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Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve : Implications for diabetic neuropathy

Mohseni, Simin; Badii, Medeea; Kylhammar, Axel; Thomsen, Niels O.B. LU ; Eriksson, Karl Fredrik LU ; Malik, Rayaz A.; Rosén, Ingmar LU and Dahlin, Lars B. LU (2017) In Brain and Behavior 7(8).
Abstract

Objectives: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Patients and Methods: Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM. Results: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline.... (More)

Objectives: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Patients and Methods: Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM. Results: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. Conclusions: We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
autophagy, diabetes, endoneurial capillary, impaired glucose tolerance, morphometry, peripheral neuropathy
in
Brain and Behavior
volume
7
issue
8
publisher
John Wiley & Sons
external identifiers
  • scopus:85023185758
ISSN
2157-9032
DOI
language
English
LU publication?
yes
id
514b6b2b-dfc7-439b-82fd-effe0922ae97
date added to LUP
2018-01-25 12:05:31
date last changed
2018-05-29 11:39:00
@article{514b6b2b-dfc7-439b-82fd-effe0922ae97,
  abstract     = {<p>Objectives: The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy. Patients and Methods: Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM. Results: Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher g-ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline. Conclusions: We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy.</p>},
  articleno    = {e00763},
  author       = {Mohseni, Simin and Badii, Medeea and Kylhammar, Axel and Thomsen, Niels O.B. and Eriksson, Karl Fredrik and Malik, Rayaz A. and Rosén, Ingmar and Dahlin, Lars B.},
  issn         = {2157-9032},
  keyword      = {autophagy,diabetes,endoneurial capillary,impaired glucose tolerance,morphometry,peripheral neuropathy},
  language     = {eng},
  month        = {08},
  number       = {8},
  publisher    = {John Wiley & Sons},
  series       = {Brain and Behavior},
  title        = {Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve : Implications for diabetic neuropathy},
  url          = {http://dx.doi.org/},
  volume       = {7},
  year         = {2017},
}