Observational studyJCI insight2018
β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis.
Observational study in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00097292 (TrialNet Pathway to Prevention of T1D), which is not on this map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
TrialNet Pathway to Prevention of T1D
Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it.
- American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022Guideline
- Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.Science translational medicine · 2021Trial
- Trial
- Shared non-HLA genetic architecture across diverse ancestries links insulin secretion and resistance to type 1 diabetes.Diabetologia · 2026Article
- Syntaxin-4, a key exocytosis mediating protein, shows heterogeneous expression in insulin-positive cells of human donors with new-onset and longer duration of type 1 diabetes: comparison with non-diabetic autoantibody-positive and -negative donors.Journal of molecular histology · 2026Article
- Continuous glucose monitoring as a tool in early-stage type 1 diabetes.Diabetologia · 2026Review
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes.Cell reports · 2026Article
- Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles.Cell reports. Medicine · 2026Article
- Harnessing exosomal long non-coding RNAs as a new frontier for molecular diagnostics and therapeutics in diabetes mellitus.Cell communication and signaling : CCS · 2026Review
- Toward Disease-Modifying Therapies in Type 1 Diabetes: Focus on Teplizumab.Diabetes care · 2026Review
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Relevance of Quantitative Measures of Beta-Cell Function in Clinical Practice.Hormone research in paediatrics · 2026Review
- Single-Islet Proteomics Maps Pseudo-Temporal Islet Immune Responses and Dysfunction in Stage 1 Type 1 Diabetes.bioRxiv : the preprint server for biology · 2025Article
- Article
- Pancreatic Ultrasound Features at Diagnosis of Type 1 Diabetes: Age-Related Differences in Children.Journal of clinical medicine · 2025Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- Emerging Biomarkers and Nanobiosensing Strategies in Diabetes.Biosensors · 2025Review
- Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians.Diabetes, obesity & metabolism · 2025Review
- Type 1 diabetes presenting in adults: Trends, diagnostic challenges and unique features.Diabetes, obesity & metabolism · 2025Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundThe duration and patterns of β cell dysfunction during type 1 diabetes (T1D) development have not been fully defined.
methodsMetabolic measures derived from oral glucose tolerance tests (OGTTs) were compared between autoantibody-positive (aAb+) individuals followed in the TrialNet Pathway to Prevention study who developed diabetes after 5 or more years or less than 5 years of longitudinal follow-up (Progressors≥5, n = 75; Progressors<5, n = 474) and 144 aAb-negative (aAb-) relatives.
resultsMean age at study entry was 15.0 ± 12.6 years for Progressors≥5; 12.0 ± 9.1 for Progressors<5; and 16.3 ± 10.4 for aAb- relatives. At baseline, Progressors≥5 already exhibited significantly lower fasting C-peptide (P < 0.01), C-peptide AUC (P < 0.001), and early C-peptide responses (30- to 0-minute C-peptide; P < 0.001) compared with aAb- relatives, while 2-hour glucose (P = 0.03), glucose AUC (<0.001), and Index60 (<0.001) were all higher. Despite significant baseline impairment, metabolic measures in Progressors≥5 were relatively stable until 2 years prior to T1D diagnosis, when there was accelerated C-peptide decline and rising glycemia from 2 years until diabetes diagnosis. Remarkably, patterns of progression within 3 years of diagnosis were nearly identical between Progressors≥5 and Progressors<5.
conclusionThese data provide insight into the chronicity of β cell dysfunction in T1D and indicate that β cell dysfunction may precede diabetes diagnosis by more than 5 years in a subset of aAb+ individuals. Even among individuals with varying lengths of aAb positivity, our findings indicate that patterns of metabolic decline are uniform within the last 3 years of progression to T1D.
trial registrationClinicaltrials.gov NCT00097292.
fundingThe Type 1 Diabetes TrialNet Study Group is a clinical trials network currently funded by the NIH through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Juvenile Diabetes Research Foundation.
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What OpenQuestion holds
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.