ArticleDiabetologia2023
High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 19 citations in OpenAlex.
- Effect of fenofibrate on residual beta cell function in adults and adolescents with newly diagnosed type 1 diabetes: a randomised clinical trial.Diabetologia · 2025Trial
- Impact of Body Size on Preclinical Type 1 Diabetes Development and Progression.Diabetes care · 2026Review
- Biomarkers of partial remission in paediatric type 1 diabetes: β-cell stress, immune-metabolic remodelling, and translational priorities-a narrative review.Translational pediatrics · 2026Review
- Oxidative Stress Biomarkers in Pediatric and Early-Stage Type 1 Diabetes: Toward Redox Phenotyping.Antioxidants (Basel, Switzerland) · 2026Review
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Continuous glucose monitoring as a tool in early-stage type 1 diabetes.Diabetologia · 2026Review
- Failure of Hepatic Insulin Clearance via CEACAM1-Mediated Endocytosis: The Missing Physiological Link Between Proinsulin Misfolding, Hyperinsulinemia, and Metabolic Complications in Type 2 Diabetes, Obesity, and NAFLD.Problemy endokrinologii · 2026Review
- Teplizumab in Stage 2 Type 1 Diabetes: Clinical Practice Experience on Feasibility in 3 Adult Patients.Diabetes, obesity & metabolism · 2026Article
- Stratifying the Rate of Disease Progression by Progression Likelihood Scores in Children and Adolescents With Stage 1 and Stage 2 Type 1 Diabetes in Germany.Diabetes care · 2026Article
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 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
- Artificial intelligence-driven therapeutics for disease modification in type 1 diabetes: a digital public health and clinical translation framework.Frontiers in public health · 2026Review
- Extending the Eisenbarth Model: Stage 0 as a Provisional Framework for Early Risk Stratification and Prevention in Type 1 Diabetes.Journal of diabetes research · 2026Review
- An Antibody Cocktail-Based Immunoaffinity-LC-MS Method Enabled Ultra-Sensitive and Robust Quantification of Circulating Proinsulin Proteoforms and C-Peptide.Analytical chemistry · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Morphological and functional alterations in type 2 diabetes pancreata assessed with MRI-based metrics and [Frontiers in endocrinology · 2025Article
- Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes.Frontiers in immunology · 2025Review
- Quantitative analysis of islet prohormone convertase 1/3 expression in human pancreas donors with diabetes.Diabetologia · 2024Article
- Inhibition of the eukaryotic initiation factor-2α kinase PERK decreases risk of autoimmune diabetes in mice.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
aims/hypothesisTractable precision biomarkers to identify immunotherapy responders are lacking in type 1 diabetes. We hypothesised that proinsulin:C-peptide (PI:C) ratios, a readout of beta cell stress, could provide insight into type 1 diabetes progression and responses to immunotherapy.
methodsIn this post hoc analysis, proinsulin and C-peptide levels were determined in baseline serum samples from 63 participants with stage 2 type 1 diabetes in the longitudinal TrialNet Teplizumab Prevention Study (n=41 in the teplizumab arm; n=22 in the placebo arm). In addition, previously tested demographic, C-peptide, glucose and proinsulin data were used for the new data analyses. The ratio of intact (unprocessed) proinsulin to C-peptide was analysed and relationships with progression to stage 3 diabetes were investigated.
resultsElevated baseline PI:C was strongly associated with more rapid progression of diabetes in both the placebo and teplizumab treatment groups, but teplizumab abrogated the impact of high pre-treatment PI:C on type 1 diabetes progression. Differential responses of drug treatment in those with high vs low PI:C ratios were independent of treatment effects of teplizumab on the PI:C ratio or on relevant immune cells. CONCLUSIONS/
interpretationHigh pre-treatment PI:C identified individuals with stage 2 type 1 diabetes who were exhibiting rapid progression to stage 3 disease and who displayed benefit from teplizumab treatment. These data suggest that readouts of active disease, such as PI:C ratio, could serve to identify optimal candidates or timing for type 1 diabetes disease-modifying therapies.
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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.