What is the most appropriate initial test to order for a patient with a history of alcohol use disorder, type 2 diabetes mellitus, and progressive pedal pain with tingling sensations, who is taking metformin?

Serum Vitamin B12 Testing is the Most Appropriate Initial Test

Order serum vitamin B12 level now (Option A) for this patient with long-term metformin use, alcohol use disorder, and peripheral neuropathy symptoms. This patient has multiple overlapping risk factors for vitamin B12 deficiency that could be contributing to or exacerbating his neuropathy, and identifying this treatable cause is the immediate priority before pursuing more invasive or expensive testing 1, 2.

Clinical Reasoning for Vitamin B12 Testing

Metformin-Associated B12 Deficiency

• Long-term metformin use (>10 years) is strongly associated with biochemical vitamin B12 deficiency, and the American Diabetes Association explicitly recommends periodic measurement of B12 levels in metformin-treated patients, especially those with anemia or peripheral neuropathy 1.
• The patient's macrocytic anemia (MCV 100.8) and thrombocytopenia (platelet count 121,000) are consistent with B12 deficiency 3.
• Vitamin B12 deficiency compounds neuropathy risk and can worsen diabetic neuropathy symptoms including the burning pain, tingling, and sensory loss this patient exhibits 2, 3.

Alcohol Use Disorder as Additional Risk Factor

• Chronic alcohol use is an independent risk factor for vitamin B12 deficiency through malabsorption and nutritional deficiency 1, 3.
• This patient has dual risk factors (metformin + alcohol), making B12 deficiency highly likely 2.

Diabetic Neuropathy is a Diagnosis of Exclusion

• Before attributing peripheral neuropathy solely to diabetes, alternative causes must be ruled out, including vitamin B12 deficiency, hypothyroidism (already checked and normal), and medication-induced neuropathy 1, 2.
• The American Diabetes Association guidelines specifically list vitamin B12 deficiency among causes to consider in patients with diabetic neuropathy 1.

Why Not the Other Tests Now?

Serum Thiamine (Option B)

• While thiamine deficiency occurs in alcohol use disorder, it typically presents with acute Wernicke encephalopathy or beriberi, not chronic progressive peripheral neuropathy over one year 2.
• The patient's symptoms are chronic and progressive, not acute, making thiamine less likely as the primary etiology.

Lower Extremity Vascular Studies (Option C)

• Palpable pedal pulses make significant peripheral arterial disease unlikely as the cause of his symptoms 1.
• His symptoms are neuropathic (burning, tingling, sensory loss) rather than vascular (claudication, rest pain, absent pulses) 1.
• Vascular studies would be appropriate if pulses were diminished or absent 1.

Electromyography/Nerve Conduction Studies (Option D)

• EMG/NCS are rarely needed except when clinical features are atypical or diagnosis is unclear 1, 4.
• This patient has a typical presentation of distal symmetric polyneuropathy with clear risk factors (diabetes, metformin, alcohol) 1, 4.
• Do not delay treatment waiting for electrodiagnostic studies when the clinical diagnosis is straightforward 2.

Critical Clinical Pitfalls to Avoid

• Do not overlook vitamin B12 deficiency, especially in patients taking metformin, as deficiency compounds neuropathy risk and is readily treatable 2.
• The combination of macrocytic anemia, thrombocytopenia, long-term metformin use, and peripheral neuropathy makes B12 deficiency highly probable 3.
• Metformin should be used cautiously in patients with active alcohol abuse due to increased risk of lactic acidosis, though this patient is currently hospitalized and being offered resources for alcohol use disorder management 5, 6.

Immediate Management Algorithm

1. Order serum vitamin B12 level immediately 1, 2, 3
2. If B12 is low (<180 pg/mL) or borderline (180-350 pg/mL), consider methylmalonic acid level for confirmation 3
3. Continue optimizing glycemic control (current HbA1c 8.1%) to prevent further neuropathy progression 1, 4, 2
4. Initiate first-line neuropathic pain medication (pregabalin, duloxetine, or gabapentin) rather than continuing narcotic analgesics 4, 2
5. Provide comprehensive foot care education and arrange podiatry follow-up given loss of protective sensation 1, 4, 2