Trial reportDiabetes care2016
Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes.
Trial report in Diabetes care, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical parameters and emerging biomarkers of partial remission in pediatric type 1 diabetes: a systematic review.Frontiers in endocrinology · 2026Pooled it
- Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.Cell reports. Medicine · 2023Trial
- Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.Science translational medicine · 2021Trial
- Impact of Body Size on Preclinical Type 1 Diabetes Development and Progression.Diabetes care · 2026Review
- BMI Normalization Is Associated With Lower Risk of Progression to Type 1 Diabetes, Primarily in Youth.Diabetes care · 2026Article
- Biomarkers of partial remission in paediatric type 1 diabetes: β-cell stress, immune-metabolic remodelling, and translational priorities-a narrative review.Translational pediatrics · 2026Review
- Citrullination and Deamidation in Type 1 Diabetes: Linking Beta Cell Stress to Neoantigen-Driven Autoimmunity.Immunological reviews · 2026Review
- From Disposal to Display: Crinophagy as a β-Cell Source of Neoantigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Islet Autotransplant Recipients Have Elevated Proinsulin-to-C-Peptide Ratios Supporting Metabolic Stress as a Cause of Islet Attrition.Diabetes · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Toward Personalized Medicine in Type 1 Diabetes: Understanding How Patient Heterogeneity Influences Therapeutic Efficacy.Diabetes, obesity & metabolism · 2026Review
- Article
- Effect of temperature and preservative selection on C-peptide degradation in randomly voided urine.Journal of clinical & translational endocrinology · 2026Article
- Natural history of a pediatric cohort with islet autoantibody positivity: a single-center retrospective cohort study.Journal of the Endocrine Society · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Toward Disease-Modifying Therapies in Type 1 Diabetes: Focus on Teplizumab.Diabetes care · 2026Review
- Comparison of Islet Function in People With Different Glucose Metabolic States.Endocrine, metabolic & immune disorders drug targets · 2026Article
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.Diabetes, obesity & metabolism · 2025Article
46 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
objectiveWe tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND
methodsFasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels.
resultsAlthough absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05).
conclusionsThese data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase.
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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.