Overview
This lecture explores the various types of diabetic neuropathies, covering their classifications, clinical features, underlying mechanisms, and diagnostic approaches.
Classification and Epidemiology of Diabetic Neuropathies
- Diabetic neuropathies are classified as symmetric (e.g., distal sensory) or asymmetric (e.g., radiculoplexus).
- Most common types are distal sensory neuropathy (DSN), distal small fiber neuropathy (DSFN), and diabetic autonomic neuropathy (DAN).
- Up to two-thirds of diabetic patients have objective evidence of neuropathy, but only 20% have symptoms.
- Main causes include hyperglycemia, microvascular disease, hypertriglyceridemia, and genetic/immune factors.
Distal Sensory and Small Fiber Neuropathies
- DSN starts after about 10 years of diabetes, affecting large myelinated sensory fibers and often asymptomatic.
- Symptoms of DSN include loss of vibration sense, hypesthesia, and sometimes pain.
- DSFN affects unmyelinated small fibers; presents as burning, prickling, or stabbing pain in feet.
- DSFN is diagnosed using QSART and skin biopsy to assess intraepidermal nerve fibers.
Diabetic Autonomic Neuropathy (DAN)
- DAN involves diverse autonomic symptoms: orthostatic hypotension, cardiac autonomic neuropathy, gastroparesis, neurogenic bladder, and erectile dysfunction.
- Cardiac autonomic neuropathy increases mortality risk and can cause silent myocardial ischemia.
- Gastrointestinal symptoms range from gastroparesis to constipation and diarrhea.
- DAN leads to thermoregulatory issues, sweating abnormalities, and pupillary dysfunction.
Natural History, Prognosis, and Autoimmune Forms
- Autonomic deficits worsen over diabetes duration—clinical failure occurs in about 5% after 10-15 years.
- DAN raises risk of sudden cardiac death and is linked to QT interval prolongation.
- Autoimmune forms include chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and autoimmune autonomic ganglionopathy (AAG), requiring distinct diagnosis and sometimes immunotherapy.
Diabetic Radiculoplexus Neuropathy
- Subacute onset with proximal pain, muscle weakness, significant weight loss, and autonomic failure.
- Pathology shows axonal loss, ischemia, microvasculitis, and inflammatory markers.
- Electromyography reveals active muscle denervation; some patients respond to steroids or immunotherapy.
Treatment-Induced Diabetic Neuropathy (TIND)
- TIND is acute, painful small fiber neuropathy after rapid glycemic control (A1c drop).
- Manifests within weeks, with both pain and autonomic failure, usually reversible after stabilization.
- Proposed mechanisms include ischemia, hypoxia of unmyelinated fibers, and energy crisis in nerves.
Key Terms & Definitions
- Distal Sensory Neuropathy (DSN) — Neuropathy affecting large myelinated sensory fibers, often distal and symmetric.
- Distal Small Fiber Neuropathy (DSFN) — Neuropathy affecting small unmyelinated fibers, characterized by burning pain.
- Diabetic Autonomic Neuropathy (DAN) — Widespread dysfunction of autonomic nerves in diabetes.
- Radiculoplexus Neuropathy — Acute/subacute neuropathy with proximal weakness and pain, related to plexus and nerve root involvement.
- Treatment-Induced Diabetic Neuropathy (TIND) — Painful neuropathy triggered by rapid blood glucose normalization.
- QSART — Quantitative Sudomotor Axon Reflex Test for small fiber function.
- IENF density — Measure of intraepidermal nerve fibers in skin biopsy for small fiber neuropathy.
Action Items / Next Steps
- Review classification tables of diabetic neuropathies for exam reference.
- Study diagnostic criteria and testing methods (e.g., QSART, skin biopsy, nerve conduction studies).
- Familiarize with autonomic and sensory symptoms and their clinical significance.