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  • Review Article
  • Published:

Metrics for glycaemic control — from HbA1c to continuous glucose monitoring

Nature Reviews Endocrinology volume 13, pages 425–436 (2017)Cite this article

Subjects

Key Points

  • Fluctuations in blood levels of glucose in diabetes mellitus manifest on several clinically relevant timescales, from gradual months-long changes in average glycaemia (reflected by levels of HbA1c) to fast transitions captured by continuous glucose monitoring

  • As intensive treatment of diabetes mellitus characteristically results in an increased incidence of hypoglycaemia, safe and clinically meaningful lowering of HbA1c levels can only be achieved if accompanied by a reduction in glucose variability

  • Although established for decades, HbA1c measures average blood glucose indirectly and has certain limitations; thus, along with HbA1c, glucose variability is increasingly regarded as a primary marker of glycaemic control

  • Various metrics of glucose variability exist that use self-monitoring data to assess the amplitude of blood glucose excursions or continuous monitoring to predict hypoglycaemia and hyperglycaemia and design artificial-pancreas algorithms

  • Certain classes of medication (for example, glucagon-like peptide 1 receptor agonists and dipeptidyl peptidase 4 inhibitors) have a pronounced variability-reducing effect; thus, glucose variability analyses will help to better evaluate their use in the treatment of diabetes mellitus

  • As technology exists for the direct observation of fluctuations in blood glucose, assessment of the efficacy of diabetes mellitus treatment can move beyond the HbA1c assay as the sole marker of glycaemic control

Abstract

As intensive treatment to lower levels of HbA1c characteristically results in an increased risk of hypoglycaemia, patients with diabetes mellitus face a life-long optimization problem to reduce average levels of glycaemia and postprandial hyperglycaemia while simultaneously avoiding hypoglycaemia. This optimization can only be achieved in the context of lowering glucose variability. In this Review, I discuss topics that are related to the assessment, quantification and optimal control of glucose fluctuations in diabetes mellitus. I focus on markers of average glycaemia and the utility and/or shortcomings of HbA1c as a 'gold-standard' metric of glycaemic control; the notion that glucose variability is characterized by two principal dimensions, amplitude and time; measures of glucose variability that are based on either self-monitoring of blood glucose data or continuous glucose monitoring (CGM); and the control of average glycaemia and glucose variability through the use of pharmacological agents or closed-loop control systems commonly referred to as the 'artificial pancreas'. I conclude that HbA1c and the various available metrics of glucose variability reflect the management of diabetes mellitus on different timescales, ranging from months (for HbA1c) to minutes (for CGM). Comprehensive assessment of the dynamics of glycaemic fluctuations is therefore crucial for providing accurate and complete information to the patient, physician, automated decision-support or artificial-pancreas system.

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Figure 1: Self-monitored blood levels of glucose recorded over 60 days.
Figure 2: Risk analysis of blood glucose data.
Figure 3: Effectiveness of overnight closed-loop control in reducing glucose variability.

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Acknowledgements

The author's research is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant RO1 DK051562).

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Authors and Affiliations

  1. University of Virginia School of Medicine, 1215 Lee Street, Charlottesvile, 22908, Virginia, USA

    Boris P. Kovatchev

  2. The School of Engineering and Applied Sciences, University of Virginia, Thornton Hall, P.O. Box 400259, Charlottesville, 22904–4259, Virginia, USA

    Boris P. Kovatchev

  3. Center for Diabetes Technology, University of Virginia School of Medicine, Ivy Translational Research Building, 560 Ray C. Hunt Drive, Charlottesville, 22903–2981, Virginia, USA

    Boris P. Kovatchev

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Correspondence to Boris P. Kovatchev.

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Competing interests

The author has received research grants and personal fees from Dexcom and Sanofi-Aventis, research material support from Dexcom, Roche Diagnostics and Tandem Diabetes Care, holds intellectual property relevant to the subject of this Review (handled through the University of Virginia Licensing and Ventures Group) and is board member and a shareholder in TypeZero Technologies.

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Kovatchev, B. Metrics for glycaemic control — from HbA1c to continuous glucose monitoring. Nat Rev Endocrinol 13, 425–436 (2017). https://doi.org/10.1038/nrendo.2017.3

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