This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this proposal is to develop, evaluate, and validate surrogate measures of neuropathy progression appropriate to the painful, small fiber neuropathy typical of early diabetes and to investigate the relationship between cutaneous microvascular dysfunction and other microvascular endpoints (retinopathy and nephropathy). We hypothesize that decreased nitric oxide and microvascular injury are important in the initiation of diabetic neuropathy (DN), and abnormal cutaneous microvascular function will precede the development of neuropathy and other microvascular complications. Skin biopsy with measurement of intraepidermal nerve fiber density (IENFD) will be a sensitive marker of subsequent axonal loss and will serve as a useful measure of early DN progression. The project goals are to validate IENFD as a progression measure of mild DN and to correlate cutaneous microvascular dysfunction with severity of small fiber loss and risk of developing microvascular complications.
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