Causative factors include persistent hyperglycemia, microvascular insufficiency, oxidative and nitrosative stress, defective neurotrophism, and autoimmune-mediated nerve destruction Figure 1 summarizes our current view of the pathogenesis of DN (15). Detailed discussion of the different theories is beyond the scope of this review and the reader is referred to several excellent recent reviews. However, DN is a heterogeneous group of conditions with widely varying pathology, suggesting differences in pathogenic mechanisms for the different clinical syndromes. Recognition of the clinical homologue of these pathologic processes is the first step in achieving the appropriate form of intervention.

Figure 1. Pathogenesis of diabetic neuropathies: Modified from Vinik et al . Ab, antibody; AGE, advance glycation end products; C¢, complement; DAG, diacylglycerol; ET, endothelin; EDHF, endothelium-derived hyperpolarizing factor; GF, growth factor; IGF; insulin-like growth factor; NFkB, nuclear factor kB; NGF, nerve growth factor; NO, nitric oxide; NT3, neurotropin 3; PKC, protein kinase C; PGI2, prostaglandin I2; ROS, reactive oxygen species; TRK, tyrosine kinase .