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How Anemia Affects A1c

Feb 9, 2021
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Lawand Kamal, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences

A new study shows that resolving iron deficiency and or vitamin B12 deficiency anemia may affect A1c levels. 

One of the most common tools used to screen for and evaluate a person’s control of diabetes is a glycated hemoglobin (A1c) test. An A1c test is advantageous because it reflects a patient’s average blood glucose levels over three months and is likely less affected by temporary changes in diet and exercise. However, many conditions affect a patient’s red blood cells (RBCs) and therefore a patient’s A1c test results. A previous study conducted by Brooks et al. showed that iron deficiency anemia might alter the glycation rate of hemoglobin and cause elevations in A1c levels regardless of glycemia in patients without diabetes. Multiple other studies conducted by Tarim et al. and Kim et al. have shown that the resolution of iron deficiency anemia led to statistically significant alterations in A1c levels in both patients living with type 1 diabetes (T1D) and patients living without diabetes, respectively. Current studies have focused on the effects of iron deficiency on A1c levels but have not fully explored vitamin B12 deficiencies. Understanding the impact that iron and vitamin B12 deficiencies have on A1c test results may change how they are interpreted. 

 

A study by Pendela et al. was performed to evaluate the effects of iron deficiency, vitamin B12 deficiency, and dual deficiency anemia on A1c levels and to understand the impact treatment of anemia may have on patients’ diabetes status. A total of 70 patients between the ages of 18 to 70 had iron and or vitamin B12 deficiency anemia and were evaluated at the end of the study. Patients living with diabetes, other forms of anemia, and significant organ dysfunction, among other hemoglobinopathies, were excluded from the study. An initial A1c was measured for all patients at the start of the study. Patients then had their anemia treated according to the type of nutrition deficiency with either oral iron or intravenous cobalamin therapy. A1c levels were measured again after three months and were compared for significance against initial A1c values. Patients were divided into either subgroup 1 (decrease in A1c after treatment) or subgroup 2 (increase in A1c after treatment) and based on their various nutritional deficiencies. A paired t-test was used to analyze the change in average A1c in each of the subgroups. 

The mean change in A1c for patients in subgroup 1 (decrease in A1c after treatment) was 0.65% [95% CI 0.5, 0.744], 0.56% [0.45, 0.68], and 0.68% [0.44, 0.91] for iron deficiency, vitamin B12 deficiency, and dual deficiency anemias, respectively. All results were statistically significant where p<0.01. 

The mean change in A1c for patients in subgroup 2 (increase in A1c after treatment) was –0.68% [95% CI –0.74, –0.44], –0.64% [–0.83, –0.57], and –0.63% [–1.01, –0.25] for iron deficiency, vitamin B12 deficiency, and dual deficiency anemias, respectively. All results were statistically significant (p<0.01 for iron and vitamin B12 deficiencies and p=0.019 for double deficiency). A total of 27 patients were considered as living with prediabetes without considering their anemia status, and ten patients met the criteria for prediabetes after the treatment of their anemia. 

Based on the study results by Pendela et al., treatment of iron deficiency and or vitamin B12 deficiency anemia can significantly elevate or reduce a patients A1c level. However, there appears to be no trend or explanation provided by the authors for why some patients had a decrease in their A1c and why others had an increase in their A1c after treatment. A significant limitation in this study was that subgroups were not powered, and no analysis was conducted to tease out differences between groups and the observed results. This study’s further limitations were that a control group was not utilized to eliminate confounding factors and that the study population was relatively small (<10 patients in three of the six total subgroups). There are mixed results among other studies evaluating the effects of iron deficiency anemia on whether treatment decreases or increases A1c levels.  Further and larger-scale studies are needed to investigate reasons as to why variations in A1c occur with the treatment of iron deficiency anemia and or vitamin B12 deficiency anemia.  

Practice Pearls: 

  • Treatment of iron and or vitamin B12 deficiency anemia can significantly alter a persons A1c level. 
  • Iron and vitamin B12 levels should be considered before using an A1c test as a diagnostic tool for diabetes screening. 
  • Reasons for A1c decreases or increases after treatment of iron and or vitamin B12 deficiency anemia are currently unclear. 

 

Brooks, A P et al. Iron deficiency and glycosylated hemoglobin A. Lancet (London, England) vol. 2,8186 (1980): 141 

Tarim, O et al. Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus. Pediatrics international: official journal of the Japan Pediatric Society vol. 41,4 (1999): 357-62. doi:10.1046/j.1442-200x.1999.01083.x. 

Kim, Catherine et al. Association between iron deficiency and A1C Levels among adults without diabetes in the National Health and Nutrition Examination Survey, 1999-2006. Diabetes care vol. 33,4 (2010): 780-5. doi:10.2337/dc09-0836 

Pendela, Venkata Satish, et al. 1455-P: Effect of Treatment of Anemia on HbA1c Levels. Diabetes, vol. 69, no. Supplement 1, 2020, doi:10.2337/db20-1455-p. 

 

Lawand Kamal, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences