Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
J Diabetes Res
; 2017: 6943851, 2017.
Article
em En
| MEDLINE
| ID: mdl-28191471
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropatias Diabéticas
/
Metabolismo dos Lipídeos
/
Lipídeos
/
Hipolipemiantes
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Diabetes Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Colômbia
País de publicação:
Reino Unido