DN is a common complication of diabetes that often is associated both with considerable morbidity and mortality. The epidemiology and natural history of DN is clouded with uncertainty, largely due to confusion regarding the definition and measurement of this disorder.

The recent resurgence of interest in the vascular hypothesis, oxidative stress, the neurotrophic hypothesis, and the possibility of the role of autoimmunity have opened up new avenues of investigation for therapeutic intervention. Paralleling our increased understanding of the pathogenesis of DN, there must be refinements in our ability to measure quantitatively the different types of defects that occur in this disorder, so that appropriate therapies can be targeted to specific fiber types. These tests must be validated and standardized to allow comparability between studies and a more meaningful interpretation of study results. Our ability to manage successfully the many different manifestations of DN depends ultimately on our success in uncovering the pathogenic processes underlying this disorder.