Monograph: Diabetic Neuropathies-Article

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This 2025 AANEM monograph comprehensively reviews diabetic neuropathies (DPN), common complications of diabetes affecting over half a billion people worldwide. DPN manifests in varied forms including distal symmetric polyneuropathy (most common), radiculoplexus neuropathies, mononeuropathies, autonomic neuropathy, and cachectic neuropathy, presenting with motor deficits, sensory abnormalities, neuropathic pain (NP), and autonomic dysfunction.<br /><br />Epidemiologically, DPN affects over 50% lifetime in diabetes, with higher prevalence in type 2 diabetes (20-30%) compared to type 1. Risk factors include duration of diabetes, glycemic control, age, metabolic syndrome, and cardiovascular risks. Pathophysiologically, sensory neurons in the peripheral nervous system are vulnerable due to their exposure outside the blood-brain barrier and long axons leading to mitochondrial bioenergetic failure from hyperglycemia and dyslipidemia.<br /><br />Clinically, large fiber neuropathy manifests with numbness, proprioceptive loss, and distal muscle weakness, while small fiber neuropathy mainly causes painful symptoms and autonomic dysfunction affecting cardiac, gastrointestinal, and genitourinary systems. Some patients may be asymptomatic despite nerve damage, increasing risk for fall, ulcers, and amputations. Specific types like diabetic radiculoplexus neuropathies are less common but cause severe asymmetric proximal weakness and pain.<br /><br />Evaluation involves clinical history and exam focusing on sensory testing, reflexes, gait, and autonomic symptoms. Common neuropathy scales assist in staging severity; electrodiagnostic studies help diagnose large fiber involvement, while skin biopsy may assess small fibers. Autonomic testing is reserved for disabling symptoms.<br /><br />There is no disease-modifying treatment; prevention centers on maintaining optimal and stable glycemic control. Management of painful DPN includes FDA-approved pregabalin and duloxetine, with other anticonvulsants and tricyclic antidepressants as common pharmacologic options. Opioids and cannabis-based medicines have insufficient or unfavorable evidence. Nutraceuticals like α-lipoic acid and benfotiamine may be adjuncts but lack robust data for first-line use.<br /><br />Nonpharmacologic therapies emphasize lifestyle modifications such as exercise, diet, and behavioral interventions. Nerve stimulation techniques such as TENS and spinal cord stimulation may be considered for refractory pain but lack evidence to alter disease progression. Overall, more research is needed on prevention, assessment, and therapeutic strategies to reduce DPN morbidity and healthcare costs.
Keywords
diabetic neuropathies
DPN
distal symmetric polyneuropathy
radiculoplexus neuropathies
neuropathic pain
glycemic control
large fiber neuropathy
small fiber neuropathy
pregabalin
α-lipoic acid