What causes low Hemoglobin A1c (HbA1c) with normal blood glucose levels?

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From the Guidelines

Low Hemoglobin A1c (HbA1c) with Normal Blood Glucose Levels

Low HbA1c levels with normal blood glucose levels can be caused by several factors, including recent blood transfusions, hemolytic anemia, or certain medications such as erythropoietin 1.

Conditions Affecting HbA1c Levels

Some conditions that can affect HbA1c levels include:

  • Iron deficiency anemia 1
  • Vitamin B12 or folate deficiency
  • Chronic liver or kidney disease 1
  • Pregnancy 1
  • Glucose-6-phosphate dehydrogenase deficiency 1
  • Hemodialysis 1
  • Recent blood loss 1
  • Erythropoietin therapy 1
  • Sickle cell disease 1
  • HIV treated with certain protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs) 1

Importance of Healthcare Provider Consultation

It's essential to consult with your healthcare provider to determine the underlying cause of low HbA1c levels and develop a personalized plan to address it 1. In some cases, your healthcare provider may recommend monitoring your HbA1c levels more frequently or adjusting your treatment plan to ensure your blood sugar levels remain within a healthy range.

From the Research

Factors Affecting HbA1c Levels

  • HbA1c levels can be influenced by various factors, including red blood cell lifespan, hemolysis, and the presence of certain hemoglobin variants 2, 3, 4
  • Conditions such as dehydration hereditary stomatocytosis (DHS) can lead to shortened red blood cell lifespan, resulting in falsely low HbA1c values 2
  • Hemolytic anemia can also cause low HbA1c levels, as the shortened lifespan of red blood cells leads to a lower average glucose exposure 3
  • Transfusion-dependent thalassemia patients may have falsely elevated HbA1c levels due to the presence of minor Hb species and red cell transfusions 4

Relationship Between HbA1c and Blood Glucose Levels

  • HbA1c levels do not always accurately reflect blood glucose levels, as they can be influenced by various factors such as age, ethnicity, and renal disease 5
  • Studies have shown that HbA1c levels can be higher or lower than expected based on mean blood glucose levels in some individuals 5, 6
  • Fasting plasma glucose (FPG) and insulin secretion have been shown to be associated with HbA1c levels in the normal and pre-diabetic range 6

Limitations of HbA1c as a Diagnostic Tool

  • HbA1c has limitations as a diagnostic tool, particularly in individuals with certain medical conditions or those who have undergone recent blood transfusions 5, 3, 4
  • Alternative indices such as fructosamine levels, glycated albumin, and continuous glucose monitoring may be more accurate in certain situations 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

HbA1C - overall glycemia marker and hemolytic anemia indicator.

Medicinski glasnik : official publication of the Medical Association of Zenica-Doboj Canton, Bosnia and Herzegovina, 2012

Research

Beyond HbA1c.

Journal of diabetes, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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