<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Neuropathy is one of the most debilitating complications
of both type 1 and type 2 diabetes, with estimates of prevalence
between 50–90% depending on the means of detection.
Diabetic neuropathies are heterogeneous and there is
variable involvement of large myelinated fibers and small,
thinly myelinated fibers. Many of the neuronal abnormalities
in diabetes can be duplicated by experimental depletion
of specific neurotrophic factors, their receptors or their
binding proteins. In experimental models of diabetes there
is a reduction in the availability of these growth factors,
which may be a consequence of metabolic abnormalities,
or may be independent of glycemic control. These neurotrophic
factors are required for the maintenance of the
neurons, the ability to resist apoptosis and regenerative capacity.
The best studied of the neurotrophic factors is nerve
growth factor (NGF) and the related members of the neurotrophin
family of peptides. There is increasing evidence
that there is a deficiency of NGF in diabetes, as well as the
dependent neuropeptides substance P (SP) and calcitonin
gene-related peptide (CGRP) that may also contribute to
the clinical symptoms resulting from small fiber dysfunction.
Similarly, NT3 appears to be important for large fiber
and IGFs for autonomic neuropathy. Whether the observed
growth factor deficiencies are due to decreased synthesis, or
functional, e.g. an inability to bind to their receptor, and/or
abnormalities in nerve transport and processing, remains
to be established. Although early studies in humans on the
role of neurotrophic factors as a therapy for diabetic neuropathy
have been unsuccessful, newer agents and the possibilities
uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate
that neurotrophic factor therapy, specifically targeted
at different nerve fiber populations, might enter the therapeutic
armamentarium.</p>
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Exp Diabesity Res. 2003; 4(4):271-285