Hur Junguk, Sullivan Kelli A, Callaghan Brian C, Pop-Busui Rodica, Feldman Eva L
Corresponding author: Eva L. Feldman,
Diabetes Care. 2013 Dec;36(12):4043-9. doi: 10.2337/dc12-2530. Epub 2013 Oct 7.
Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN.
Demographic, anthropometric, biochemical, and anatomical data of subjects with DN from a 52-week trial of acetyl-L-carnitine were retrospectively examined. Based on the change in sural nerve myelinated fiber density (ΔMFD%), subjects were divided into three groups: regenerator (top 16 percentiles, n = 67), degenerator (bottom 16 percentiles, n = 67), and intermediate (n = 290), with dramatically increased, decreased, and steady ΔMFD%, respectively. ANOVA, Fisher exact test, and multifactorial logistic regression were used to evaluate statistical significance.
ΔMFD%s were 35.6 ± 17.4 (regenerator), -4.8 ± 12.1 (intermediate), and -39.8 ± 11.0 (degenerator). HbA1c at baseline was the only factor significantly different across the three groups (P = 0.01). In multifactorial logistic regression, HbA1c at baseline was also the only risk factor significantly different between regenerator (8.3 ± 1.6%) and degenerator (9.2 ± 1.8%) (odds ratio 0.68 [95% CI 0.54-0.85]; P < 0.01). Support Vector Machine classifier using HbA1c demonstrated 62.4% accuracy of classifying subjects into regenerator or degenerator. A preliminary microarray experiment revealed that upregulated genes in the regenerator group are enriched with cell cycle and myelin sheath functions, while downregulated genes are enriched in immune/inflammatory responses.
These data, based on the largest cohort with ΔMFD% information, suggest that HbA1c levels predict myelinated nerve fiber regeneration and degeneration in patients with DN. Therefore, maintaining optimal blood glucose control is likely essential in patients with DN to prevent continued nerve injury.
糖尿病神经病变（DN）患者表现出不同程度的神经再生和退变。我们的目的是确定与DN患者腓肠神经退变相关的危险因素。
回顾性分析了一项为期52周的乙酰-L-肉碱试验中DN受试者的人口统计学、人体测量学、生化和解剖学数据。根据腓肠神经有髓纤维密度的变化（ΔMFD%），将受试者分为三组：再生组（前16百分位数，n = 67）、退变组（后16百分位数，n = 67）和中间组（n = 290），其ΔMFD%分别显著增加、降低和稳定。采用方差分析、Fisher精确检验和多因素逻辑回归来评估统计学意义。
再生组、中间组和退变组的ΔMFD%分别为35.6±17.4、-4.8±12.1和-39.8±11.0。基线时的糖化血红蛋白是三组间唯一有显著差异的因素（P = 0.01）。在多因素逻辑回归中，基线时的糖化血红蛋白也是再生组（8.3±1.6%）和退变组（9.2±1.8%）之间唯一有显著差异的危险因素（比值比0.68 [95% CI 0.54 - 0.85]；P < 0.01）。使用糖化血红蛋白的支持向量机分类器将受试者分为再生组或退变组的准确率为62.4%。一项初步的微阵列实验显示，再生组中上调的基因富含细胞周期和髓鞘功能，而下调的基因则富含免疫/炎症反应。
这些基于拥有ΔMFD%信息的最大队列的数据表明，糖化血红蛋白水平可预测DN患者有髓神经纤维的再生和退变。因此，对DN患者而言，维持最佳血糖控制可能对预防持续神经损伤至关重要。
