What is peripheral neuropathy, particularly in older adults with a history of diabetes?

What is Peripheral Neuropathy?

Peripheral neuropathy is damage to the peripheral nerves that causes sensory, motor, and autonomic dysfunction, most commonly presenting as a symmetric, length-dependent process affecting the feet first with symptoms of numbness, tingling, burning pain, or loss of protective sensation. 1

Definition and Epidemiology

Peripheral neuropathy affects approximately 1% of adults worldwide, increasing to 7% in those over 65 years of age. 1, 2 In older adults with diabetes, the prevalence is substantially higher—10-15% of newly diagnosed type 2 diabetes patients have diabetic peripheral neuropathy (DPN), and this increases to over 50% in those with diabetes duration exceeding 10 years. 3

Diabetic neuropathy is the most common cause of peripheral neuropathy in Western populations, accounting for more than 50% of cases. 1 This is particularly relevant for older adults with diabetes, where neuropathy represents a heterogeneous group of disorders with diverse clinical manifestations. 4

Clinical Presentation

Sensory Symptoms (Small Fiber Involvement)

The earliest and most common symptoms result from small nerve fiber damage and include: 4, 5

• Burning pain described as constant or intermittent
• "Electrical shock" sensations or stabbing, knife-like pains
• Dysesthesias (unpleasant tingling sensations)
• Altered temperature perception—feet feeling abnormally hot or cold, or experiencing heat sensation after cold exposure
• Allodynia—pain from normally non-painful stimuli like clothing touching the skin 5
• Pain characteristically worse at night, often causing sleep disturbance 5

Patients may describe discomfort as "walking barefoot on marbles" or "walking barefoot on hot sand." 5

Large Fiber Involvement

As neuropathy progresses to involve large myelinated fibers, patients develop: 4, 6

• Numbness and loss of protective sensation (LOPS)
• Loss of proprioception leading to balance problems
• Decreased or absent reflexes in the lower extremities
• Ataxia with difficulty walking and positive Romberg sign 6
• Vibration sense loss

Critical Clinical Feature: Asymptomatic Neuropathy

Up to 50% of diabetic peripheral neuropathy may be completely asymptomatic. 4, 6 This is a dangerous situation because without recognition and preventive foot care, these patients are at high risk for injuries, diabetic foot ulcers, and amputations. 4 The absence of symptoms does not exclude significant nerve damage. 4

Pattern of Involvement

Peripheral neuropathy is typically: 1

• Length-dependent—symptoms begin in the toes and progress proximally over time in a "stocking and glove" distribution
• Symmetric—affecting both sides equally (asymmetric symptoms should prompt investigation for other causes) 5
• Predominantly sensory—affecting sensory axons more than motor axons initially

Pathophysiology in Diabetic Patients

In diabetes, the pathogenesis involves multiple interconnected mechanisms: 3

• Hyperglycemia-induced oxidative stress damaging nerve axons
• Microvascular damage impairing nerve blood supply
• Abnormal insulin signaling inhibiting neural repair and promoting apoptosis
• Metabolic derangements including lipid metabolism disorders
• Neuroinflammation and mitochondrial dysfunction

These processes disrupt the normal structure and function of myelinated and unmyelinated nerve axons, perikaryon, neurovascular structures, and glial cells. 3

Clinical Consequences and Complications

Foot Ulceration Risk

Peripheral sensory neuropathy is the single most common component cause for foot ulceration, present in 78% of diabetic patients with ulcers. 4 The triad of peripheral sensory neuropathy, minor trauma, and foot deformity is present in over 63% of patients with ulcerations. 4

The mechanism involves: 4

• Loss of protective sensation allowing unrecognized trauma from ill-fitting shoes or walking barefoot
• Foot deformities and limited joint mobility causing abnormal biomechanical loading
• High-pressure areas leading to callus formation, subcutaneous hemorrhage, and eventual ulceration
• Continued walking on insensitive feet impairing wound healing

Autonomic Neuropathy

Diabetic neuropathy can also affect autonomic nerves, causing: 4

• Orthostatic hypotension and resting tachycardia
• Gastroparesis with nausea, vomiting, and early satiety
• Genitourinary disturbances including erectile dysfunction, retrograde ejaculation, bladder dysfunction, and female sexual dysfunction
• Dry, cracked skin in the extremities due to impaired sweating

Impact on Quality of Life

Neuropathic pain profoundly impacts quality of life: 5

• Severe sleep disturbance leading to fatigue and reduced daily activities
• Depression and anxiety affecting over two-thirds of patients with painful diabetic neuropathy
• Limitations in daily activities and poor treatment satisfaction

Screening and Diagnosis

When to Screen

All people with type 2 diabetes should be assessed for diabetic peripheral neuropathy starting at diagnosis, and those with type 1 diabetes starting 5 years after diagnosis, with at least annual reassessment thereafter. 4

Clinical Assessment Components

Assessment should include: 4

1. Careful history of symptoms (pain, burning, numbness, tingling)
2. Small-fiber function testing: pinprick sensation and temperature perception on the dorsum of the foot
3. Large-fiber function testing: vibration perception using a 128-Hz tuning fork and assessment of lower-extremity reflexes
4. Protective sensation testing: 10-g monofilament testing annually to identify feet at risk for ulceration and amputation

Important Diagnostic Principle

Diabetic neuropathy is a diagnosis of exclusion. 4 Nondiabetic neuropathies may coexist in people with diabetes and may be treatable. Initial laboratory evaluation should include: 7, 1

• Vitamin B12 with metabolites (methylmalonic acid ± homocysteine)—particularly important in older adults and those on metformin
• Thyroid-stimulating hormone (TSH) to identify hypothyroidism
• Serum protein electrophoresis with immunofixation to detect monoclonal gammopathies
• Complete metabolic panel to assess for renal disease

Electrophysiological testing or neurologist referral is rarely needed except when clinical features are atypical or diagnosis is unclear. 4 Standard nerve conduction studies may be completely normal in small fiber neuropathy, as these tests only evaluate large myelinated fibers. 5

Common Pitfalls

• Assuming absence of symptoms means absence of neuropathy—up to 50% of cases are asymptomatic 4
• Failing to perform annual foot examinations—this is critical for preventing ulcers and amputations 4
• Not investigating reversible causes—vitamin B12 deficiency, hypothyroidism, and monoclonal gammopathies are treatable 7
• Expecting complete reversal with treatment—even with optimal management, complete reversal of nerve damage is uncommon 1