Table 6

Pathogenesis of diabetic symmetric distal polyneuropathy (DSDP)

▸ MetabolicHyperglycaemia 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
▸ VascularBasement membrane reduplication in vasa nervorum
Reduced endoneurial blood flow
Reduced endoneurial oxygen tension