What is the recommended workup for a 52-year-old male with hyperglycemia (elevated A1c), elevated immunoglobulin G (IgG) and immunoglobulin E (IgE) levels, and erythrocytosis (elevated red blood cell count), currently on insulin (118 units daily), Glipizide (a sulfonylurea) and Synjardy (Empagliflozin and Metformin)?

Recommended Workup for Severely Uncontrolled Diabetes with Elevated Immunoglobulins and Erythrocytosis

This patient requires immediate diabetes treatment intensification given the A1c of 11.4%, and a focused workup to evaluate the elevated immunoglobulins and erythrocytosis, which may represent concurrent conditions affecting diabetes management or complications.

Immediate Diabetes Management Priority

The A1c of 11.4% represents severely uncontrolled diabetes requiring urgent treatment intensification—this should not be delayed while pursuing other workups. 1

• Increase basal insulin by 2-4 units every 3-7 days until fasting glucose reaches 80-130 mg/dL target 1, 2
• Add prandial insulin starting with 4 units at the largest meal, as the current regimen of 118 units daily insulin plus glipizide and Synjardy is clearly insufficient 1, 2
• Consider discontinuing glipizide when moving to more complex insulin regimens, as sulfonylureas significantly increase hypoglycemia risk when combined with intensive insulin therapy 2, 3
• Add a GLP-1 receptor agonist (such as semaglutide or dulaglutide) to the current regimen, which can provide an additional 1-2% A1c reduction with cardiovascular benefits and potential to reduce insulin requirements by 10-20% 1, 4

Workup for Elevated Immunoglobulins

IgG Elevation (1847 mg/dL)

Evaluate for chronic inflammatory conditions, autoimmune disorders, and infections:

• Serum protein electrophoresis (SPEP) with immunofixation to rule out monoclonal gammopathy or multiple myeloma, particularly important given the age and concurrent laboratory abnormalities [@General Medicine Knowledge]
• Complete metabolic panel including liver function tests, as chronic liver disease can cause polyclonal hypergammaglobulinemia [@General Medicine Knowledge]
• Antinuclear antibody (ANA), rheumatoid factor, and anti-CCP antibodies to screen for autoimmune conditions [@General Medicine Knowledge]
• HIV testing, hepatitis B and C serologies, as chronic infections commonly cause elevated IgG [@General Medicine Knowledge]
• Quantitative immunoglobulin subclasses (IgG1-4) if SPEP shows polyclonal pattern [@General Medicine Knowledge]

IgE Elevation (1713 IU/mL)

Investigate allergic, parasitic, and immunologic causes:

• Complete blood count with differential to assess for eosinophilia, which often accompanies elevated IgE [@General Medicine Knowledge]
• Stool ova and parasites examination (three samples), as parasitic infections are a common cause of marked IgE elevation [@General Medicine Knowledge]
• Allergic evaluation including specific IgE testing if clinical history suggests atopy or allergic bronchopulmonary aspergillosis [@General Medicine Knowledge]
• Consider evaluation for hyper-IgE syndrome if recurrent infections, eczema, or skeletal abnormalities are present [@General Medicine Knowledge]

Workup for Erythrocytosis (RBC 6.96 million/μL)

Determine if this represents primary polycythemia or secondary erythrocytosis:

• Hemoglobin, hematocrit, and complete blood count to confirm true erythrocytosis versus relative polycythemia from volume depletion [@General Medicine Knowledge]
• Arterial blood gas or pulse oximetry to assess for hypoxemia-driven erythropoiesis [@General Medicine Knowledge]
• Serum erythropoietin level—low levels suggest polycythemia vera, while elevated levels indicate secondary causes [@General Medicine Knowledge]
• JAK2 V617F mutation testing if erythropoietin is low or normal, as this is present in >95% of polycythemia vera cases [@General Medicine Knowledge]
• Renal ultrasound to evaluate for renal masses or cysts that can produce erythropoietin [@General Medicine Knowledge]
• Sleep study evaluation if clinical suspicion for obstructive sleep apnea, which commonly causes secondary erythrocytosis and worsens diabetes control [@General Medicine Knowledge]

Additional Diabetes-Related Workup

Given the severe hyperglycemia and African American ethnicity, evaluate for complications and cardiovascular risk:

• Comprehensive metabolic panel including creatinine and eGFR, as the patient is on Synjardy (empagliflozin/metformin) which requires renal function monitoring [@1@, 1]
• Urine albumin-to-creatinine ratio to assess for diabetic nephropathy 1
• Lipid panel, as cardiovascular risk stratification is essential with this degree of hyperglycemia [@1@, 1]
• Dilated retinal examination to screen for diabetic retinopathy 1
• Electrocardiogram and consider cardiovascular assessment, as African American patients with diabetes have higher cardiovascular risk 1

Critical Monitoring During Treatment Intensification

With insulin intensification and multiple laboratory abnormalities:

• Home blood glucose monitoring 4-7 times daily (fasting, pre-meals, 2 hours post-meals, bedtime) to guide insulin titration [@4@, 2]
• Prescribe glucagon for emergency hypoglycemia management, especially given the high insulin doses and addition of prandial insulin [@7@, @8@]
• Reassess A1c in 3 months—if still >8%, further intensification is required [@1@, 1,2]
• Monitor for hypoglycemia closely when combining high-dose insulin with glipizide; strongly consider discontinuing glipizide 2, 3
• Recheck complete blood count in 4-6 weeks after initiating workup to monitor erythrocytosis trend [@General Medicine Knowledge]

Common Pitfalls to Avoid

Do not delay diabetes treatment intensification while pursuing the immunoglobulin and erythrocytosis workup—the A1c of 11.4% requires immediate action to prevent metabolic decompensation and complications. 1, 2

Avoid continuing glipizide when intensifying to multiple daily insulin injections, as this combination dramatically increases hypoglycemia risk without meaningful additional benefit. 2, 3

Do not assume the elevated immunoglobulins are incidental—polyclonal hypergammaglobulinemia and markedly elevated IgE warrant systematic evaluation for underlying conditions that may also impact diabetes management. [@General Medicine Knowledge]

Recognize that erythrocytosis can increase blood viscosity and cardiovascular risk, which is particularly concerning in a patient with severe diabetes and likely existing microvascular disease. [@General Medicine Knowledge]

Ensure metformin component of Synjardy is not contraindicated if renal function is impaired (eGFR <30 mL/min/1.73m²), as this is common with severe long-standing hyperglycemia. 1