Evaluation of diabetic neuropathy through the quantitation of cutaneous nerves

The significance and usefulness of immunohistochemically quantitated cutaneous nerves in the evaluation of diabetic neuropathy was examined in biopsied skins of the calf from healthy subjects (n=12) and non-insulin dependent diabetic patients (n=32) with diabetic sensory neuropathy. Skin samples were immunostained with antibodies against protein gene product (PGP) 9.5, a pan-axonal marker. A quantitative analysis to determine nerve fiber (NF) number and nerve lengths (NLs) was performed on nerve fibers of the epidermis and the dermis and on nerves surrounding sweat glands. Nerve function tests were performed on the biopsied sites and erythrocyte aldose reductase level was determined by enzyme-linked immunosorbent assay. Numbers of epidermal NFs, NLs of epidermis and dermis and NL around sweat glands were significantly decreased in diabetic patients compared with control subjects (P<0.001, P<0.001, P<0.01, P<0.01, respectively). NL of epidermis showed a significant correlation with NL of dermis (P<0.01). Sural nerve conduction velocity was significantly correlated with NL of dermis (P10.8 (average in 555 diabetic patients) ng/mgHb) possessed a shorter NL of dermis NFs than those with lower AR level (<10.8) (P<0.05). These findings suggest that the quantitation of cutaneous nerves in biopsied skin samples provides important information about diabetic neuropathy and may improve the understanding of the pathophysiology of sensory nerve terminals in diabetic neuropathy.