What is the most appropriate initial test for a patient with a history of alcohol use disorder, type 2 diabetes mellitus, and progressive pedal pain with tingling sensations, who has been taking metformin for over 10 years?

Serum Vitamin B12 Testing is the Most Appropriate Initial Test

Order serum vitamin B12 level now (Option A) for this patient with >10 years of metformin use presenting with peripheral neuropathy symptoms. 1, 2

Rationale for Vitamin B12 Testing

Metformin-Associated B12 Deficiency

• Long-term metformin use (>10 years in this patient) 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, 2
• This patient has both risk factors warranting B12 testing: macrocytic anemia (MCV 100.8) and peripheral neuropathy symptoms (burning pain, tingling, diminished sensation). 1
• The effect of metformin on vitamin B12 increases with time, with higher risk for deficiency noted at 4-5 years, making this patient at particularly high risk after 10+ years of therapy. 1

Multiple Compounding Risk Factors

• Chronic alcohol use disorder is an independent risk factor for vitamin B12 deficiency through malabsorption and nutritional deficiency, compounding the metformin effect. 2
• The combination of metformin use, alcohol use disorder, and macrocytic anemia creates a high-probability scenario for B12 deficiency. 2, 3

Clinical Presentation Consistent with B12 Deficiency

• Vitamin B12 deficiency compounds neuropathy risk and can worsen diabetic neuropathy symptoms, including burning pain, tingling, and sensory loss—all present in this patient. 2
• Before attributing peripheral neuropathy solely to diabetes, alternative treatable causes must be ruled out, with vitamin B12 deficiency specifically listed by the American Diabetes Association. 2, 4

Why Not the Other Options

Serum Thiamine (Option B)

• While thiamine deficiency occurs in alcohol use disorder, this patient's presentation is more consistent with chronic peripheral neuropathy (>1 year duration) rather than acute Wernicke encephalopathy or beriberi. 2
• Thiamine deficiency typically presents with acute neurologic changes, cardiovascular symptoms, or Wernicke's triad—none of which are described here. 2
• B12 deficiency is the more likely culprit given the metformin use, macrocytic anemia, and chronic neuropathy pattern. 1, 2

Lower Extremity Vascular Studies (Option C)

• Palpable pedal pulses make significant peripheral arterial disease unlikely as the cause of neuropathic symptoms. 2
• The burning, tingling quality with sensory changes is characteristic of neuropathy, not vascular claudication. 2, 4
• Vascular studies would be indicated if pulses were absent or if symptoms suggested claudication. 2

EMG/Nerve Conduction Studies (Option D)

• EMG/NCS are rarely needed except when clinical features are atypical or diagnosis is unclear. 2
• This patient has a straightforward presentation of distal symmetric polyneuropathy with clear risk factors (diabetes, metformin, alcohol). 2, 4
• EMG/NCS would not change immediate management and should be reserved for atypical presentations. 2

Additional Management Considerations

Immediate Actions Beyond B12 Testing

• Continue optimizing glycemic control (current A1C 8.1%) to prevent further neuropathy progression. 2, 4
• Initiate first-line neuropathic pain medication (pregabalin, duloxetine, or gabapentin) rather than continuing narcotic analgesics, which are not recommended for diabetic neuropathy. 2, 4
• Provide comprehensive foot care education given loss of protective sensation (diminished vibration and pinprick). 2, 4

Metformin Safety in This Patient

• Note the contraindication: active alcohol abuse is listed as a contraindication to metformin due to increased risk of metformin-associated lactic acidosis (MALA). 5, 6
• This patient with active alcohol use disorder and recent alcohol intoxication requiring hospitalization should have metformin safety reassessed. 5, 6
• Ensure adequate renal function (eGFR ≥30 mL/min/1.73 m²) before continuing metformin. 1, 6