title: Surrogate markers of small fiber damage in human diabetic neuropathy.
abstract: Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied. They underwent a punch skin biopsy to quantify IENFs and CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and branch length showed a progressive reduction with increasing severity of neuropathy, which was significant in patients with mild, moderate, and severe neuropathy. CCM also showed a progressive reduction in corneal nerve fiber density (CNFD) and branch density, but the latter was significantly reduced even in diabetic patients without neuropathy. Both IENFD and CNFD correlated significantly with cold detection and heat as pain thresholds. Intraepidermal and corneal nerve fiber lengths were reduced in patients with painful compared with painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify small nerve fiber damage in diabetic patients. However, CCM quantifies small fiber damage rapidly and noninvasively and detects earlier stages of nerve damage compared with IENF pathology. This may make it an ideal technique to accurately diagnose and assess progression of human diabetic neuropathy.
authors.affiliation: Division of Cardiovascular Medicine, University of Manchester, Manchester Diabetes Centre and Manchester Royal Infirmary, Manchester, UK.
authors.forename: Cristian
authors.initials: C
authors.lastname: Quattrini
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.forename: Maria
authors.initials: M
authors.lastname: Jeziorska
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kallinikos
authors.forename: Solomon
authors.initials: S
authors.lastname: Tesfaye
authors.forename: Joanne
authors.initials: J
authors.lastname: Finnigan
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.forename: Andrew J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: Nathan
authors.initials: N
authors.lastname: Efron
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers