University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Diabetes Complications. 2021 Apr;35(4):107852. doi: 10.1016/j.jdiacomp.2021.107852. Epub 2021 Jan 9.
Recent studies suggest that the accumulation of atypical, 1-deoxysphingolipids that lack the C1 hydroxyl group may be associated with diabetic neuropathy (DN). We hypothesized that specific plasma 1-deoxysphingolipids associate with DN severity, and that alterations in plasma serine and alanine associate with 1-deoxysphingolipid elevation in patients with type 2 diabetes (T2D). We examined individual 1-deoxysphingolipid species using LC/MS/MS in plasma samples from 75 individuals including lean controls (LC, n = 19), those with obesity (n = 19), obesity with T2D without DN (ob/T2D, n = 18), and obesity with T2D with DN (Ob/T2D/DN, n = 19). We observed a step wise increase in 1-deoxydihydroceramides across these four groups (spearman correlation coefficient r = 0.41, p = 0.0002). Mean total concentrations of 1-deoxydihydroceramides, and most individual 1-deoxydihydroceramide species, were higher in ob/T2D/DN versus LC group (8.939 vs. 5.195 pmol/100 μL for total 1-deoxydihydroceramides p = 0.005). No significant differences in 1-deoxydihydroceramides were observed between the ob/T2D and ob/T2D/DN groups. l-alanine was higher and l-serine lower in ob/T2D/DN versus LC groups (326.2 vs. 248.0 μM, p = 0.0086 and 70.2 vs. 89.8 μM, p = 0.0110), consistent with a potential contribution of these changes to the observed 1-deoxysphingolipids profiles. 1-deoxydihydroceramides correlated inversely with leg intraepidermal nerve fiber density (CC -0.40, p = 0.003). These findings indicate that 1-deoxydihydroceramides may be important biomarkers and/or mediators of DN.
最近的研究表明，缺乏 C1 羟基的非典型 1-脱氧鞘氨醇的积累可能与糖尿病神经病变（DN）有关。我们假设特定的血浆 1-脱氧鞘氨醇与 DN 的严重程度有关，而在 2 型糖尿病（T2D）患者中，血浆丝氨酸和丙氨酸的变化与 1-脱氧鞘氨醇的升高有关。我们使用 LC/MS/MS 检查了来自 75 个人的血浆样本中的个体 1-脱氧鞘氨醇种类，包括瘦对照组（LC，n=19）、肥胖组（n=19）、肥胖合并无糖尿病神经病变的 T2D 组（ob/T2D，n=18）和肥胖合并糖尿病神经病变的 T2D 组（Ob/T2D/DN，n=19）。我们观察到这四个组的 1-脱氧二氢神经酰胺呈逐步增加（斯皮尔曼相关系数 r=0.41，p=0.0002）。ob/T2D/DN 组与 LC 组相比，总 1-脱氧二氢神经酰胺和大多数个体 1-脱氧二氢神经酰胺的平均浓度更高（总 1-脱氧二氢神经酰胺 8.939 与 5.195 pmol/100 µL，p=0.005）。ob/T2D 组和 ob/T2D/DN 组之间的 1-脱氧二氢神经酰胺无显著差异。ob/T2D/DN 组与 LC 组相比，丙氨酸升高，丝氨酸降低（326.2 与 248.0 µM，p=0.0086 和 70.2 与 89.8 µM，p=0.0110），这与这些变化对观察到的 1-脱氧鞘氨醇谱的潜在贡献一致。1-脱氧二氢神经酰胺与下肢表皮内神经纤维密度呈负相关（CC-0.40，p=0.003）。这些发现表明，1-脱氧二氢神经酰胺可能是糖尿病神经病变的重要生物标志物和/或介质。
