Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control

Abstract

Glycosylated hemoglobin (HbA1c) has been the sole surrogate marker for assessing diabetic complications. However, consistently reported limitations of HbA1c are that it lacks detailed information on short-term glycemic control and can be easily interfered with by various clinical conditions such as anemia, pregnancy, or liver disease. Thus, HbA1c alone may not represent the real glycemic status of a patient. The advancement of continuous glucose monitoring (CGM) has enabled both patients and healthcare providers to monitor glucose trends for a whole single day, which is not possible with HbA1c. This has allowed for the development of core metrics such as time spent in time in range (TIR), hyperglycemia, or hypoglycemia, and glycemic variability. Among the 10 core metrics, TIR is reported to represent overall glycemic control better than HbA1c alone. Moreover, various evidence supports TIR as a predictive marker of diabetes complications as well as HbA1c, as the inverse relationship between HbA1c and TIR reveals. However, there are more complex relationships between HbA1c, TIR, and other CGM metrics. This article provides information about 10 core metrics with particular focus on TIR and the relationships between the CGM metrics for comprehensive understanding of glycemic status using CGM.

Keywords: Blood glucose; Blood glucose self-monitoring; Diabetes complications; Glycated hemoglobin A.

Fig. 1

(A) Even in patients with the same glycosylated hemoglobin (HbA1c) or mean glucose, exact glycemic control may vary. For example, some patients can have excellent glycemic control, spending the whole day with glucose levels between 70 and 180 mg/dL; on the other hand, some patients’ glucose levels may range from 50 to 250 mg/dL. (B) Self-monitoring blood glucose (SMBG) cannot fully capture actual glycemic fluctuation like continuous glucose monitoring (CGM) measuring interstitial glucose level every 5 to 15 minutes (96 to 288 measurements/day). TAR, time above range; TBR, time below range; TIR, time in range.

Fig. 2

The ambulatory glucose profiles. Adapted from Ambulatory Glucose Profile [13]. CGM, continuous glucose monitoring.

Fig. 3

(A) The inverse linear relationship between change in time in range (TIR) and change in glycosylated hemoglobin (HbA1c) differs by baseline HbA1c. A 10% increase in TIR only matches with a decrease of −0.4% of HbA1c in those with baseline HbA1c <7.0% but with a decrease of −1.0% in HbA1c in those with baseline HbA1c ≥8.0%. (B) The inverse linear relationship between TIR and mean glucose is preserved only in glucose values 120 to 200 mg/dL, and reversely falls when the glucose level decreases below 120 mg/dL. (C) The relationship between TIR and HbA1c differs by %CV. TIR was much lower in those with high %CV, even in those with the same HbA1c. Adapted from Beck et al. [22] and Rodbard [27], with permission from Mary Ann Liebert, Inc. CV, coefficient of variance.