Comment on: Hardikar et al. Spuriously high prevalence of prediabetes diagnosed by HbA(1c) in young indians partly explained by hematological factors and iron deficiency anemia. Diabetes Care 2012;35:797–802.

We read with great interest the article by Hardikar et al. (1). In their epidemiological study in nondiabetic subjects, the authors observed an inverse association between HbA1c and hemoglobin levels, mean cell volume, and mean cell hemoglobin. In the multivariate models, laboratory parameters indicating iron deficiency anemia were negatively associated with HbA1c. On the basis of their study, Hardikar et al. support the notion that iron deficiency contributes to an increased erythrocyte survival and a falsely elevated HbA1c in subjects with similar degrees of glycemia. These data seem to be in contradiction with experimental studies showing that anemia in patients with iron deficiency is not only the result of an ineffective erythropoiesis but is also explained by a decreased erythrocyte life span (2,3) due to an increased programmed cell death (eryptosis) with enhanced removal of erythrocytes from the circulation (4). In the light of these experimental studies, it would have been more informative if data on erythrocyte production, as reflected by the reticulocyte count, and the degree of hemoglobinization of erythrocytes and reticulocytes were provided (5).

The higher HbA1c results in subjects with iron deficiency anemia are more likely due to a relative survival of previously formed noniron-deficient erythrocytes with a relatively higher level of glycation and a decreased survival of younger erythrocytes with a lower degree of glycation. These assumptions should be investigated in longitudinal studies assessing the rate of glycation in relation to erythrocyte life span and survival.