Pathogenesis of diabetic symmetric distal polyneuropathy (DSDP)
| ▸ Metabolic | Hyperglycaemia leads to overactivity of polyol pathway (via aldose reductase), with secondary depletion of myo-inositol which reduces the concentration of phosphoinositides, leading to low concentrations of diacylglycerol which serves as a second messenger for stimulation of Na-K ATPase. The resulting depletion of Na-K ATPase has been proposed to lead to axonal degeneration and demyelination |
| Advanced glycosylation of endproducts. May lead among other changes to an increase in low density lipoproteins thereby promoting smooth muscle proliferation and atheromatous change in endoneurial vessels | |
| Reduced concentration of nerve growth factors. In particular NGF, insulin-like growth factors (IGF-1 and IGF-2), ciliary neurotrophic factor, and glial derived neurotrophic factor | |
| Increased oxidative stress. This leads to increased lipid peroxidation. Antioxidants such as α lipoic acid may help | |
| Altered fatty acid metabolism. Prostaglandin precursors (especially γ linolenic acid and PGE1) are depleted. PGE1 is a vasodilator with antiplatelet activity and it also inhibits collagen deposition and plays a role in regulating tissue Na-K ATPase | |
| ▸ Vascular | Basement membrane reduplication in vasa nervorum |
| Reduced endoneurial blood flow | |
| Reduced endoneurial oxygen tension |