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Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

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Abstract

Aims/hypothesis

We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS).

Methods

The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy.

Results

In diabetic patients median nerve distal motor latency was prolonged (p < 0.05 vs non-diabetic patients), PIN myelinated fibre density (p < 0.05), fibre area (p < 0.0001) and axon area (p < 0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p < 0.0001) and unmyelinated axon density (p < 0.0001) were increased and the axon diameter was reduced (p < 0.0001). Endoneurial capillary basement membrane area was increased (p < 0.0001) in diabetic patients, but endothelial cell number was increased (p < 0.01) and luminal area was reduced (p < 0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p < 0.05) and its receptors VEGFR-1 (p < 0.01) and VEGFR-2 (p < 0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology.

Conclusions/interpretation

This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.

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Abbreviations

Ab:

Antibody

CTS:

Carpal tunnel syndrome

DCTS:

Diabetic patients with CTS

DML:

Distal motor latency

fSNCV:

Fractionated measurement of antidromic sensory conduction velocity

HIF-1α:

Hypoxia-inducible factor 1α

MNFD:

Myelinated nerve fibre density

NCTS:

Non-diabetic patients with CTS

PIN:

Posterior interosseus nerve

USCP:

Unassociated Schwann cell profile

VEGF:

Vascular endothelial growth factor

VEGFR:

VEGF receptor

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Acknowledgements

The study was supported by the Swedish Research Council (Medicine; No. 5188), the Medical Faculty, Lund, Diabetesföreningen i Malmö med omnejd, Skåne University Hospital, Malmö and Region Skåne (ALF).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

MAM, MA, RA, MJ and AA made substantial contributions to the acquisition, analysis and interpretation of data and drafted the article. NOBT and LBD made substantial contributions to the conception and design of the study and the acquisition, analysis and interpretation of data and revised the article critically for important intellectual content. RAM made substantial contributions to the conception and design of the study, analysis and interpretation of data and drafting and revising the article critically for important intellectual content. All authors gave final approval for the version to be published. RAM is the guarantor of this work.

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Authors and Affiliations

  1. Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, UK

    Moaz A. Mojaddidi, Mohammed S. Ahmed, Razwan Ali, Maria Jeziorska, Ahmed Al-Sunni & Rayaz A. Malik

  2. Department of Physiology, Taibah University, Almadinah Almunawwarah, Saudi Arabia

    Moaz A. Mojaddidi

  3. Department of Physiology, University of Dammam, College of Medicine, Dammam, Saudi Arabia

    Ahmed Al-Sunni

  4. Department of Hand Surgery, Malmö University Hospital, Malmö, Sweden

    Niels O. B. Thomsen & Lars B. Dahlin

  5. Department of Clinical Sciences Malmö – Hand Surgery, Lund University, Malmö, Sweden

    Lars B. Dahlin

  6. Weill Cornell Medical College, Doha, Quatar

    Rayaz A. Malik

Authors
  1. Moaz A. Mojaddidi
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  2. Mohammed S. Ahmed
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  3. Razwan Ali
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  8. Rayaz A. Malik
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Correspondence to Rayaz A. Malik.

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Mojaddidi, M.A., Ahmed, M.S., Ali, R. et al. Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome. Diabetologia 57, 1711–1719 (2014). https://doi.org/10.1007/s00125-014-3271-3

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