Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

Luis Miguel Román-Pintos, Geannyne Villegas-Rivera, Adolfo Daniel Rodríguez-Carrizalez, Alejandra Guillermina Miranda-Díaz, Ernesto Germán Cardona-Muñoz, Luis Miguel Román-Pintos, Geannyne Villegas-Rivera, Adolfo Daniel Rodríguez-Carrizalez, Alejandra Guillermina Miranda-Díaz, Ernesto Germán Cardona-Muñoz

Abstract

Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

Conflict of interest statement

The authors declare that there are no competing interests.

Figures

Figure 1
Figure 1
Prevalence of DPN by country. Colors represent the percentiles 25, 50, and 75 of epidemiology studies.
Figure 2
Figure 2
Mechanisms of nerve dysfunction induced by hyperglycemia. The description of how inflammation, oxidative stress, and mitochondrial dysfunction contributes to ROS/RNS formation and nerve damage. ∗Paradoxical increase of adiponectin in DPN.

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