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Evaluation of small nerve fiber dysfunction in type 2 diabetes

Ekman, Linnéa LU ; Thrainsdottir, Soley LU ; Englund, Elisabet LU ; Thomsen, Niels LU ; Rosén, Ingmar LU ; Hazer Rosberg, Derya Burcu LU ; Petersson, Jesper LU ; Eriksson, Karl Fredrik LU and Dahlin, Lars B. LU (2019) In Acta Neurologica Scandinavica
Abstract

Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including... (More)

Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
diabetes mellitus type 2, diabetic neuropathies, inter-rater reliability, intraepidermal nerve fiber density, skin punch biopsy
in
Acta Neurologica Scandinavica
publisher
Wiley-Blackwell
external identifiers
  • pmid:31549387
  • scopus:85074036269
ISSN
0001-6314
DOI
10.1111/ane.13171
language
English
LU publication?
yes
id
6e6f8428-339e-416a-95a3-a378498dc8f1
date added to LUP
2019-11-06 12:16:08
date last changed
2019-11-25 09:35:33
@article{6e6f8428-339e-416a-95a3-a378498dc8f1,
  abstract     = {<p>Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.</p>},
  author       = {Ekman, Linnéa and Thrainsdottir, Soley and Englund, Elisabet and Thomsen, Niels and Rosén, Ingmar and Hazer Rosberg, Derya Burcu and Petersson, Jesper and Eriksson, Karl Fredrik and Dahlin, Lars B.},
  issn         = {0001-6314},
  language     = {eng},
  month        = {09},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Neurologica Scandinavica},
  title        = {Evaluation of small nerve fiber dysfunction in type 2 diabetes},
  url          = {http://dx.doi.org/10.1111/ane.13171},
  doi          = {10.1111/ane.13171},
  year         = {2019},
}