title: Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin-dependent diabetics--correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy.
abstract: Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests.
authors.affiliation: Department of Internal Medicine, University of L'Aquila, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Properzi
authors.forename: S
authors.initials: S
authors.lastname: Francavilla
authors.forename: G
authors.initials: G
authors.lastname: Poccia
authors.forename: P
authors.initials: P
authors.lastname: Aloisi
authors.forename: X H
authors.initials: XH
authors.lastname: Gu
authors.forename: G
authors.initials: G
authors.lastname: Terenghi
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
mesh_terms: D000293:Adolescent; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism*; D013545:Sweat Glands; D013869:Thiolester Hydrolases / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
chemical_list: D014660:Vasoactive Intestinal Peptide; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide