Response to 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 are grateful to Schindhelm et al. (1) for their interest in our article. We measured HbA_1c during follow-up of a birth cohort in the hope of substituting it for an oral glucose tolerance test. We found a discrepancy between the results of the oral glucose tolerance test (World Health Organization, 1999) and HbA_1c (American Diabetes Association, 2009): A large number of individuals were classified as having “prediabetes” by HbA_1c when considered normal glucose tolerant by oral glucose tolerance test (2). This prompted us to investigate possible causes of this discrepancy. We found that a number of hematological parameters (lower hemoglobin concentration, lower mean corpuscular volume, lower mean corpuscular hemoglobin, and higher red cell distribution width) predicted higher HbA_1c. These hematological parameters were indicative of iron deficiency, so we measured serum ferritin concentrations. We found that lower ferritin concentrations also predicted higher HbA_1c, supporting an association with iron deficiency. We did not find an association of HbA_1c with another nutritional problem, i.e., vitamin B12 deficiency, which is quite common in this population. We searched the literature and found supportive data that HbA_1c is elevated in iron deficiency. We admit that our interpretation of previous studies (3,4) about prolonged erythrocyte survival in iron deficiency was not accurate.

Unfortunately, we do not have reticulocyte measurements in our study, nor do we have the expertise to perform the measurements that Schindhelm et al. suggest. We agree that the explanation for elevated HbA_1c concentrations in iron deficiency could be more complex than those suggested in the past. We would appreciate if Schindhelm et al. could transfer the technology to us to make relevant measurements.

Irrespective of the possible explanation, the basic findings and conclusions of our study remain valid; i.e., young nondiabetic individuals with iron deficiency have an inappropriately high HbA_1c concentration. In a subsequent study of 232 rural adolescents, we found a similar pattern: those with hemoglobin concentrations below 12 g% (n = 116) were 45% prediabetic by HbA_1c criteria compared with 15.5% in those with hemoglobin concentrations above 12 g% (P < 0.001) despite normal glucose tolerance. Use of HbA_1c to diagnose prediabetes and diabetes in nutritionally compromised populations might produce misleading estimates of prevalence.