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HbA1c: a review of non-glycaemic variables
  1. Leon Campbell1,
  2. Tessa Pepper1,
  3. Kate Shipman2
  1. 1 Department of Medicine, Western Sussex Hospitals NHS Foundation Trust, Worthing, UK
  2. 2 Department of Chemical Pathology, Western Sussex Hospitals NHS Foundation Trust, Worthing, England
  1. Correspondence to Dr Leon Campbell, Department of Elderly Medicine, St. Richard’s Hospital, Chichester PO19 6SE, England; leon.campbell{at}


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.

  • diabetes
  • diagnosis
  • pregnancy
  • biochemistry
  • analytical methods

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  • Handling editor Tahir S Pillay.

  • Contributors KS developed the plan for the article with the ACP chemical pathology committee. All authors made substantial contributions to the acquisition, analysis and interpretation of data for the work and both produced drafts and revised the work critically for important intellectual content. All authors provided final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.