Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy

Xiaoli Hu, Christian Selmer Buhl, Marie Balle Sjogaard, Karoline Schousboe, Hatice Isik Mizrak, Huda Kufaishi, Troels Staehelin Jensen, Christian Stevns Hansen, Knud Bonnet Yderstræde, Ming-Dong Zhang, Patrik Ernfors, Jens Randel Nyengaard, Pall Karlsson*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


AIMS/HYPOTHESIS: Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes.

METHODS: Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres.

RESULTS: There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures.

CONCLUSIONS/INTERPRETATION: Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.

Original languageEnglish
Pages (from-to)2332-2345
Number of pages14
Publication statusPublished - Dec 2023


  • Diabetic polyneuropathy
  • Neuropathic pain
  • Nociceptive Schwann cell
  • Skin punch biopsy
  • Type 1 diabetes
  • Humans
  • Schwann Cells/pathology
  • Nerve Fibers/pathology
  • Peripheral Nerves/pathology
  • Diabetes Mellitus, Type 1/complications
  • Diabetic Neuropathies


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