Identification of the correlation between HbA1c and diabetic complications has yielded one of the most clinically useful biomarkers. HbA1c has revolutionised the diagnosis and monitoring of diabetes mellitus. However, with widespread adoption of HbA1c has come increasing recognition that non-glycaemic variables can also affect HbA1c, with varying clinical significance. Furthermore, the identification of a discrepancy between predicted and measured HbA1c in some individuals, the so-called ‘glycation gap’, may be clinically significant. We aimed to review the current body of evidence relating to non-glycaemic variables to quantify any significance and provide subsequent suggestions. A PubMed-based literature search was performed, using a variety of search terms, to retrieve articles detailing the non-glycaemic variables suggested to affect HbA1c. Articles were reviewed to assess the relevance of any findings in clinical practice and where possible guidance is given. A range of non-glycaemic variables have statistically significant effects on HbA1c. While the clinical implications are generally irrelevant, a small number of non-glycaemic variables do have clinically significant effects and alternative biomarkers should be considered instead of, or in addition to, HbA1c. There are a small number of non-glycaemic variables which have a clinically significant effect on HbA1c, However, the vast majority of non-glycaemic variables have no clinical relevance. While clinicians should have an awareness of those non-glycaemic variables with clinical significance, in the vast majority of clinical scenarios HbA1c should continue to be used with confidence.

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