Pek Sharon Li Ting, Sum Chee Fang, Yeoh Lee Ying, Lee Simon Biing Ming, Tang Wern Ee, Lim Su Chi, Tavintharan Subramaniam
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore 768828.
Diabetes Centre, Khoo Teck Puat Hospital, Singapore 768828; Division of Endocrinology, Department of Medicine, Khoo Teck Puat Hospital, Singapore 768828.
Metabolism. 2017 Jul;72:75-82. doi: 10.1016/j.metabol.2017.03.016. Epub 2017 Apr 2.
Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes (T2D). Apart from hyperglycemia, its pathogenesis is poorly understood. Apolipoprotein-CIII (apoC-III) associated with triglyceride metabolism, is a risk factor for cardiovascular disease. Its role in DPN is not well-established. We studied the associations of apoC-III, endothelial function and DPN.
In patients with T2D, anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements (uACR). Endothelial function assessments were performed by laser Doppler flowmetry/imaging. DPN was considered present if there was an abnormal finding in monofilament (≤8 of 10 points) or neurothesiometer testing≥25V on either foot. Plasma apoC-III was assessed by ELISA.
Monofilament and neurothesiometer readings were measured in 1981 patients, mean age 57.4±10.8 years old. DPN prevalence was 10.8% (n=214). Patients with DPN compared to those without, were significantly older (p<0.0001), with longer duration of T2D (p<0.0001), had higher BMI (p=0.006), higher glucose (p=0.015) and HbA1c (p<0.0001), Systolic blood pressure (SBP) (p<0.0001), lower eGFR (p<0.0001), higher urine ACR (p<0.0001), poorer endothelium-dependent and endothelium-independent vasodilation (both p<0.0001), higher VCAM-1 (p<0.0001) and higher apoC-III [285.3 (195.2-405.6) vs 242.9(165.0-344.0) μg/ml]. After adjustment, log transformed apoC-III, remained independently associated with the presence of DPN (B=0.965, SE=0.397, p=0.015).
Plasma apoC-III is higher in patients with DPN. Apart from its known association with lipids and macrovascular complications, this study suggests its association with DPN. Whether regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidemia and microvascular complications in T2D remains to be proven in future mechanistic and clinical studies.
糖尿病周围神经病变（DPN）是2型糖尿病（T2D）的常见并发症。除高血糖外，其发病机制尚不清楚。载脂蛋白C-III（apoC-III）与甘油三酯代谢相关，是心血管疾病的危险因素。其在DPN中的作用尚未明确。我们研究了apoC-III、内皮功能与DPN之间的关联。
收集T2D患者的人体测量数据、空腹血液和尿液，进行生化检查及尿白蛋白/肌酐比值（uACR）测量。采用激光多普勒血流仪/成像技术评估内皮功能。若单丝试验（10分制中≤8分）或双脚神经感觉阈值测量≥25V出现异常，则判定存在DPN。采用酶联免疫吸附测定法（ELISA）评估血浆apoC-III。
对1981例患者进行了单丝试验和神经感觉阈值测量，平均年龄57.4±10.8岁。DPN患病率为10.8%（n = 214）。与未患DPN的患者相比，患DPN的患者年龄显著更大（p<0.0001），T2D病程更长（p<0.0001），体重指数（BMI）更高（p = 0.006），血糖、糖化血红蛋白（HbA1c）更高（p分别为0.015、<0.0001），收缩压（SBP）更高（p<0.0001），估算肾小球滤过率（eGFR）更低（p<0.0001），尿ACR更高（p<0.0001），内皮依赖性和非内皮依赖性血管舒张功能更差（p均<0.0001），血管细胞黏附分子-1（VCAM-1）更高（p<0.0001），apoC-III更高[285.3（195.2 - 405.6）vs 242.9（165.0 - 344.0）μg/ml]。调整后，对数转换后的apoC-III仍与DPN的存在独立相关（B = 0.965，标准误 = 0.397，p = 0.015）。
DPN患者的血浆apoC-III更高。除了其与脂质及大血管并发症的已知关联外，本研究提示其与DPN有关联。调节apoC-III代谢是否可能成为管理T2D血脂异常和微血管并发症的一种重要新治疗方法，仍有待未来的机制研究和临床研究加以证实。
