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Mechanisms of diabetic neuropathy: axon dysfunction
Anders A F Sima1, Weixian Zhang2
1Department of Pathology, Wayne State University, Detroit, MI, USA; Department of Neurology, Wayne State University, Detroit, MI, USA.
Handbook of Clinical Neurology
|November 21, 2014
Summary
Diabetic neuropathy, a common diabetes complication, involves nerve damage. While current therapies are limited, targeting underlying issues like insulin deficiency and hyperglycemia shows promise.
Area of Science:
- Neurology
- Endocrinology
- Metabolic Diseases
Background:
- Diabetic neuropathy is a prevalent complication of diabetes, characterized by sensory loss, pain, and autonomic dysfunction.
- Pathologically, it stems from metabolic abnormalities, primarily insulin deficiency and hyperglycemia.
- Distinct structural changes occur in type 1 DM (insulin deficiency) versus type 2 DM (insulin resistance).
Purpose of the Study:
- To describe sequential neuropathologic changes in diabetic neuropathy.
- To elucidate differences in structural changes between type 1 and type 2 diabetes.
- To explore the impact of metabolic defects on nerve function and potential therapeutic strategies.
Main Methods:
- Review of animal data to detail neuropathologic changes.
- Analysis of metabolic abnormalities underlying diabetic neuropathy.
- Discussion of therapeutic approaches targeting core pathogenetic factors.
Main Results:
- Type 1 DM neuropathy shows more severe axonal atrophy and loss; type 2 DM shows milder axonal involvement and segmental myelin breakdown.
- Metabolic defects significantly impact nerve function across somatic, autonomic, and central nervous systems.
- Experimental therapies targeting polyol-pathway and oxidative stress have yielded limited success.
Conclusions:
- Diabetic neuropathy remains a significant challenge with no universally successful therapy.
- Therapies addressing insulin deficiency and hyperglycemia, such as C-peptide, show therapeutic potential, especially with early intervention.
- Further research into underlying metabolic derangements is crucial for effective treatment development.
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