What causes the discrepancy between my elevated HbA1C and CGM GMI?

Discrepancy Between HbA1c and CGM GMI: Causes and Next Steps

The discrepancy between your elevated HbA1c (9.1%) and lower CGM GMI (7.3%) is most likely due to conditions affecting red blood cell turnover or hemoglobin variants, and requires further investigation of potential interfering factors while using the CGM data as your more reliable glycemic marker. 1

Understanding the Discrepancy

A significant difference between HbA1c and CGM-derived Glucose Management Indicator (GMI) is common and clinically important. In your case:

• HbA1c: 9.1% (suggests poor glycemic control)
• CGM GMI: 7.3% (suggests moderate glycemic control)
• Difference: 1.8% (significant clinical discordance)

Normal Lab Values Context

• Your hemoglobin (15.6), GFR (101), liver function (AST/ALT 18/21), and protein levels (total protein 6, albumin 4) are within normal ranges, which rules out some but not all potential causes of discrepancy.

Potential Causes of Discrepancy

1. Conditions Affecting Red Blood Cell Lifespan

• Hemolytic conditions can cause falsely low HbA1c 1, 2
• Recent blood transfusions (within 2-3 months) 2
• Medications that affect erythropoiesis 1

2. Hemoglobin Variants

• Over 700 hemoglobin variants can interfere with HbA1c measurements 2
• Different assay methods have varying susceptibility to interference 2

3. Other Potential Factors

• Ethnicity (African Americans may have higher HbA1c for same glucose levels) 1, 2
• Obesity and type 2 diabetes can increase HbA1c-GMI discordance 3
• Glucose variability not captured by intermittent glucose monitoring 1

Next Steps for Evaluation

1. Evaluate for hemoglobin variants:

   • Request hemoglobin electrophoresis to identify potential variants 2
   • Check if your HbA1c assay method is affected by common variants 2

2. Assess for conditions affecting red blood cell turnover:

   • Complete blood count with reticulocyte count
   • Peripheral blood smear
   • Haptoglobin, LDH, and bilirubin to evaluate for hemolysis

3. Review medication history:

   • Identify medications that might affect red blood cell lifespan
   • Consider recent changes in medications

4. Validate CGM accuracy:

   • Compare CGM readings with fingerstick blood glucose measurements
   • Ensure proper CGM calibration and placement

5. Consider alternative glycemic markers:

   • Fructosamine (reflects 2-3 week glycemic control) 2
   • Glycated albumin (less affected by red blood cell lifespan) 2

Clinical Decision Making

When to Trust CGM GMI Over HbA1c

• When conditions affecting red blood cell turnover are present 1, 2
• When hemoglobin variants are identified 2
• When CGM data shows consistent patterns over multiple weeks 1

When to Trust HbA1c Over CGM GMI

• When CGM wear time is <70% (your 3-month data appears adequate) 3
• When CGM placement or calibration issues are identified

Practical Recommendations

1. Continue using CGM for management decisions while investigating the discrepancy

   • Your consistent GMI of 7.3% over both 2 weeks and 3 months suggests reliable CGM data 1

2. Request a different HbA1c assay method that may be less susceptible to interference

   • Boronate affinity chromatography methods may be more reliable with hemoglobin variants 2

3. Discuss with your healthcare provider about setting treatment targets based on CGM metrics rather than HbA1c alone

   • Time in Range (70-180 mg/dL)
   • Mean glucose values
   • Glycemic variability measures

4. Schedule follow-up testing in 3 months with both HbA1c and CGM data to reassess the discrepancy

Important Caveats

• Studies show that 22-49% of patients have HbA1c-GMI discordance >1% 4, 5
• The GMI formula was primarily developed in type 1 diabetes populations and may be less accurate in type 2 diabetes 6
• Recent research suggests using mean glucose directly rather than converting to GMI may be preferable 7
• The American Diabetes Association recommends using multiple methods to assess glycemic control when HbA1c reliability is questionable 1, 2