To detect small fiber neuropathy in patients with possible or established diabetic peripheral neuropathy (DPN) by skin punch biopsy and explore clinical characteristics and pathological features in different DPN patients.

A total of 37 patients were collected with possible or established DPN from December 2015 to February 2018. All patients underwent skin punch biopsy, intra epidermal nerve fiber density (IENFD) calculation, nerve conduction studies and clinical examination of neurological signs and symptoms. Fifteen healthy subjects were set as control. Chi-square test was used to analyze the impact of biopsy on DPN diagnosis rate. Student t test and Wilcoxon rank sum test were utilized to compare the difference of clinical characteristic and pathological feature between two subtypes of DPN patients.

The average IENFD in control was (13.4±0.8) fiber/mm in calf and (21.1±5.9) fiber/mm in thigh while the diagnostic cutoff point of DPN was 13.0 fiber/mm in calf and 11.4 fiber/mm in thigh, respectively. Among total 37 patients, 35 were diagnosed as small fiber neuropathy by using skin punch biopsy and the proportion of DPN raised from 73% (27/37) to 95% (35/37) (P<0.05), which included 8 patients with primarily small fiber neuropathy and 27 patients with mixed small and large fiber neuropathy. Patients with primarily small fiber neuropathy had lower level of glycated hemoglobin A_1c, lower proportion of diabetic retinopathy, nephropathy and cardiovascular autonomic neuropathy and higher IENFD in thigh [(8.8±2.6) vs (4.5±1.8) fiber/mm, t=5.424, P<0.01] than patients with mixed small and large fiber neuropathy. IENFD in calf was not significantly different between groups [(1.5±1.2) vs (2.5±1.3) fiber/mm, t=-1.965, P>0.05].

Skin punch biopsy can significantly improve DPN diagnosis rate and is an important tool for identifying diabetic small fiber neuropathy.

Diabetic neuropathies; Skin punch biopsy; Intra epidermal nerve fiber density; Small fiber neuropathy