Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?

Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been f...

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Main Authors: M. C. Perez-Matos, M. C. Morales-Alvarez, C. O. Mendivil
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2017/6943851
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author M. C. Perez-Matos
M. C. Morales-Alvarez
C. O. Mendivil
author_facet M. C. Perez-Matos
M. C. Morales-Alvarez
C. O. Mendivil
author_sort M. C. Perez-Matos
collection DOAJ
description Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.
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spelling doaj-art-e70f69995f77474f97f25391323b71132025-08-20T03:26:10ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/69438516943851Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?M. C. Perez-Matos0M. C. Morales-Alvarez1C. O. Mendivil2School of Medicine, Universidad de Los Andes, Bogotá, ColombiaSchool of Medicine, Universidad de Los Andes, Bogotá, ColombiaSchool of Medicine, Universidad de Los Andes, Bogotá, ColombiaDiabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.http://dx.doi.org/10.1155/2017/6943851
spellingShingle M. C. Perez-Matos
M. C. Morales-Alvarez
C. O. Mendivil
Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
Journal of Diabetes Research
title Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
title_full Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
title_fullStr Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
title_full_unstemmed Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
title_short Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
title_sort lipids a suitable therapeutic target in diabetic neuropathy
url http://dx.doi.org/10.1155/2017/6943851
work_keys_str_mv AT mcperezmatos lipidsasuitabletherapeutictargetindiabeticneuropathy
AT mcmoralesalvarez lipidsasuitabletherapeutictargetindiabeticneuropathy
AT comendivil lipidsasuitabletherapeutictargetindiabeticneuropathy