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Biomedicines
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Novel Biomarker and Treatments for Diabetic Neuropathy
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Novel Biomarker and Treatments for Diabetic Neuropathy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3242

Special Issue Editors

Prof. Dr. Arun V. Krishnan

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Guest Editor
1. School of Clinical Medicine, University of New South Wales Sydney, Kensington, NSW 2033, Australia
2. Department of Neurology, Prince of Wales Hospital, Sydney, NSW 2031, Australia
Interests: diabetic peripheral neuropathy; type 1 diabetes; type 2 diabetes; glucagon-like peptide-1 receptor agonists; metabolic syndrome; in vivo corneal confocal microscopy; nerve ultrasonography; obesity; exercise
Dr. Tushar Issar

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Guest Editor
School of Clinical Medicine, University of New South Wales Sydney, Kensington, NSW 2033, Australia
Interests: diabetic peripheral neuropathy; type 1 diabetes; type 2 diabetes; glucagon-like peptide-1 receptor agonists; metabolic syndrome; in vivo corneal confocal microscopy; nerve ultrasonography; obesity; exercise

Special Issue Information

Dear Colleagues,

We invite researchers to submit original studies for a special edition of Biomedicines focused on diabetic neuropathy. This issue will highlight cutting-edge clinical and preclinical research, including molecular science and animal models, that explore novel therapeutic options. We are particularly interested in studies examining the effects of new and potential treatments on disease mechanisms and patient-related outcomes, as well as research on the role of existing pharmaceuticals in managing diabetic neuropathy. Ultimately, this edition aims to advance therapeutic interventions and improve clinical care for individuals affected by diabetes.

All submissions will undergo peer review, and accepted articles will be published in a high-visibility edition of Biomedicines. We look forward to receiving your contribution to this critical area of medical science.

Prof. Dr. Arun V. Krishnan
Dr. Tushar Issar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diabetic peripheral neuropathy
  • type 1 diabetes
  • type 2 diabetes
  • glucagon-like peptide-1 receptor agonists
  • metabolic syndrome
  • in vivo corneal confocal microscopy
  • nerve ultrasonography
  • obesity
  • exercise

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Published Papers (4 papers)

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Research

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15 pages, 1205 KiB  
Article
Omega-3 Polyunsaturated Fatty Acids (PUFAs) and Diabetic Peripheral Neuropathy: A Pre-Clinical Study Examining the Effect of Omega-3 PUFAs from Fish Oil, Krill Oil, Algae or Pharmaceutical-Derived Ethyl Esters Using Type 2 Diabetic Rats
by Eric Davidson, Oleksandr Obrosov, Lawrence Coppey and Mark Yorek
Biomedicines 2025, 13(7), 1607; https://doi.org/10.3390/biomedicines13071607 - 30 Jun 2025
Viewed by 677
Abstract
Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a [...] Read more.
Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article
(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)
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12 pages, 305 KiB  
Article
Real-World Effectiveness of Different Nutraceutical Formulations on Pain Intensity of Subjects with Diabetic Peripheral Neuropathy: An Observational, Retrospective, Case–Control Study
by Laura Armeli Grigio, Denisa Boci, Giacoma Di Vieste, Gianluca Cassanelli, Oscar Massimiano Epis, Alessandro Viadana, Federico Bertuzzi and Basilio Pintaudi
Biomedicines 2025, 13(6), 1407; https://doi.org/10.3390/biomedicines13061407 - 8 Jun 2025
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Abstract
Background/Objectives. Diabetic peripheral neuropathy is a debilitating disease-related complication with a significant impact on quality of life. Its management represents a therapeutic challenge. Antioxidant agents such as α-lipoic acid, N-acetyl cysteine, and glutatione may be useful treatment strategies. Methods. A real-world, [...] Read more.
Background/Objectives. Diabetic peripheral neuropathy is a debilitating disease-related complication with a significant impact on quality of life. Its management represents a therapeutic challenge. Antioxidant agents such as α-lipoic acid, N-acetyl cysteine, and glutatione may be useful treatment strategies. Methods. A real-world, observational, retrospective, case–control study involving consecutive subjects with type 2 diabetes with diabetic peripheral neuropathy was performed. Participants who were supplemented with three different formulations for 12 weeks (high-dose α-lipoic acid (800 mg); low-dose α-lipoic acid (100 mg) plus glutathione (200 mg) plus Vitamin D (800 IU); N-acetyl cysteine (600 mg) plus glutathione (200 mg) plus Vitamin D (800 IU)) were compared with a non-treated control group. Questionnaires aimed at investigating the degree of disability and quality of life were administered. The primary endpoint was the change in neuropathic pain intensity measured by the Numerical Rating Scale (NRS). Results. Among 750 consecutive screened subjects with type 2 diabetes, 98 (13%) had diabetic neuropathy (mean age 66.7 ± 7.6 years, diabetes duration 11.3 ± 6.7 years, HbA1c 8.1 ± 1.5%, 43.8% insulin-treated). When comparing the differences between treatment groups in the changes in individual questionnaire scores between baseline and follow-up, all three supplements showed significant reductions compared to the control group in the NRS scale scores. No side effects have been reported during the study. Conclusions. As well as lipoic acid, other substances with specific activity on the genesis of neuropathic pain, such as N-acetyl cysteine and glutathione, have proved effective in reducing the intensity of pain. Full article
(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)
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Review

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29 pages, 1685 KiB  
Review
Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy
by Corina Andrei, Oana Cristina Șeremet, Ciprian Pușcașu and Anca Zanfirescu
Biomedicines 2025, 13(7), 1709; https://doi.org/10.3390/biomedicines13071709 - 13 Jul 2025
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Abstract
Diabetic neuropathy (DN) remains a major clinical burden, characterized by progressive sensory dysfunction, pain, and impaired quality of life. Despite the available symptomatic treatments, there is a pressing need for disease-modifying therapies. In recent years, preclinical research has highlighted the potential of repurposed [...] Read more.
Diabetic neuropathy (DN) remains a major clinical burden, characterized by progressive sensory dysfunction, pain, and impaired quality of life. Despite the available symptomatic treatments, there is a pressing need for disease-modifying therapies. In recent years, preclinical research has highlighted the potential of repurposed pharmacological agents, originally developed for other indications, to target key mechanisms of DN. This narrative review examines the main pathophysiological pathways involved in DN, including metabolic imbalance, oxidative stress, neuroinflammation, ion channel dysfunction, and mitochondrial impairment. A wide array of repurposed drugs—including antidiabetics (metformin, empagliflozin, gliclazide, semaglutide, and pioglitazone), antihypertensives (amlodipine, telmisartan, aliskiren, and rilmenidine), lipid-lowering agents (atorvastatin and alirocumab), anticonvulsants (topiramate and retigabine), antioxidant and neuroprotective agents (melatonin), and muscarinic receptor antagonists (pirenzepine, oxybutynin, and atropine)—have shown promising results in rodent models, reducing neuropathic pain behaviors and modulating underlying disease mechanisms. By bridging basic mechanistic insights with pharmacological interventions, this review aims to support translational progress toward mechanism-based therapies for DN. Full article
(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)
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Other

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21 pages, 2230 KiB  
Systematic Review
Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies
by Prajna Vidyasagar, Scott F. Farrell, Luisa Holguin Colorado, Samantha Dando and Katie Edwards
Biomedicines 2025, 13(7), 1675; https://doi.org/10.3390/biomedicines13071675 - 8 Jul 2025
Viewed by 681
Abstract
Background/Objectives: Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density [...] Read more.
Background/Objectives: Painful diabetic peripheral neuropathy (pDPN) significantly impacts quality of life, yet its diagnosis remains challenging due to reliance on subjective pain reports and limited objective biomarkers. This meta-analysis evaluated corneal nerve morphology parameters; corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), and corneal nerve branch density (CNBD), measured through in vivo confocal microscopy (IVCM), as potential tools for differentiating painful and painless forms of diabetic neuropathy. Methods: A systematic review was performed comparing corneal nerve morphology across four groups: painful diabetic neuropathy (pDPN), non-painful diabetic neuropathy (npDPN), diabetes without neuropathy (DPN-), and healthy controls. Literature search extended over MEDLINE, EMBASE, Web of Science, and Cochrane Library, focusing on studies published since 2000. Study quality was assessed using the Newcastle–Ottawa Scale, while evidence certainly followed GRADE guidelines. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs) for CNFL, CNFD, and CNBD. Results: Seven observational studies comprising 803 participants (213 pDPN, 275 npDPN, 99 DPN-, and 216 controls) revealed no significant differences between pDPN and npDPN groups in CNFL (MD = 0.79, 95% CI −0.64 to 2.22), CNFD (MD = 1.67, 95% CI −0.14 to 3.47), or CNBD (MD = 1.84, 95% CI −4.31 to 7.98). However, all metrics were markedly reduced in pDPN compared to DPN- and healthy controls. Conclusions: While effective in identifying diabetic neuropathy, common corneal nerve morphology parameters cannot reliably distinguish pDPN from npDPN. This highlights the need for research into mechanisms like central sensitization, inflammation, and micro-neuromas, which could refine diagnostic and therapeutic approaches for pDPN. Full article
(This article belongs to the Special Issue Novel Biomarker and Treatments for Diabetic Neuropathy)
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