The major findings of the present study using the FGM were the following: 1) AIQR correlated negatively with TIR, 2) the longer the time blood glucose level is between 70 and 180 mg/dL, the smaller the variation range in AGP, 3) AIQR correlated positively with SD, CV, and MODD, and 4) Lack of relationship between AIQR and hypoglycemia.
Our study also established the AIQR cutoff values for achieving the TIR target values. AGP is an excellent tool that clearly and visually presents the trends in blood glucose variability for the individual patient9; our study showed that AIQR is a valuable index for use in AGP.
Our data showed that AIQR correlates negatively with TIR, and that the longer the time blood glucose is maintained within the range of 70 to 180 mg/dL, the smaller the variation range in AGP. TIR refers to the percent time during the 24-hour period when blood glucose is within the range of 70–180 mg/dL. TIR provides a more complete picture of blood glucose than HbA1c, and hence makes it possible to offer personalized treatment options10. Similar to HbA1c, TIR time is reported to correlate strongly with the risk of retinopathy and/or onset of microalbuminuria2. Other studies found that TIR is independent of HbA1c and that it is associated with cardiovascular autonomic neuropathy11. Furthermore, TIR correlates strongly with HbA1c12, and was recently recommended by the American Diabetes Association (ADA) for use along with HbA1c for targeted blood glucose control.
IQR is in the 25-75th percentile range on the AGP, and is an excellent visual indicator of glucose variability13, 14; although there is no reported relationship between IQR and standardized CGM metrics. To our knowledge, our study is the first to define the AIQR-TIR relationship. Importantly, setting the cutoff values for AIQR makes it easier to evaluate treatment goals especially achieving the TIR targets. Following ADA’s target of TIR > 70% in T2DM patients, we established the AIQR cutoff values of 28.3 mg/dL for TIR > 70% and 22.9 mg/dL for a stricter adherence to TIR > 90%. These indexes are useful markers to use when setting target treatment values using the AGP.
The IQR has also been discussed as a marker of interday variations15. Another strong aspect of our study was the strong correlation between AIQR and the SD and CV (which are markers of intraday variations), in addition to the correlation between AIQR and MODD (which is a marker of interday variation). In this regard, Monnier et al.16 proposed the use of indexes that can evaluate blood glucose variability in addition to chronic hyperglycemia and hypoglycemia, as a strategy for monitoring blood glucose to inhibit progression of cardiovascular disorders. The results of the present study suggest that IQR is useful index for evaluation of intra- and interday variations in blood glucose levels. In practical clinical settings from hereon, a large IQR will require analysis of the factors behind interday variations, as well as necessitate evaluation of the factors responsible for intraday variations, including, for example, postprandial glucose and low blood glucose levels.
Our analysis showed the lack of any association between AIQR and presence of hypoglycemia, and that low blood glucose is associated with AG and LBGI. These results suggest that AIQR is not suitable for use to predict the extent of hypoglycemia; and thus, we advise instead to visually evaluate each case when assessing low blood glucose in AGP. It is noteworthy that a number of investigators found close associations between low blood glucose and certain markers, such as AG and LBGI17, 18, similar to our findings. Therefore, AG, CV, LBGI and other CGM metrics can also be used with other indexes to evaluate objectively the risk of hypoglycemia in clinical settings.
There were two limitations in this study. The first is we did not record glucose density of ≥ 500 mg/dL based on the use of FGM, and accordingly, or study did not include patients with poor blood glucose control. This is an important limitation to mention here because the results for such patients may be different from those obtained in the present study. The second limitation is that this research work was a cross-sectional study conducted at two facilities with only a relatively small number of patients. We need to proactively continue with our research on a larger scale in order to substantiate the results of this study.