Severe iron deficiency anemia can affect HbA1C results, making them unreliable for glycemic control
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD.
Glycated hemoglobin (HbA1c) at a level of 6.5 % is a cut-off for diagnosing diabetes, when the test has been performed in a laboratory using methods certified by National Glycohemoglobin Standardization Program (NGSP) certified and standardized to the Diabetes Control and Complications Trial (DCCT) assays(1) (Refer Table 1). Chronic vascular complications of diabetes, including atherosclerosis, cardiovascular disease, neuropathy, retinopathy, and nephropathy, are strongly associated with mismanaged glycemic control(2). However, inappropriately high HbA1c are seen in iron deficiency anemia and decreased after treatment with iron supplements(3). It is well-documented that iron deficiency anemia can lead to falsely elevated HbA1c levels, which subsequently decrease following iron supplementation(4). Therefore, a concurrent complete hemogram is essential to validate the reliability of glycemic assessment. To ensure clinical accuracy, AGD Biomedicals PVT LTD offers a fifth-generation diagnostic kit for HbA1c determination, fully compliant with NGSP standards(7) (Refer Case study).
Q1. What is glycated hemoglobin?
ANS(7): On exposure to blood glucose, hemoglobin gets non-enzymatically glycated at different sites in the molecule. HbA1c is formed when glucose gets added on to the N-terminal valine residue of the beta chain of hemoglobin. Since, the glycation process is irreversible, HbA1c levels serve as a reliable biomarker for the average glucose concentration to which erythrocytes were exposed during their circulating lifespan—averaging approximately 110–120 days. Consequently, HbA1c provides a clinical index of glycemic control over the preceding 8 to 12 weeks.
Q2. What is clinical signification of HbA1C test?
ANS: HbA1C test is recommended for the definitive diagnosis of prediabetes and diabetes mellitus, as well as for longitudinal monitoring of glycemic control(2). Refer Table 1.
CASE STUDY
A 42-year-old female presented to the local health center reporting generalized weakness, fatigue, palpitations, exertional dyspnea, and chest pain. Her history indicated no diabetes. Her clinical laboratory reports were as follows:
COMPLETE HEMOGRAM
| TEST | RESULT | REFERENCE RANGE |
| Hemoglobin | 7.6 g/dl | 13–18 g/dl |
| Total erythrocyte count | 3.45 X 1012 /l | 5.0 ± 0.5 X 1012 /l |
| Total leukocyte count | 8.3 X 109/l | 7.0 ± 3.0 X 109/l |
| Differential leukocyte count: | ||
| Neutrophils | 70% | 40–75% |
| Lymphocytes | 37% | 20–45 % |
| Eosinophils | 2% | 1–4 % |
| Monocytes | 1% | 2–8 % |
| PCV | 26% | 36–48% |
| MCV | 60 fL | 82–92 fL |
| MCH | 21 pg | 27–32 pg |
| MCHC | 30% | 32–36 % |
| RDW- CV | 21 | 12–14 |
| Platelet count | 180 X 109/l | 150–400 X 109/l |
| Metzer Index (MI) | 17.39 | < 13 |
STAINED BLOOD SMEAR EXAMINATION OBSERVATIONS:
Presence of significant microcytes, anisocytes and poikilocytes.
Hypochromia: +++
Microcytosis: ++++.
NOTE(7)
(A) The patient was suffering from microcytic hypochromic anemia related to Iron Deficiency Anemia (IDA) on the basis of the following CBC parameters: MI >13, very low Hb, PCV, MCV, MCH, MCHC, and high RDW-CV. To verify the diagnosis, it was advised to perform further tests such as serum total iron, TIBC, and ferritin.
THE REPORTS OF THE ADDITIONAL TESTS WERE AS FOLLOWS:
| TEST | RESULT | REFERENCE RANGE |
| Serum total iron | 48 µg/ l | 60-150 µg/ l |
| Serum Total Iron Binding Capacity (TIBC) | 440 µg/ l | 270-380 µg/ l |
| Serum ferritin | 4.5 µg/ l | 10-120 µg/ l |
DIAGNOSIS
Iron Deficiency Anemia (IDA)
| TEST | RESULT | REFERENCE RANGE |
| Blood glucose (Fasting) | 105 mg/dl | 70 – 110 mg/dl |
| Blood glucose (random) | 136 mg/dl | 70 – 110 mg/dl |
| HbA1C | 8.3% |
EVALUATION HbA1C report
Based on the patient’s case history and recorded blood glucose levels, there is no indication of diabetes. However, HbA1C value indicates poor glycemic control and average Blood glucose about 183 mg/dl (Refer Table 1). Her HbA1 level was expected < 7.0.
From these reports HbA1C value of this patient suffering from Iron Deficiency Anemia appears to be high.
Q3. Why might patients with iron-deficiency anemia exhibit falsely elevated HbA1C values?
ANS(6) : Malondialdehyde (MDA) levels are elevated in patients with iron deficiency anemia, leading to an increase in hemoglobin glycation. Conditions that affect erythrocyte turnover such as severe iron deficiency, hemolysis, blood loss and hemoglobin variants must be considered, particularly when the HbA1c result does not correlate with the patient’s clinical condition.
Q4. What is the underlying reason for elevated MDA levels observed in individuals with iron deficiency anemia?
ANS(6): Malondialdehyde (MDA) is a highly reactive three-carbon organic compound that serves as a primary marker for oxidative stress in biological systems. Sufficient iron in blood circulation is required to prevent oxidative stress. Iron deficiency leads to an increased level of oxidative stress. MDA is the main end-product of lipid peroxidation, where reactive oxygen species (ROS) break down polyunsaturated fatty acids (PUFAs) in cell membranes. Because of its high reactivity, MDA can covalently bond with proteins and DNA, forming adducts that disrupt normal cellular functions.
TABLE 1
| HbA1c (%) | Estimated Average Blood Glucose (mg/dl) |
| 5 | 97 |
| 6 | 126 |
| 7 | 154 |
| 8 | 183 |
| 9 | 212 |
| 10 | 240 |
Normal: Below 5.7% (Approx. <117 mg/dL)
Prediabetes: 5.7% to 6.4% (Approx. 117–137 mg/dL)
Diabetes: 6.5% or higher (Approx. >140 mg/dL)
References
(1) Sultanpur CM, Deepa K, Kumar SV. Comprehensive review on HbA1c in diagnosis of diabetes mellitus. Int J Pharm Sci Rev Res. 2010;3(2):119–22.
(2) American Diabetes Association. Standards of medical care in diabetes, 2013. Diabetes Care. 2013;36(1):S11–66.
(3) A Case of Inappropriately High Glycated Hemoglobin. Moushumi Lodh, Rajarshi ukhopadhyay, Balwant Kumar. Ind J Clin Biochem (Apr-June 2015) 30(2):234–237.
(4) Christy AL, Manjrekar PA, Babu RP, Hegde A. Influence of iron deficiency anaemia on haemoglobin A1C levels in diabetic individuals with controlled plasma glucose levels. Iran Biomed J. 2014;18(2):88.
(5) Kalasker V, Kodliwadmath MV, Bhat H. Effect of iron deficiency anaemia on glycosylated haemoglobin levels in non diabetic Indian adults. Int J Med Hlth Sci. 2014;3(1):40-43.
(6) Selvaraj N, Bobby Z, Sathiyapriya V. Effect of lipid peroxides and antioxidants on glycation of hemoglobin: an in vitro study on human erythrocytes. Clin Chim Acta. 2006;366:190–5.
(7) Godkar PB, Godkar DP. Textbook of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
