The clinical importance of measuring glycaemic variability: Utilising new metrics to optimise glycaemic control

Abstract

With the widespread use of continuous glucose monitoring (CGM), glycaemic variability (GV) is a glucose metric that has been gaining increasing attention. However, unlike other glucose metrics that are easily defined and have clear targets, GV has a large number of different measures given the complexity involved in assessment. While variabilities in HbA1c, fasting and postprandial glucose have been incorporated under the GV banner, short-term variability in glucose, within day and between days, is more in keeping with the correct definition of GV. This review is focused on short-term GV, as assessed by CGM data, although studies calculating GV from capillary glucose testing are also mentioned as appropriate. The different measures of GV are addressed, and their potential role in microvascular and macrovascular complications, as well as patient-related outcomes, discussed. It should be noted that the independent role of GV in vascular pathology is not always clear, given the inconsistent findings in different populations and the close association between GV and hypoglycaemia, itself an established risk factor for adverse outcomes. Therefore, this review attempts, where possible, to disentangle the contribution of GV to diabetes complications from other glycaemic parameters, particularly hypoglycaemia. Evidence to date strongly suggests an independent role for GV in vascular pathology but future large-scale outcome studies are required to fully understand the exact contribution of this metric to vascular complications. This can be followed by setting appropriate GV measures and targets in different diabetes subgroups, in order to optimise glycaemic management and limit the risk of complications.

Keywords: continuous glucose monitoring; glycaemic variability; hypoglycaemia; macrovascular complications; microvascular complications; patient‐related outcome measures; type 1 diabetes; type 2 diabetes.

FIGURE 1

The five main dimensions of glycaemic variability (GV). These different dimensions explain that existence of a large number of GV metrics.

FIGURE 2

Potential mechanisms of glycaemic variability (GV)–induced vascular pathology. GV is associated with endothelial dysfunction, increased reactive oxygen species (ROS) production and epigenetic changes, creating an inflammatory and prothrombotic environment, thus contributing to vascular pathology. While current evidence strongly suggests an independent role for GV in vascular complications of diabetes, the interaction of GV metrics with both hypoglycaemia and hyperglycaemia, and even insulin resistance, can make disentangling the exact role of each problematic. Overall, it is likely that GV potentiates the adverse effects of metabolic abnormalities in diabetes, although the evidence for this remains largely circumstantial and more work in this area is required.

FIGURE 3

Refining the future use of glycaemic variability (GV). A number of steps should be taken to reduce the large number of GV markers in current use coupled with conducting appropriate studies to understand the independent, or additive/synergistic, role of GV in diabetes complications. This includes renaming GV markers that are not derived from frequent daily glucose measures, such as HbA1c and fasting glucose changes over a period of time. Findings from research studies should be translated into routine clinical use of different GV markers together with setting appropriate targets in the different subpopulations of people with diabetes.