Table 1.

Clinical presentation and management of the diabetic neuropathies.

	Uremic neuropathy (UN)	Diabetic peripheral neuropathy (DPN)	Cardiac autonomic neuropathy (CAN)
Affected nerves	Distal symmetric polyneuropathy of sensory, motor and autonomic nerves including renal sympathetic nerves	Distal symmetric polyneuropathy of sensory and motor nerves. Distal sympathetic autonomic neuropathy may also be observed	Parasympathetic and sympathetic autonomic nerves of the heart and the vasculature
	In rare cases: cranial and pulmonary sympathetic nerves
Pathogenesis	Exact mechanism unclear	Exact mechanism unclear	Exact mechanism unclear
	Advanced renal disease and build-up of uremic toxins are thought to affect neuron function	Hyperglycemia is thought to affect numerous pathways, causing nerve damage and inhibiting repair mechanisms	Hyperglycemia is thought to lead to accumulation of AGE products, which signal through their receptor RAGE, inducing chronic inflammation and nerve damage
Symptoms	Early sensory symptoms	Early sensory symptoms	Subclinical stage
	• Paresthesia	• Neuropathic pain	• Parasympathetic and sympathetic tone imbalance
	• Paradoxical heat sensation	• Sensitivity changes to vibration and temperature	• HRV changes
	• Increased pain sensation in lower extremities	• Numbness	• Alterations in baroreflex sensitivity
	• Restless leg syndrome		• Abnormalities in left ventricle
	• Cramps	Advanced disease motor-deficit symptoms
		• Muscle weakness	Clinical stage
	Advanced disease motor-deficit symptoms	• Foot deformities	• Resting tachycardia
	• Muscle weakness	• Impaired deep tendon reflexes	• Exercise intolerance
	• Impaired deep tendon reflexes	• Imbalance	• Postural hypotension
	• Imbalance	• Changes in gait and postural sway	• Cardiac dysfunction
	• Numbness	Distal sympathetic autonomic neuropathy	• Diabetic cardiomyopathy
	• Atrophy of lower limbs	• Dry, cracked and warm skin
	Autonomic impairment	• Plantar calluses at weight-bearing areas
	• Postural hypotension
	• Hyperhidrosis
	• Dysfunction of digestive, excretory and reproductive organs
Diagnosis of somatic neuropathy	• Neurological assessment	• Physical examination of feet
	• Nerve conduction velocity testing	• Perception of vibration, temperature, pain
		• Ankle reflex
Diagnosis of autonomic neuropathy	• Foot muscle strength
	• HRV	• Cardiovascular autonomic reflex tests	• Cardiovascular autonomic reflex tests
		• HRV	• HRV
Treatment	No preventative treatment	No preventative treatment	No preventative treatment
	Dialysis and renal transplantation	Intensive control of glycemia, lipidemia, hypertension and lifestyle changes reduce risk	Intensive control of glycemia, lipidemia, hypertension and lifestyle changes reduce risk