ArticleJournal of biomedical materials research. Part A2021
Advancing continuous subcutaneous insulin infusion in vivo: New insights into tissue challenges.
Article in Journal of biomedical materials research. Part A, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
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.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Immunomodulatory Effects of Insulin-Derived Fibrils from Infusion Pumps: Role of Phenolic Preservatives in Macrophage Activation.Research square · 2026Article
- Insulin preservatives trigger neutrophil extracellular trap formation through SYNE1-mediated nuclear disassembly.bioRxiv : the preprint server for biology · 2026Article
- Immunomodulatory Effects of Insulin-Derived Fibrils from Infusion Pumps: Role of Phenolic Preservatives in Macrophage Activation.bioRxiv : the preprint server for biology · 2026Article
- Exploring humidity effects on polycrystalline human insulin-ligand complexes: preliminary crystallographic insights.Journal of applied crystallography · 2025Article
- Injury to tissue caused by device penetration of the skin triggers formation of extracellular traps.Communications biology · 2025Article
- Phenolic Preservatives Are Not the Sole Cause of Eosinophilic Infiltration at Infusion Pump Sites.Diabetes technology & therapeutics · 2025Article
- Therapeutic Insulin Analogue Concentrations at Infusion Sites Enhanced the Pro-Inflammatory Response and Apoptosis in an In Vitro Macrophage-Material Interaction Model.ACS pharmacology & translational science · 2024Article
- Electrooxidation of Phenol on Polyelectrolyte Modified Carbon Electrodes for Use in Insulin Pump Infusion Sets.Journal of diabetes science and technology · 2024Article
- Mast Cell Deficiency in Mice Attenuates Insulin Phenolic Preservative-Induced Inflammation.Biomedicines · 2023Article
- The Strategies of Development of New Non-Toxic Inhibitors of Amyloid Formation.International journal of molecular sciences · 2023Review
- Insulin Derived Fibrils Induce CytotoxicityJournal of diabetes science and technology · 2023Article
- A pharmacological approach assessing the role of mast cells in insulin infusion site inflammation.Drug delivery and translational research · 2022Article
- Inflammation at Site of Insulin Infusion Diminishes Glycemic Control.Journal of pharmaceutical sciences · 2022Article
- New insight into the importance of formulation variables on parenteral growth hormone preparations: potential effect on the injection-site pain.Frontiers in endocrinology · 2022Review
- Characteristics and morphology of lipohypertrophic lesions in adults with type 1 diabetes with ultrasound screening: an exploratory observational study.BMJ open diabetes research & care · 2021Observational
- Phenolic Preservative Removal from Commercial Insulin Formulations Reduces Tissue Inflammation while Maintaining Euglycemia.ACS pharmacology & translational science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Continuous Subcutaneous Insulin Infusion (CSII) is superior to conventional insulin therapy as it improves glycemic control thus reducing the probability of diabetic complications. Notwithstanding CSII's benefits, insulin dependent diabetic patients rarely achieve optimal glucose control. Moreover, CSII is only FDA approved for 3 days and often fails prematurely for reasons that have not been fully elucidated. We hypothesize that phenolic compounds, such as m-cresol and phenol, which are present in all commercial insulin formulations are responsible for the tissue reaction occurring at the insulin infusion site. This hypothesis was examined with in vitro cell cultures and a mouse air-pouch model to determine cellular and tissue reactions following infusions with saline, phenolic compounds, (i.e., commercial diluent), and insulin. We demonstrated that diluent and insulin were cytotoxic to cells in culture at sub-clinical concentrations (e.g., >1:10 of commercial insulin). Air pouch studies demonstrated that infusion of either diluted insulin or diluent itself induced three to five-fold level of recruited leukocytes as compared to saline. At both 3- and 7-days post infusion, these were predominantly neutrophils and macrophages. We conclude that phenolic compounds in commercial insulin preparations are cell and tissue toxic, which contributes to the failure of effective insulin infusion therapy.
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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.