Smith A Gordon, Russell James, Feldman Eva L, Goldstein Jonathan, Peltier Amanda, Smith Sheldon, Hamwi Jouhaina, Pollari Donald, Bixby Billie, Howard James, Singleton J Robinson
Department of Neurology, University of Utah School of Medicine, 50 N. Medical Drive, SOM 3R152, Salt Lake City, UT 84132, USA.
Diabetes Care. 2006 Jun;29(6):1294-9. doi: 10.2337/dc06-0224.
The purpose of this study was to evaluate intraepidermal nerve fiber density (IENFD) as a sensitive measure of neuropathy change in patients with neuropathy associated with impaired glucose tolerance (IGT) receiving lifestyle intervention based on that used in the Diabetes Prevention Program.
We performed 3-mm skin biopsies with measurement of IENFD at the distal leg and proximal thigh at baseline and after 1 year in 32 subjects with IGT. Each received individualized diet and exercise counseling as a standard of care. Nerve conduction studies, quantitative sensory testing, quantitative sudomotor axon reflex testing, and the Michigan Diabetic Neuropathy score were performed, and a visual analog pain scale was completed. Two-hour oral glucose tolerance tests (OGTTs) following the American Diabetes Association guidelines were performed, and serum lipid levels were measured at baseline and 1 year later.
Baseline distal IENFD was 0.9 +/- 1.2 fibers/mm and proximal IENFD was 4.8 +/- 2.3 fibers/mm. Baseline distal IENFD correlated with fasting glucose (P < 0.001) and OGTT (P < 0.01). After 1 year of treatment, there was a 0.3 +/- 1.1-fiber/mm improvement in distal IENFD and a 1.4 +/- 2.3-fiber/mm improvement in proximal IENFD (P < 0.004). The change in proximal IENFD correlated with decreased neuropathic pain (P < 0.05) and a change in sural sensory amplitude (P < 0.03).
These findings indicate that diet and exercise counseling for IGT results in cutaneous reinnervation and improved pain. Skin biopsy was the most sensitive measure of neuropathy change over 1 year. IENFD should be included as an end point in future neuropathy trials.
本研究旨在评估表皮内神经纤维密度（IENFD），以此作为糖耐量受损（IGT）相关神经病变患者接受基于糖尿病预防计划的生活方式干预后神经病变变化的敏感指标。
我们对32例IGT患者在基线和1年后进行了3毫米皮肤活检，测量小腿远端和大腿近端的IENFD。每位患者均接受个体化饮食和运动咨询作为标准治疗。进行了神经传导研究、定量感觉测试、定量汗腺轴突反射测试以及密歇根糖尿病神经病变评分，并完成了视觉模拟疼痛量表。按照美国糖尿病协会指南进行了两小时口服葡萄糖耐量试验（OGTT），并在基线和1年后测量血清脂质水平。
基线时小腿远端IENFD为0.9±1.2根纤维/毫米，大腿近端IENFD为4.8±2.3根纤维/毫米。基线时小腿远端IENFD与空腹血糖（P<0.001）和OGTT（P<0.01）相关。治疗1年后，小腿远端IENFD改善了0.3±1.1根纤维/毫米，大腿近端IENFD改善了1.4±2.3根纤维/毫米（P<0.004）。大腿近端IENFD的变化与神经性疼痛减轻（P<0.05）和腓肠感觉振幅变化（P<0.03）相关。
这些发现表明，对IGT患者进行饮食和运动咨询可导致皮肤神经再支配并减轻疼痛程度。皮肤活检是1年内神经病变变化最敏感的指标。IENFD应作为未来神经病变试验的一个终点指标。
