Diabetes causes neuropathy primarily due to prolonged high blood glucose levels (hyperglycemia), which damage nerves and the small blood vessels that supply them with oxygen and nutrients. This leads to nerve fiber degeneration, impaired nerve function, and nerve damage. Several key mechanisms contribute to this process:
- Metabolic changes from hyperglycemia cause increased oxidative stress, production of free radicals, and impaired energy production in nerve cells. This leads to cellular damage and nerve dysfunction.
- Activation of the polyol pathway (sorbitol accumulation) and formation of advanced glycation end-products (AGEs) damage nerve proteins and impair their function.
- Microvascular injury affects the small blood vessels supplying the nerves, causing reduced blood flow, ischemia, and oxygen deprivation to nerves.
- A pro-inflammatory state with release of cytokines and immune cell infiltration further damages nerve tissue.
- Dysfunction in nerve repair mechanisms and mitochondrial damage also contribute.
Overall, the combined effect of metabolic stress, vascular injury, inflammation, and impaired nerve maintenance leads to peripheral nerve damage and diabetic neuropathy, especially in long-standing diabetes with poor blood sugar control.
