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Pathogenesis and prevention of diabetic polyneuropathy

Eva L Feldman, MD, PhD
Section Editor
Jeremy M Shefner, MD, PhD
Deputy Editor
John F Dashe, MD, PhD


Involvement of the peripheral and autonomic nervous systems is probably the most common complication of diabetes. The duration and severity of hyperglycemia is an important risk factor for the development of diabetic neuropathy in patients with type 1 or type 2 diabetes.

This topic will address the pathogenesis and prevention of diabetic polyneuropathy. Other issues related to diabetic neuropathy are discussed separately. (See "Epidemiology and classification of diabetic neuropathy" and "Clinical manifestations and diagnosis of diabetic polyneuropathy" and "Treatment of diabetic neuropathy".)


Distal symmetric polyneuropathy is the most common form of diabetic neuropathy [1,2]. The proximate cause is a length-dependent "dying back" axonopathy, primarily involving the distal portions of the longest myelinated and unmyelinated sensory axons, with relative sparing of motor axons [3-5]. Though distal "dying back" is commonly seen, there is also evidence for proximal nerve dysfunction at the sensory ganglia, which may contribute to this phenomenon [6]. In addition, the spinal cord appears to be affected; it is not clear if this is a primary neuropathic involvement of the cord or is due to the diabetes itself [7,8].

Distal symmetric polyneuropathy is morphologically and functionally indistinguishable from many other "metabolic" neuropathies, including uremic neuropathy and alcoholic neuropathy. However, in diabetic polyneuropathy, morphologic abnormalities of the vaso nervorum are present early in the course of the disease [9], and parallel the severity of the nerve fiber loss [10-12]. Thus, the morphologic characteristics of diabetic polyneuropathy are consistent with either a vascular or a metabolic etiology [13].


The duration and severity of hyperglycemia are major risk factors for the development of diabetic neuropathy in patients with type 1 or type 2 diabetes [14,15]. Other investigations have extended the known risk factors to include glycemic variability, age, dyslipidemia, hypertension, and smoking [16-20].

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Literature review current through: Dec 2017. | This topic last updated: Jul 06, 2017.
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