ArticleDiabetologia2021
Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy.
Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.
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Who cites it
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Corneal Confocal Microscopy and Skin Biopsy to Differentiate Painful From Painless Diabetic Neuropathy: A Systematic Review With Multiple Meta-Analyses.European journal of neurology · 2026Pooled it
- [The EAN-NeuPSIG guideline on the diagnosis of neuropathic pain-a summary].Schmerz (Berlin, Germany) · 2026Guideline
- Review
- Review
- Corneal Nerve Morphology in Painful Diabetic Neuropathy: A Meta-Analysis of In Vivo Confocal Microscopy Studies.Biomedicines · 2025Review
- PCSK9 deficiency promotes the development of peripheral neuropathy.JCI insight · 2025Article
- The intrinsic reason why complementary tests (clinical neurophysiology, neuroimaging, skin biopsy) cannot establish the diagnosis of neuropathic pain.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy.Diabetologia · 2023Article
- Diabetic Peripheral Neuropathy.Handbook of experimental pharmacology · 2022Article
- Involvement of Cutaneous Sensory Corpuscles in Non-Painful and Painful Diabetic Neuropathy.Journal of clinical medicine · 2021Article
- Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management.Brain : a journal of neurology · 2021Review
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
aims/hypothesisDistal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes.
methodsA total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes (n = 45); participants with type 2 diabetes without DSP (DSP-; n = 31); and participants with evidence of DSP (DSP+; n = 173); the last were further separated into painless DSP+ (n = 74) and painful DSP+ (n = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 μm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres.
resultsMedian (IQR) IENFD (fibres/mm) was: 6.7 (5.2-9.2) for healthy control participants; 6.2 (4.4-7.3) for DSP-; 1.3 (0.5-2.2) for painless DSP+; and 0.84 (0.4-1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants (p < 0.001); however, there was no difference between DSP- and painless DSP+ participants, or between painless DSP+ and painful DSP+ participants. The axonal swelling ratio correlated weakly with HbA CONCLUSIONS/
interpretationIn individuals with type 2 diabetes where IENFD is >1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early marker of sensory nerve injury in type 2 diabetes.
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