2026Trial
- From genes to environment: A life-course approach to prevent pediatric autoimmune diseases.World journal of clinical pediatrics · 2026Review
- Reducing Diabetic Ketoacidosis in Pediatric Type 1 Diabetes: The Impact of Screening Programs and Early Disease-Modifying Treatment.Journal of clinical medicine · 2026Review
- Unbiased discovery of autoreactive type 1 diabetes T-cell receptors that bind specific hybrid insulin peptides.Research square · 2026Article
- Genetic Predictors of Response to Oral Insulin for Type 1 Diabetes Prevention.Diabetes care · 2026Article
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Profiling associations of interactive ligand-receptors (HLA class I and KIR gene products) with the progression to type 1 diabetes among seroconverted participants.Diabetologia · 2025Article
- Review
- The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetes care · 2025Review
- Are We Ready With Prevention for Type 1 Diabetes?Diabetes/metabolism research and reviews · 2025Review
- The heterogeneity of type 1 diabetes: implications for pathogenesis, prevention, and treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2025Review
- Type 1 Diabetes TrialNet: Leading the Charge in Disease Prediction, Prevention, and Immunotherapeutic Mechanistic Understanding.Diabetes care · 2025Review
- Review
- Advances and future perspectives in the treatment and prognosis of type 1 diabetes mellitus.Frontiers in clinical diabetes and healthcare · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
objectiveTo explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As). RESEARCH AND
methodsNext-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.
resultsOral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).
conclusionsThese results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.
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