Department of Clinical and Experimental Medicine Division of Cell Biology Linköping University Linköping Sweden.
Department of Hand Surgery Skåne University Hospital Malmö Sweden.
Brain Behav. 2017 Jul 12;7(8):e00763. doi: 10.1002/brb3.763. eCollection 2017 Aug.
The progression and pathophysiology of neuropathy in impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) is poorly understood, especially in relation to autophagy. This study was designed to assess whether the presence of autophagy-related structures was associated with sural nerve fiber pathology, and to investigate if endoneurial capillary pathology could predict the development of T2DM and neuropathy.
Sural nerve physiology and ultrastructural morphology were studied at baseline and 11 years later in subjects with normal glucose tolerance (NGT), IGT, and T2DM.
Subjects with T2DM had significantly lower sural nerve amplitude compared to subjects with NGT and IGT at baseline. Myelinated and unmyelinated fiber, endoneurial capillary morphology, and the presence and distribution of autophagy structures were comparable between groups at baseline, except for a smaller myelinated axon diameter in subjects with T2DM and IGT compared to NGT. The baseline values of the subjects with NGT and IGT who converted to T2DM 11 years later demonstrated healthy smaller endoneurial capillary and higher -ratio versus subjects who remained NGT. At follow-up, T2DM showed a reduction in nerve conduction, amplitude, myelinated fiber density, unmyelinated axon diameter, and autophagy structures in myelinated axons. Endothelial cell area and total diffusion barrier was increased versus baseline.
We conclude that small healthy endoneurial capillary may presage the development of T2DM and neuropathy. Autophagy occurs in human sural nerves and can be affected by T2DM. Further studies are warranted to understand the role of autophagy in diabetic neuropathy.
葡萄糖耐量受损（IGT）和 2 型糖尿病（T2DM）患者神经病变的进展和病理生理学尚不清楚，尤其是与自噬有关的方面。本研究旨在评估自噬相关结构的存在是否与腓肠神经纤维病理有关，并研究神经内膜毛细血管病理是否可以预测 T2DM 和神经病变的发生。
在正常糖耐量（NGT）、IGT 和 T2DM 受试者中，分别在基线时和 11 年后检测腓肠神经生理学和超微结构形态。
与 NGT 受试者相比，T2DM 受试者的腓肠神经振幅在基线时明显降低。各组的有髓纤维和无髓纤维、神经内膜毛细血管形态以及自噬结构的存在和分布在基线时是可比的，但与 NGT 相比，T2DM 和 IGT 受试者的有髓轴突直径较小。在 11 年后转变为 T2DM 的 NGT 和 IGT 受试者的基线值显示，与保持 NGT 的受试者相比，健康的神经内膜毛细血管较小，而比值较高。在随访时，T2DM 显示神经传导、振幅、有髓纤维密度、无髓轴突直径和有髓轴突中的自噬结构减少。内皮细胞面积和总扩散屏障较基线增加。
我们得出的结论是，较小的健康神经内膜毛细血管可能预示着 T2DM 和神经病变的发生。自噬发生在人类腓肠神经中，并可能受到 T2DM 的影响。需要进一步的研究来了解自噬在糖尿病神经病变中的作用。
