title: Lipids: A Suitable Therapeutic Target in Diabetic Neuropathy?
abstract: 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.
authors.affiliation: School of Medicine, Universidad de Los Andes, Bogotá, Colombia.
authors.forename: M C
authors.initials: MC
authors.lastname: Perez-Matos
authors.affiliation: School of Medicine, Universidad de Los Andes, Bogotá, Colombia.
authors.forename: M C
authors.initials: MC
authors.lastname: Morales-Alvarez
authors.affiliation: School of Medicine, Universidad de Los Andes, Bogotá, Colombia; Fundación Santa Fe de Bogotá, Department of Internal Medicine, Section of Endocrinology, Bogotá, Colombia.
authors.forename: C O
authors.identifier: 0000-0001-5546-4206
authors.initials: CO
authors.lastname: Mendivil
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood*
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids