Immunohistochemical measurements of nerves and neuropeptides in diabetic skin: relationship to tests of neurological function.
Image-analysis was used to measure nerves immunoreactive to the general neuronal marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin gene-related peptide and vasoactive intestinal polypeptide in standardised leg skin biopsies of three age-matched groups of young subjects: non-diabetic (n = 14), diabetic patients with normal small fibre function ("non-neuropathic", (n = 11) and diabetic patients with abnormal small fibre function ("neuropathic", n = 11). Depletion of nerves and neuropeptides was most marked in the epidermis, where calcitonin gene-related peptide-immunoreactivity was more frequently absent than PGP 9.5-IR in diabetic patients. Epidermal PGP 9.5-IR nerve area and counts were reduced in neuropathic compared with normal subjects (p less than 0.001), as were epidermal calcitonin gene-related peptide nerve counts (p = 0.003). Sweat gland PGP 9.5 and vasoactive intestinal polypeptide, which may be involved in sweat production, showed no diminution in diabetic patients (area: p = 0.160, p = 0.372 by ANOVA). Two diabetic patients showed elevated sweat gland PGP 9.5-IR and three had increased sweat gland vasoactive intestinal polypeptide; this may represent nerve proliferation. In local sweat tests, acetylcholine-stimulated sweat output was associated with increased immunoreactivity, while the sympathetic skin response showed inverse correlations with immunoreactivity. There were no consistent changes with other commonly-used neurophysiological tests. HbA1 correlated negatively with immunohistochemical measurements. Neuropeptide changes were seen in the absence of macro- and microvascular disease, and epidermal nerve depletion occurred in patients with normal thermal thresholds and cardiac autonomic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Levy
D M
DM
Department of Diabetes and Endocrinology, Central Middlesex Hospital, London, UK.
Terenghi
G
G
Gu
X H
XH
Abraham
R R
RR
Springall
D R
DR
Polak
J M
JM
D000328:Adult; D000704:Analysis of Variance; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D003929:Diabetic Neuropathies / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000032:analysis*; D012867:Skin / Q000276:immunology* / Q000294:innervation; D013545:Sweat Glands / Q000276:immunology; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide / Q000032:analysis
D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide