What does a low Hemoglobin A1c (HbA1c) level indicate?

Understanding Low HbA1c Levels

A low Hemoglobin A1c (HbA1c) level below 5.7% typically indicates normal glucose metabolism and absence of diabetes, but can also reflect certain pathological conditions that affect erythrocyte lifespan or hemoglobin structure.

Normal HbA1c Ranges and Interpretation

HbA1c reflects average blood glucose levels over the previous 2-3 months, with normal values defined as:

• Normal: <5.7%
• Prediabetes: 5.7-6.4%
• Diabetes: ≥6.5% 1

The correlation between HbA1c and mean plasma glucose is approximately:

• 6% HbA1c = 126 mg/dL mean plasma glucose
• 7% HbA1c = 154 mg/dL mean plasma glucose
• 8% HbA1c = 183 mg/dL mean plasma glucose 2

Causes of Abnormally Low HbA1c

When HbA1c is unexpectedly low relative to blood glucose measurements or clinical presentation, consider these potential causes:

1. Conditions Affecting Red Blood Cell Lifespan

• Hemolytic anemia - shortened erythrocyte lifespan reduces glycation time 3
• Acute or chronic blood loss
• Kidney disease - uremia shortens RBC survival
• Liver disease - affects RBC production and survival
• Recovery from blood loss 1

2. Hemoglobinopathies and Variants

• Hemoglobin S or C carriers - may have spuriously high or low HbA1c results with certain assay methods 1
• Other hemoglobin variants (over 700 reported) can affect results 1

3. Medications and Supplements

• Erythropoietin-stimulating agents - increase production of new RBCs 1
• Iron supplements - correction of iron deficiency anemia 1
• Vitamins C and E - may lower HbA1c by inhibiting glycation 1

4. Physiological States

• Pregnancy - lower HbA1c levels are found in both diabetic and non-diabetic pregnant women 1

Clinical Implications of Low HbA1c

For Non-Diabetic Patients

• A low HbA1c (<5.7%) in the absence of symptoms or other abnormal findings generally indicates normal glucose metabolism
• May serve as a screening indicator for hemolytic processes in patients without diabetes 3

For Diabetic Patients

• Discrepancy between HbA1c and blood glucose readings should prompt investigation for conditions affecting RBC lifespan
• HbA1c is considered a poor marker for overall glycemia in diabetic patients with hemolytic disease 3

Alternative Glycemic Markers When HbA1c is Unreliable

When HbA1c is suspected to be inaccurate:

• Fructosamine - reflects glycemia over 2-4 weeks (though reliability is variable) 1
• Glycated albumin - reflects glycemia over 2-4 weeks, but affected by hypoalbuminemia 1
• Self-monitoring blood glucose (SMBG) - provides point-of-care measurements but may underestimate glucose excursions 4
• Continuous glucose monitoring (CGM) - provides more comprehensive glycemic data 4

Diagnostic Approach to Unexpectedly Low HbA1c

When HbA1c is surprisingly low:

1. Verify with repeat testing using a different assay method if available
2. Consider boronate affinity chromatography method for HbA1c measurement if hemoglobin variant is suspected 1
3. Evaluate for hemolysis (CBC, reticulocyte count, haptoglobin, LDH)
4. Screen for hemoglobinopathies if clinically indicated
5. Review medication list for agents that may affect RBC lifespan or HbA1c formation

Clinical Pitfalls to Avoid

• Don't assume excellent glycemic control in diabetic patients with unexpectedly low HbA1c without confirming with other glycemic measures
• Don't overlook potential hemolytic processes when HbA1c is disproportionately low compared to blood glucose readings
• Don't rely solely on HbA1c for glycemic assessment in patients with conditions affecting RBC lifespan or hemoglobin structure
• Be aware of assay limitations - different HbA1c measurement methods may be affected differently by hemoglobin variants 1