What conditions can cause a falsely low glycated hemoglobin (HbA1c) despite fasting plasma glucose of 120–130 mg/dL, and why is HbA1c still used for diabetes diagnosis?

Why Your HbA1c is Falsely Low Despite Elevated Fasting Glucose

Your HbA1c of 4.1% is falsely low and does not reflect your true glycemic control, which is actually indicated by your fasting glucose readings of 120-130 mg/dL—this discrepancy is most commonly caused by conditions that shorten red blood cell lifespan, making HbA1c unreliable for your diabetes management. 1, 2

Understanding the Discrepancy

Your situation represents a classic example of HbA1c underestimating true glycemic control. Here's why this happens:

• Any condition that shortens RBC survival or decreases mean RBC age produces falsely low HbA1c results regardless of the assay method used. 3, 2 Your red blood cells aren't living long enough to accumulate the glucose that would normally attach to hemoglobin over their typical 120-day lifespan.

• Your fasting glucose of 120-130 mg/dL is the more accurate reflection of your glycemic status, as glucose measurements are not affected by red blood cell turnover. 1, 2

Common Causes of Falsely Low HbA1c

Your endocrinologist should investigate these specific conditions:

Conditions Affecting Red Blood Cell Lifespan (Most Common)

• Hemolytic anemia (any cause) results in falsely low HbA1c because red blood cells have less time for glucose exposure and glycation. 4, 5

• Chronic kidney disease can shorten erythrocyte lifespan, resulting in falsely low values—this is particularly common and often overlooked. 3, 4, 6

• Recovery from acute blood loss falsely lowers HbA1c by reducing mean RBC age. 4, 2

• Chronic liver disease with splenomegaly causes hypersplenism, which increases red blood cell turnover and destruction. 7

• Pregnancy (if applicable) alters RBC turnover, lowering usual HbA1c concentrations. 4, 2

Hemoglobin Variants

• Hemoglobin variants (HbS, HbC, HbE) can result in falsely elevated or falsely lowered HbA1c levels depending on the specific assay method used. 2 This is particularly important in Southeast Asian and Mediterranean populations. 4

Nutritional and Medication Factors

• Vitamins C and E are reported to falsely lower HbA1c results, possibly by inhibiting glycation of hemoglobin. 3, 2

Essential Diagnostic Workup

Your physician should order these specific tests immediately: 1

• Complete blood count (CBC) to assess for anemia and hemolysis 1, 2
• Reticulocyte count to evaluate red blood cell turnover 1, 4
• Iron studies to evaluate for iron deficiency (which paradoxically causes falsely high HbA1c) 1, 2
• Hemoglobin electrophoresis if hemoglobin variant is suspected 1, 4
• Kidney function tests (creatinine, eGFR) to assess for chronic kidney disease 3, 6
• Liver function tests if chronic liver disease is suspected 7

Why HbA1c is Still Used for Diabetes Diagnosis

Despite these limitations, HbA1c remains the standard because:

• HbA1c is accurate for the vast majority of people who don't have conditions affecting red blood cell turnover. 3, 1

• It reflects average glycemia over 2-3 months without requiring fasting, making it convenient and less affected by day-to-day glucose fluctuations. 3

• All HbA1c assays in the U.S. are standardized through the National Glycohemoglobin Standardization Programme (NGSP), ensuring consistency across laboratories. 8

• The conditions that cause false results are identifiable and manageable when clinicians are aware of them. 3, 1

What You Should Do Now

Immediate Actions:

• Use your fasting glucose readings (120-130 mg/dL) as your primary indicator of glycemic control, not the HbA1c of 4.1%. 1, 2

• Request the diagnostic workup listed above to identify the underlying cause of your falsely low HbA1c. 1

• Repeat HbA1c using the same laboratory method to rule out laboratory error, while simultaneously obtaining fasting plasma glucose for comparison. 1

Alternative Monitoring Strategies:

• Switch to fructosamine or glycated albumin testing, which reflects 2-3 weeks of glycemic control and is unaffected by RBC disorders. 1, 4 However, these are less widely available and have their own limitations in kidney disease. 3

• Implement continuous glucose monitoring (CGM), which provides comprehensive glycemic patterns and identifies missed excursions without being affected by red blood cell issues. 1, 2

• Rely on self-monitored blood glucose (SMBG) for treatment decisions, particularly insulin dosing, as this directly measures glucose without interference from red blood cell abnormalities. 3, 6

Critical Pitfalls to Avoid

• Never base treatment decisions solely on your HbA1c of 4.1%, as this may lead to undertreatment of your diabetes. 2 Your fasting glucose indicates you likely need treatment intensification, not reassurance.

• Don't dismiss the discrepancy as laboratory error without proper investigation—this represents a real physiological issue that needs identification. 1, 4

• Once a reliable monitoring method is established (whether alternative HbA1c method, fructosamine, or CGM), don't switch between different methods for serial monitoring, as this introduces additional measurement variability. 2

Special Considerations

• If you have chronic kidney disease, the correlation between HbA1c and actual glucose levels weakens significantly, particularly if you also have anemia. 6 In one study, the correlation coefficient dropped from 0.70 in people without CKD to 0.35 in those with severe CKD and anemia. 6

• Age may play a minor role: HbA1c increases approximately 0.1% per decade after age 30 in people without diabetes, but this doesn't explain your dramatically low value. 3, 2

• If you're taking high-dose vitamin C or E supplements, consider stopping them temporarily to see if HbA1c normalizes. 3, 2