Kwai Natalie C G, Nigole William, Poynten Ann M, Brown Christopher, Krishnan Arun V
Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
Department of Endocrinology, Prince of Wales Hospital, Sydney, Australia.
PLoS One. 2016 Apr 14;11(4):e0153389. doi: 10.1371/journal.pone.0153389. eCollection 2016.
Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus. Treatment largely consists of symptom alleviation and there is a need to identify therapeutic targets for prevention and treatment of DPN. The objective of this study was to utilise novel neurophysiological techniques to investigate axonal function in patients with type 2 diabetes and to prospectively determine their relationship to serum lipids in type 2 diabetic patients.
Seventy-one patients with type 2 diabetes were consecutively recruited and tested. All patients underwent thorough clinical neurological assessments including nerve conduction studies, and median motor axonal excitability studies. Studies were also undertaken in age matched normal control subjects(n = 42). Biochemical studies, including serum lipid levels were obtained in all patients. Patient excitability data was compared to control data and linear regression analysis was performed to determine the relationship between serum triglycerides and low density lipoproteins and excitability parameters typically abnormal in type 2 diabetic patients.
Patient mean age was 64.2±2.3 years, mean glycosylated haemoglobin (HbA1c%) was 7.8±0.3%, mean triglyceride concentration was 1.6±0.1 mmol/L and mean cholesterol concentration was 4.1±0.2mmol/L. Compared to age matched controls, median motor axonal excitability studies indicated axonal dysfunction in type 2 diabetic patients as a whole (T2DM) and in a subgroup of the patients without DPN (T2DM-NN). These included reduced percentage threshold change during threshold electrotonus at 10-20ms depolarising currents (TEd10-20ms)(controls 68.4±0.8, T2DM63.9±0.8, T2DM-NN64.8±1.6%,P<0.05) and superexcitability during the recovery cycle (controls-22.5±0.9, T2DM-17.5±0.8, T2DM-NN-17.3±1.6%,P<0.05). Linear regression analysis revealed no associations between changes in axonal function and either serum triglyceride or low density lipoprotein concentration when adjusted for renal function, a separate risk factor for neuropathy development. Our findings indicate that acutely, serum lipids do not exert an acute effect on axonal function in type 2 diabetic patients: TEd(10-20ms)(1.2(-1.4,3.8);P = 0.4) and superexcitability (2.4(-0.05, 4.8);P = 0.06).
These findings suggest that serum triglyceride levels are not related to axonal function in type 2 diabetic patients. Additional pathogenic mechanisms may play a more substantial role in axonal dysfunction prior to DPN development.
糖尿病周围神经病变（DPN）是糖尿病常见且使人衰弱的并发症。治疗主要包括缓解症状，因此需要确定预防和治疗DPN的治疗靶点。本研究的目的是利用新型神经生理学技术研究2型糖尿病患者的轴突功能，并前瞻性地确定其与2型糖尿病患者血脂的关系。
连续招募并测试了71例2型糖尿病患者。所有患者均接受了全面的临床神经学评估，包括神经传导研究和正中运动轴突兴奋性研究。还对年龄匹配的正常对照受试者（n = 42）进行了研究。所有患者均进行了生化研究，包括血脂水平检测。将患者的兴奋性数据与对照数据进行比较，并进行线性回归分析，以确定血清甘油三酯和低密度脂蛋白与2型糖尿病患者中通常异常的兴奋性参数之间的关系。
患者的平均年龄为64.2±2.3岁，平均糖化血红蛋白（HbA1c%）为7.8±0.3%，平均甘油三酯浓度为1.6±0.1 mmol/L，平均胆固醇浓度为4.1±0.2mmol/L。与年龄匹配的对照组相比，正中运动轴突兴奋性研究表明，2型糖尿病患者总体（T2DM）以及无DPN的患者亚组（T2DM-NN）存在轴突功能障碍。这些指标包括在10 - 20ms去极化电流的阈下电紧张期间阈值变化百分比降低（TEd10 - 20ms）（对照组68.4±0.8，T2DM 63.9±0.8，T2DM-NN 64.8±1.6%，P<0.05）以及恢复周期中的超兴奋性（对照组-22.5±0.9，T2DM - 17.5±0.8，T2DM-NN - 17.3±1.6%，P<0.05）。线性回归分析显示，在调整了肾功能（神经病变发展的另一个危险因素）后，轴突功能变化与血清甘油三酯或低密度脂蛋白浓度之间无关联。我们的研究结果表明，急性情况下，血脂对2型糖尿病患者的轴突功能无急性影响：TEd(10 - 20ms)(1.2(-1.4,3.8);P = 0.4)和超兴奋性(2.4(-0.05, 4.8);P = 0.06)。
这些发现表明，2型糖尿病患者的血清甘油三酯水平与轴突功能无关。在DPN发生之前，其他致病机制可能在轴突功能障碍中起更重要的作用。
