Can diabetes cause painful peripheral neuropathy?

Does Diabetes Cause Painful Peripheral Neuropathy?

Yes, diabetes directly causes painful peripheral neuropathy (painful DPN), affecting 10-26% of people with diabetes, with the overall prevalence of diabetic peripheral neuropathy reaching up to 50% during their lifetime. 1, 2

Epidemiology and Prevalence

• Painful diabetic peripheral neuropathy affects 16% of the diabetic population based on population-based studies, though prevalence estimates range from 10-26% depending on the study methodology 1
• Nearly 50% of adults with diabetes will develop some form of peripheral neuropathy during their lifetime, though not all will experience pain 2
• Alarmingly, 12.5% of patients with painful DPN never report their symptoms to their doctor, and 39% never receive treatment for their pain, highlighting significant underdiagnosis and undertreatment 1

Pathophysiological Mechanisms

Diabetes causes painful peripheral neuropathy through multiple interconnected mechanisms:

Metabolic and Vascular Pathways

• Hyperglycemia and metabolic imbalances lead to oxidative stress and inflammation, resulting in degeneration of C and Aδ nerve fibers 3
• Poor or erratic glycemic control contributes to the genesis of neuropathic pain, with observational studies suggesting that blood glucose fluctuations intensify pain symptoms 1
• Dysfunction of the microvasculature supporting the nerves exacerbates neural damage, with altered peripheral nerve epineurial blood flow and foot skin microcirculation 1, 3

Neurological Changes

• Reduced intra-epidermal nerve fiber density (ENFD) occurs in early neuropathy, with the longest axons typically damaged first, explaining why DPN normally begins in the feet 1, 3
• Changes in sodium and calcium channel distribution and expression contribute to peripheral sensitization 1
• Central sensitization occurs, with Aβ fiber sprouting into lamina II of the dorsal horn and reduced inhibition via descending pathways 1

Clinical Presentation

Typical Characteristics

• Painful DPN presents with distal, symmetrical symptoms associated with nocturnal exacerbation 1
• Common pain descriptors include burning, shooting, stabbing, and electric shock-like sensations 1
• On examination, there is usually blunting of sensation in the feet, though occasionally in acute painful DPN, symptoms may be present without signs 1

Special Clinical Variant

• Acute painful DPN can follow rapid changes in glycemic control, either from sudden improvement (historically termed "insulin neuritis") or after episodes of very poor control like diabetic ketoacidosis 1
• The prognosis of acute painful DPN is good, with complete resolution usually occurring within one year 1

Important Clinical Caveats

• Painful DPN is invariably symmetrical; patients with asymmetrical symptoms should be carefully assessed for other etiologies such as entrapment syndromes, peripheral vascular disease, arthritis, malignancy, alcohol abuse, or spinal canal stenosis 1
• Diabetic neuropathy is a diagnosis of exclusion, requiring careful clinical history and peripheral neurological and vascular examination to rule out other causes 1
• Nerve conduction studies are particularly important to exclude other causes of pain, such as entrapment syndromes 1

Risk Factors Beyond Diabetes

• Duration of diabetes, poor glucose control, and type of diabetes (type 1 versus type 2) all influence prevalence 2
• Other cardiovascular risk factors including hypertension and hyperlipidemia contribute to DPN development and progression 1, 4
• Vitamin B12 deficiency and obesity are modifiable risk factors that should be addressed 5