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Handbook of Diabetes, 4th Ed., Excerpt #16: Diabetic Neuropathy

Nov 2, 2014

Rudy Bilous, MD, FRCP
Richard Donnelly, MD, PHD, FRCP, FRACP


Symptoms, signs and classification


Diabetes is one of the most common causes of peripheral neuropathy, a term that encompasses a heterogeneous group of disorders (Figure 17.1). In population-based surveys, up to one-third of patients with diabetes have evidence of peripheral neuropathy but many are asymptomatic. Diabetic neuropathy should not be diagnosed solely on the basis of one symptom, physical sign or test; it is recommended that a minimum of two abnormalities be detected (symptoms, signs or test abnormalities – nerve conduction, quantitative sensory testing or quantitative autonomic testing) (Box 17.1)….

Healthy nerves consist of myelinated and unmyelinated nerve fibers or axons. The pathophysiology of diabetic neuropathy is complex, but microvascular disease affecting small vessels (the vasa vasorum) that supply oxygen and nutrients to peripheral nerves results in ischemic and metabolic neuronal injury via activation of several biochemical pathways, in particular the polyol pathway, non-enzymatic glycation and formation of advanced glycation endproducts (AGEs), activation of diacylglycerol-protein kinase C-ß , transcription factors (e.g. NFκB) and mitogen-activated protein kinase (MAPK), and the accumulation of reactive oxygen species (ROS) (Figure 17.2).

Chronic sensorimotor neuropathy

Chronic sensorimotor neuropathy is the most common form of diabetic neuropathy. This results from the distal dying back of axons that begins in the longest nerves; thus, the feet are affected first in a stocking distribution, and later there may be progressive involvement of the upper limbs. Sensory loss is most evident; autonomic involvement is usual, although it is mostly symptomless. Positive painful symptoms tend to be worse at night. Neurological examination shows a symmetrical sensory loss to all modalities, reduced or absent ankle or knee reflexes, and small muscle wasting of the feet and hands (Figure 17.3). The foot at high risk of neuropathic ulceration might have a high arch (pes cavus deformity) and clawing of the toes.

A simple staging system has been developed for diabetic neuropathy (Box 17.2).