Understanding Your Discordant A1C and Glucose Values
Your A1C of 4.1% is falsely low and does not reflect your true glycemic status, given your fasting glucose consistently measures 120-130 mg/dL—this discordance indicates a condition affecting red blood cell turnover or a hemoglobin variant is interfering with your A1C measurement. 1
Why Your A1C is Unreliable
Several conditions cause falsely low A1C values despite elevated glucose levels:
Conditions with Increased Red Blood Cell Turnover
These shorten the lifespan of red blood cells, preventing adequate glycation time:
- Hemolytic anemias (any cause) 1
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency - can lower A1C by 0.7-0.8% in homozygous individuals 1
- Recent blood loss or transfusion 1
- Hemodialysis 1
- Erythropoietin therapy 1
- Pregnancy (second and third trimesters) 1
- Beta-thalassemia minor - particularly when associated with increased red cell turnover 2, 3
- Liver cirrhosis with associated hematologic changes 4
Hemoglobin Variants
These interfere with A1C measurement by the assay itself:
- Sickle cell trait (HbS) - lowers A1C by approximately 0.3% 1
- Rare hemoglobin variants (Hb Iraq-Halabja, Hb J-Bangkok, Hb Riyadh) - can cause spuriously low readings on standard HPLC assays 5, 3, 6
- Hemoglobin C trait 1
Other Interfering Conditions
- High-dose vitamin C or E supplementation - may inhibit glycation 1
- Certain medications affecting red cell turnover 7
What You Should Do Next
Immediate Diagnostic Steps
Request a complete blood count (CBC) with reticulocyte count to assess for hemolytic anemia or increased red cell turnover 2, 3
Check hemoglobin electrophoresis to identify hemoglobin variants that may be interfering with your A1C assay 1, 3
Consider G6PD testing if you have African, Mediterranean, or Asian ancestry 1
Measure glycated albumin or fructosamine as alternative glycemic markers unaffected by red cell turnover 2, 3
Review your A1C chromatogram - abnormal peaks suggest hemoglobin variants 3
For Ongoing Monitoring
Use fasting plasma glucose and postprandial glucose measurements exclusively for diabetes diagnosis and monitoring in your case, as the American Diabetes Association explicitly recommends plasma glucose criteria when A1C is unreliable. 1
Your fasting glucose of 120-130 mg/dL places you in the prediabetes range (100-125 mg/dL is prediabetes; ≥126 mg/dL on two occasions confirms diabetes). 1
Why A1C is Still Used Despite These Limitations
A1C remains the standard because:
- Greater convenience - no fasting required 1
- Better pre-analytical stability - less affected by acute stress or illness 1
- Strong correlation with microvascular complications in most patients 1
- Reflects 2-3 month average rather than single time point 1
- Standardized assays (NGSP-certified) provide reliable results in 99% of patients without interfering conditions 1
However, the guidelines are clear: when marked discrepancies exist between A1C and plasma glucose levels, the A1C assay should not be considered reliable for that individual, and glucose-based criteria must be used exclusively. 1
Critical Clinical Pitfalls to Avoid
- Do not rely on A1C alone when it conflicts dramatically with glucose measurements—your situation is a textbook example of when A1C fails 1
- Do not assume normal A1C means normal glucose control in the presence of conditions affecting red cell turnover 2, 3, 4
- Do not use point-of-care A1C devices for diagnosis—only laboratory NGSP-certified assays are acceptable, and even these fail in your situation 1, 8
- Do not delay investigation of extremely low A1C (<4.0%) as it may indicate underlying hematologic or liver disease requiring attention 4
Your endocrinologist correctly identified this discordance. The next step is determining which specific condition is causing your falsely low A1C through the diagnostic workup outlined above.