This patient has numbness and paresthesias in a stocking-glove distribution, along with decreased proprioception (eg, decreased joint position sense) consistent with diabetic polyneuropathy.  Diabetes mellitus is the most common cause of peripheral neuropathy in adults.  The risk of neuropathy and other microvascular complications (eg, retinopathy, nephropathy) is increased in longstanding, poorly controlled diabetes; tight glycemic control can decrease the risk.

Neuronal injury occurs due to accumulation of advanced glycosylation end products, sorbitol, and other toxic substances that lead to deranged metabolism and increased oxidative stress.  In addition, diabetic microangiopathy affecting the endoneurial vessels can promote nerve ischemia.  This, in combination with the metabolic disturbances, leads to a length-dependent axonopathy, with clinical features occurring first in the longest nerves (eg, feet); symptoms vary depending on the type of nerve fibers involved:

• Small-fiber injury is characterized by predominance of positive symptoms (eg, pain, paresthesias, allodynia).

• Large-fiber involvement is characterized by predominance of negative symptoms (eg, numbness, loss of proprioception and vibration sense, sensory ataxia [eg, positive Romberg sign], diminished ankle reflexes).

Patients with diabetes can also develop autonomic neuropathy, manifesting as gastrointestinal disturbances (eg, gastroparesis), orthostatic symptoms, bladder dysfunction, and erectile dysfunction.  Degeneration of motor axons may also occur, leading to unbalanced strength in the extremities and hammer or claw toe deformities.

(Choice A)  C-fibers are small, unmyelinated fibers that carry pain and temperature sensation.  Diabetes can damage these fibers, leading to a reduction in pain/temperature sensation as well as burning pain.  Numbness, tingling paresthesias, diminished reflexes, and sensory ataxia are more consistent with large-fiber neuropathy.

(Choice C)  Nerve root dysfunction (ie, radiculopathy) is most commonly due to compression from disc herniation or degenerative changes in the vertebral column.  The associated pain/numbness is in a dermatomal (rather than stocking-glove) distribution and is often associated with muscular weakness and atrophy.

(Choice D)  Guillain-Barré syndrome is an immune-mediated polyneuropathy caused by demyelination of peripheral nerve fibers.  It can cause paresthesias and neuropathic pain but typically presents with rapidly progressive ascending weakness.  Most patients have a preceding respiratory or gastrointestinal infection (eg, Campylobacter).

(Choice E)  Subacute combined degeneration of the spinal cord results from chronic vitamin B₁₂ deficiency.  Manifestations in the posterior columns can include loss of proprioception, paresthesia, and sensory ataxia, but concurrent lateral corticospinal tract signs (eg, spastic paresis) and other signs of B₁₂ deficiency (eg, atrophic glossitis, macrocytic anemia) are typically present.

Educational objective:
Diabetes mellitus is the most common cause of peripheral polyneuropathy in adults.  Common findings include numbness and paresthesias in a stocking-glove distribution and decreased proprioception due to degeneration of large-fiber sensory axons.