Anaemia and haemoglobin A1c level: Is there a case for redefining reference ranges and therapeutic goals?

Background: Haemoglobin A1c (HbA1c) has been adopted by physicians as a surrogate for monitoring glycemic control. There exists concern that other factors beyond serum glucose concentration may affect glycation rates and by extrapolation HbA1c levels. Study Objectives: The study attempts to discern clinical differences in HbA1c levels in patients with anaemia compared to patients without anaemia, quantifying and showing the direction of such differences. Study Design: Using a convenient sampling method and a set of inclusion and exclusion criteria, it examined (retrospectively) patterns in [Hb] and HbA1c in non-diabetics with and without anaemia. Results: The study observed a statistically significant 0.4units (8%) difference in the mean HbA1c in anaemia vs. non-anaemic populations. Reference ranges of HbA1c for non-anaemic population and anaemia subtypes was computed. Computed ranges for anaemia group and its subgroups were significantly wider compared to non-anaemia population. Modest but statistically significant correction of anaemia did not result in significant changes in HbA1c. Discussion: i. The linear relationship between [Hb] and HbA1c holds true for anaemic and non-anaemia populations. ii. Non-diabetic, anaemic have a significantly lower mean HbA1c (5.3% vs. 5.7%), but a similar upper limit of reference range due to a higher variance. iii. The variance and proposed reference ranges for anaemia group and its subtypes was greater than in non-anaemia group, perhaps due to homogenization of clinically heterogeneous entities. iv. Modest correction anaemia did not cause significant change in HbAIc, perhaps the increase in [Hb] was too modest or persistence of correction was too short to be impactful. Conclusion: It makes the case for defining HbA1c reference ranges for each anaemia subtype, as well as utilizing other surrogates for monitoring glycemic control in populations with anaemia.