Factors that affect interpretation of HbA1c Results.

[Argirios Argiriou]

Factors that Interfere with HbA1c Measurement:

Genetic variants (e.g. HbS trait, HbC trait), elevated fetal hemoglobin (HbF) and chemically modified derivatives of hemoglobin (e.g. carbamylated Hb in patients with renal failure) can affect the accuracy of HbA1c measurements. The effects vary depending on the specific Hb variant or derivative and the specific HbA1c method. Table 1 contains information for most of the commonly used current HbA1c methods for the four most common Hb variants, elevated HbF and carbamylated Hb. Interferences from less common Hb variants and derivatives are discussed in Bry, et al [1]. All entries in Table 1 are based on published information. In addition, if a product insert indicates clearly that there is inference from a particular factor, then the interference is entered as “yes” and the product insert is cited. When selecting an assay method, laboratories should take into consideration characteristics of the patient population served, (e.g. high prevalence of hemoglobinopathies or renal failure).

Factors that affect interpretation of HbA1c Results:

Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (e.g., recovery from acute blood loss, hemolytic anemia) will falsely lower HbA1c test results regardless of the assay method used [2]. HbA1c results from patients with HbSS, HbCC, and HbSC must be interpreted with caution given the pathological processes, including anemia, increased red cell turnover, and transfusion requirements, that adversely impact HbA1c as a marker of long-term glycemic control. Alternative forms of testing such as glycated serum protein or glycated albumin should be considered for these patients.
Iron deficiency anemia, a major public health problem in developing countries, is associated with higher HbA1c and higher fructosamine [3]. Consistent with these observations, iron replacement therapy lowers both HbA1c and fructosamine concentrations in diabetic and non-diabetic individuals [3-5]. HbA1c , but not glycated albumin, is increased in late pregnancy in nondiabetic individuals owing to iron deficiency [6]. Insight into the mechanism was recently obtained by the observation that malondialdehyde, which is increased in patients with iron deficiency anemia [3], enhances the glycation of hemoglobin [7]. Alternative measures of glycemic assessment (e.g., glucose monitoring) must be used in the presence of significant iron deficiency anemia, at least until the iron deficiency has been successfully treated.
Chronic renal failure develops in many diabetic patients. The role of glycemic control and the value of HbA1c in diabetic subjects with renal disease are controversial. While interference from carbamylated Hb can be evaluated, the role of renal anemia, erythropoietin intake, and other factors in chronic renal failure is more difficult to evaluate. Recent reports suggest HbA1c underestimates glycemic control in diabetic patients on dialysis and that glycated albumin is a more robust indicator of glycemic control [8-11]. Further studies are needed to clarify the role of HbA1c in diabetic patients with chronic renal failure.

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