Evidence map›Paper›PMID 36445944›Full record

ArticleDiabetes2023

Oral Peroxisome Proliferator-Activated Receptor-α Agonist Enhances Corneal Nerve Regeneration in Patients With Type 2 Diabetes.

Calesta Hui Yi Teo, Molly Tzu-Yu Lin, Isabelle Xin Yu Lee, Siew-Kwan Koh, Lei Zhou, Dylan Shaoying Goh, Hyungwon Choi, Hiromi Wai Ling Koh, Amanda Yun Rui Lam, Paik Shia Lim and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  6. Diabetic keratopathy and nuclear proteins (Review).Molecular medicine reports · 2026
    Review
  7. Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
    Review
  8. Article
  9. Fenofibrate and Diabetic Retinopathy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
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  18. Article
  19. Hypoglycemic Effects and Quality Marker Screening ofMolecules (Basel, Switzerland) · 2024
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Calesta Hui Yi TeoYong Loo Lin School of Medicine, National University of Singapore, Singapore.ORCID 0000-0002-7611-3664
Molly Tzu-Yu LinTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore.
Isabelle Xin Yu LeeTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore.
Siew-Kwan KohOcular Proteomic Group, Singapore Eye Research Institute, Singapore.
Lei ZhouOcular Proteomic Group, Singapore Eye Research Institute, Singapore.
Dylan Shaoying GohDepartment of Pharmacy, National University of Singapore, Singapore.
Hyungwon ChoiDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hiromi Wai Ling KohDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Amanda Yun Rui LamDepartment of Endocrinology, Singapore General Hospital, Singapore.
Paik Shia LimDepartment of Pharmacy, Singapore General Hospital, Singapore.
Jodhbir S MehtaTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore.
Jean-Paul KovalikProgram in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore.
Thomas M CoffmanProgram in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore.
Hong Chang TanDepartment of Endocrinology, Singapore General Hospital, Singapore.
Yu-Chi LiuTissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore.ORCID 0000-0001-5408-0382
National University of Singapore · SGSingapore Eye Research Institute · SGSingapore General Hospital · SGDuke-NUS Medical School · SGSingapore National Eye Center · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic corneal neuropathy (DCN) is a common complication of diabetes. However, there are very limited therapeutic options. We investigated the effects of a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, fenofibrate, on 30 patients (60 eyes) with type 2 diabetes. On in vivo confocal microscopy evaluation, there was significant stimulation of corneal nerve regeneration and a reduction in nerve edema after 30 days of oral fenofibrate treatment, as evidenced by significant improvement in corneal nerve fiber density (CNFD) and corneal nerve fiber width, respectively. Corneal epithelial cell morphology also significantly improved in cell circularity. Upon clinical examination, fenofibrate significantly improved patients' neuropathic ocular surface status by increasing tear breakup time along with a reduction of corneal and conjunctival punctate keratopathy. Tear substance P (SP) concentrations significantly increased after treatment, suggesting an amelioration of ocular surface neuroinflammation. The changes in tear SP concentrations was also significantly associated with improvement in CNFD. Quantitative proteomic analysis demonstrated that fenofibrate significantly upregulated and modulated the neurotrophin signaling pathway and linolenic acid, cholesterol, and fat metabolism. Complement cascades, neutrophil reactions, and platelet activation were also significantly suppressed. Our results showed that fenofibrate could potentially be a novel treatment for patients with DCN.

Indexed as

Diabetes Mellitus, Type 2Diabetic NeuropathiesFenofibrateCorneaHumansHypoglycemic AgentsMicroscopy, ConfocalPPAR alphaProteomicsFenofibrateHypoglycemic AgentsPPAR alpha

Identifiers

PMID36445944
PMCPMC10281232
OpenAlexW4310351848

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.