Pathophysiology of Diabetic Polyneuropathy (DPN)1-4


The pathophysiology of DPN is not yet fully understood, however, some consequences of diabetes that might contribute to this phenomenon have been elucidated.

A hallmark characteristic of diabetes is hyperglycaemia, which is caused by insufficient glucose uptake and conversion as a consequence of diminished insulin production, as in type 1 diabetes, or due to impaired responsiveness to insulin, as in type 2 diabetes.

The consequences of hyperglycaemia include glucose secretion by the kidneys, upregulation of the polyol pathway, and the use of alternative molecules such as fatty acids and peptides as sources of energy.1

The products of the polyol pathway, and to some extent glucose itself, cause non-enzymatic glycation of proteins, nucleotides and lipids, and lead to the formation of advanced glycation end-products (or AGEs). The polyol pathway, non-enzymatic glycation and AGE formation are all suggested to contribute to microvascular dysfunction and oxidative stress which eventually cause nerve cell death and the onset of DPN.

 

References
1 Sima AA et al. Diabetic neuropathy differs in type 1 and type 2 diabetes. Ann N Y Acad Sci. 2006; 1084:235-49.
2 Chung SSM et al. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol. 2003; 14(3):233-36.
3 Thornalley PJ. Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. Int Rev Neurobiol. 2002; 50:37-57.
4 Wada R et al. Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci. 2005; 1043:598-604.