The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review

Aims/hypothesis The use of HbA(1c) for the diagnosis of diabetes is now widely advocated despite caveats to its use. Anaemia is cited as a major confounder to this use; however, the effect of erythrocyte indices and to what degree anaemia influences HbA(1c) levels is not known. Methods A systematic electronic database search of MEDLINE, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL) and the Cochrane Library was conducted for relevant articles published between January 1990 and May 2014. Included studies had at least one measurement of HbA(1c) and glucose, and a least one index of haematinic deficiency, involving non-pregnant adults, not known to have diabetes. Results A total of 12 articles from 544 were included. The majority of studies focused on iron deficiency anaemia (IDA) and, in general, demonstrated that the presence of iron deficiency with or without anaemia led to an increase in HbA(1c) values compared with controls, with no concomitant rise in glucose indices. Data on the effects of other indices of erythrocyte abnormalities on HbA(1c) are limited but show a possible decrease in HbA(1c) values with non-iron deficiency forms of anaemia. Conclusions/interpretation HbA(1c) is likely to be affected by iron deficiency and IDA with a spurious increase in HbA(1c) values; conversely, non-IDA may lead to a decreased HbA(1c) value. This may lead to confusion when diagnosing diabetes using HbA(1c). This review clearly identifies the need for more evidence, especially in identifying the types and degrees of anaemia likely to have significant impact on the reliability of HbA(1c).