Sima A A, Nathaniel V, Bril V, McEwen T A, Greene D A
Department of Pathology, University of Manitoba, Winnipeg, Canada.
J Clin Invest. 1988 Feb;81(2):349-64. doi: 10.1172/JCI113327.
Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.
山梨醇和肌醇代谢改变、（钠，钾）-ATP酶功能、电化学钠梯度、轴突肿胀以及郎飞结的扭曲和破坏（“轴突-神经胶质分离”）直接表明高血糖在糖尿病大鼠神经病变发病机制中起作用，但这一序列与糖尿病患者异质性群体临床神经病变的相关性仍有待确定。与年龄匹配的对照组相比，11例患有胰岛素依赖型糖尿病并发神经病变患者的束状腓肠神经形态测量显示出一种相互关联的结构变化模式，与糖尿病大鼠的模式惊人地相似。17例年龄较大的非胰岛素依赖型糖尿病患者，其高血糖持续时间和严重程度以及神经病变严重程度相当，与年龄匹配的对照组相比，显示出相似的神经纤维丧失、结旁脱髓鞘、结旁再髓鞘化和节段性脱髓鞘，但轴突-神经胶质分离被华勒变性所取代，成为纤维损伤的主要表现，并且纤维丧失以与缺血成分一致的空间模式发生。从糖尿病大鼠建立的机制模型确实似乎适用于人类糖尿病神经病变，但叠加的激素、代谢、血管和/或年龄相关效应会改变非胰岛素依赖型糖尿病中神经病变的形态学表现。
