Evaluation Of Diabetic Neuropathy By Skin Biopsy

Abstract

Instead of nerve biopsy which is most reliable method for diagnosing diabetic neuropathy but rather harmful, we have examined the usefulness of skin biopsy to evaluate the grade of diabetic neuropathy and therapeutic effects of given compounds. Nerve fibers immunostained by antibodies against protein gene product (PGP)9.5 and labeled with streptavidin fluorescein isothiocyanate and measured under confocal laser scanning microscopy were significantly shorter in the epidermis and dermis and around sweat glands in diabetic patients than in healthy subjects. Sural nerve conduction velocity was significantly correlated with dermal nerve fiber length (NFL) (p < 0.05) in diabetic patients. Patients with higher aldose reductase (AR) level of erythrocytes (>10.8 ng/Hg) showed shorter dermal NFL than those with lower AR level (<10.8)(p < 0.05). Using this technique, we evaluated the therapeutic effect of AR inhibitor (ARI) epalrestat during approximately 13 months in diabetic patients with neuropathy (19, epalrestat‐treated; 12, control). The number of patients whose percent change of dermal NFL exceeded its mean ± 2SD in the control group was significantly higher in the ARI group than in the control group (p < 0.05, 8/9 vs 1/12). These results suggest that quantitation of cutaneous nerves using biopsied skin samples may provide important information about the severity of diabetic neuropathy and that epalrestat can elongate dermal unmyelinated nerve fibers in at least part of diabetic patients.