Endocrinology · Diabetic Complications
The facts most likely to be tested
The most common form of diabetic neuropathy is distal symmetric polyneuropathy, presenting as a length-dependent, 'stocking-glove' sensory loss.
Initial screening for diabetic neuropathy should begin at the time of Type 2 diabetes diagnosis and 5 years after Type 1 diabetes diagnosis using a 10-gram monofilament test.
Tight glycemic control is the only intervention proven to slow the progression of diabetic peripheral neuropathy.
First-line pharmacologic treatment for painful diabetic neuropathy includes pregabalin or duloxetine.
Diabetic autonomic neuropathy frequently manifests as gastroparesis, characterized by early satiety, postprandial vomiting, and delayed gastric emptying.
Orthostatic hypotension and resting tachycardia are classic clinical indicators of cardiovascular autonomic neuropathy.
Mononeuropathy multiplex or cranial nerve palsies (specifically CN III) in a diabetic patient typically present with pupillary sparing due to microvascular ischemia.
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A 62-year-old male with a 15-year history of poorly controlled Type 2 diabetes presents to the clinic complaining of burning pain in both feet that worsens at night. Physical examination reveals diminished sensation to light touch in a stocking-glove distribution and an absent ankle jerk reflex bilaterally. The patient's 10-gram monofilament test is abnormal on both feet. He has no history of trauma or recent infections.
What is the most appropriate initial pharmacologic therapy for this patient's neuropathic pain?
Pregabalin or Duloxetine
The patient presents with classic distal symmetric polyneuropathy; per guidelines, pregabalin or duloxetine are the first-line agents for managing neuropathic pain in diabetic patients.
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Etiology / Epidemiology
Chronic hyperglycemia causes metabolic nerve damage; risk correlates with duration of diabetes and A1c levels.
Clinical Manifestations
Symmetric distal sensory loss (stocking-glove) and paresthesias; loss of ankle reflexes is a pathognomonic early sign.
Diagnosis
Clinical diagnosis via monofilament testing; electromyography (EMG) is the gold standard for nerve conduction studies.
Treatment
Pregabalin or Duloxetine are first-line; avoid opioids due to addiction risk and lack of efficacy.
Prognosis
High risk of foot ulceration and amputation; annual comprehensive foot exam is mandatory.
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Epidemiology & Etiology
Prevalence increases with duration of diabetes and poor glycemic control. It is the most common cause of neuropathy in developed nations. Patients with Type 2 DM may present with neuropathy at the time of diagnosis.
Pertinent Anatomy
Affects the distal peripheral nerves first due to the length-dependent nature of the disease. Autonomic involvement targets the vagus nerve and sympathetic chain, leading to systemic dysfunction.
Pathophysiology
Chronic hyperglycemia leads to the accumulation of sorbitol via the polyol pathway, causing osmotic stress. Advanced glycation end-products (AGEs) damage microvasculature, resulting in nerve ischemia. Oxidative stress further impairs nerve conduction velocity.
Clinical Manifestations
Patients report stocking-glove sensory loss, burning pain, and nocturnal exacerbation. Physical exam reveals diminished vibration sense and absent ankle jerks. Red flags include asymmetric weakness or rapid onset, which suggest mononeuritis multiplex or radiculopathy.
Diagnosis
Diagnosis is primarily clinical using a 10-g monofilament to assess protective sensation. Electromyography (EMG) and nerve conduction studies are the gold standard to confirm axonal loss. Screen annually using A1c monitoring and physical foot inspection.
Treatment
First-line pharmacotherapy includes Pregabalin or Duloxetine for neuropathic pain. Avoid opioids due to high abuse potential and poor long-term outcomes. Tricyclic antidepressants like Amitriptyline are alternatives but carry anticholinergic side effects in the elderly.
Prognosis
Poorly managed neuropathy leads to Charcot joint (neuropathic arthropathy) and non-healing foot ulcers. Annual comprehensive foot exams are required to prevent secondary infection and amputation.
Differential Diagnosis
Vitamin B12 deficiency: presents with dorsal column involvement (proprioception loss)
Alcoholic neuropathy: usually associated with nutritional deficiencies and proximal muscle wasting
Guillain-Barre syndrome: rapid, ascending paralysis following infection
Lyme disease: associated with radiculopathy and history of tick exposure
Uremic neuropathy: correlates with elevated BUN/Creatinine levels