COMPLICATIONS - NEUROPATHY, PATHOGENETIC CONSIDERATIONS
COMPLICATIONS - NEUROPATHY, PATHOGENETIC CONSIDERATIONS
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DOI：
10.2337/diacare.15.12.1902
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发表时间：
1992-12-01
期刊：
影响因子：
16.2
通讯作者：
LATTIMER, SA
中科院分区：
文献类型：
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作者：
GREENE, DA;SIMA, AAF;LATTIMER, SA
与糖尿病相关的最常见的神经病变形式是远端对称性感觉运动多发性神经病变，通常伴有自主神经病变。这种疾病的特征在于显著的萎缩和有髓和无髓纤维的损失，伴随着沃勒变性、节段性和结旁脱髓鞘以及钝化的神经纤维再生。在人类和实验动物中，这种进行性神经纤维损伤和损失与高血糖症的程度和/或持续时间平行。已经提出了几种代谢机制来解释高血糖的程度和严重程度与糖尿病神经病变的发展之间的关系。其中一种机制是葡萄糖通过AR激活多元醇途径，这是糖尿病大鼠外周神经的一个显著代谢特征，它通过改变神经Na+-K+-ATP酶活性或干扰正常生理性神经递质调节机制，促进山梨糖醇和果糖积累、肌醇消耗和神经传导减慢。阿里斯，使神经肌醇和神经传导减慢正常化，是目前临床试验的重点。其他可能在糖尿病神经病变发病机制中起作用的特定代谢异常包括脂质或氨基酸代谢异常、超氧化物自由基形成、蛋白质糖化或正常神经营养反应的潜在钝化。糖尿病神经的代谢功能障碍伴随着血管功能不全和神经缺氧，可能导致神经纤维损失和损伤。虽然关于糖尿病神经病变的发病机制的主要问题仍然没有答案，需要进一步深入研究，但最近的重大进展正在推动我们走向未来，并且可能仅构成针对负责糖尿病神经病变的复杂发病过程的一个或多个要素的许多疗法中的第一个。
The most common form of neuropathy associated with diabetes mellitus is distal symmetric sensorimotor polyneuropathy, often accompanied by autonomic neuropathy. This disorder is characterized by striking atrophy and loss of myelinated and unmyelinated fibers accompanied by Wallerian degeneration, segmental, and paranodal demyelination and blunted nerve fiber regeneration. In both humans and laboratory animals, this progressive nerve fiber damage and loss parallels the degree and/or duration of hyperglycemia. Several metabolic mechanisms have been proposed to explain the relationship between the extent and severity of hyperglycemia and the development of diabetic neuropathy. One mechanism, activation of the polyol pathway by glucose via AR, is a prominent metabolic feature of diabetic rat peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-inositol depletion, and slowing of nerve conduction by alteration of neural Na+-K+-ATPase activity or perturbation of normal physiological osmoregulatory mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction slowing, are currently the focus of clinical trials. Other specific metabolic abnormalities that may play a role in the pathogenesis of diabetic neuropathy include abnormal lipid or amino acid metabolism, superoxide radical formation, protein glycation, or potential blunting of normal neurotrophic responses. Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency and nerve hypoxia that may contribute to nerve fiber loss and damage. Although major questions about the pathogenesis of diabetic neuropathy remain unanswered and require further intense investigation, significant recent progress is pushing us into the future and likely constitutes only the first of many therapies directed against one or more elements of the complex pathogenetic process responsible for diabetic neuropathy.