Abstract
BACKGROUND: We aimed to identify the normal range of glucose rates of change (RoC) observed in health and assess whether existing metrics of temporal glycemic variability (GV-timing), such as mean absolute glucose change (MAG) and continuous overlapping net glycemic action (CONGA), are predictive of abnormally rapid RoC in type 1 diabetes (T1D). METHODS: We identified the normal range of RoC over one-hour intervals from continuous glucose monitoring (CGM) data of healthy individuals. Rapidly rising glucose was defined as RoC values above percentiles 99% (level 1, L1) or 99.9% (level 2, L2), and rapidly falling glucose as below 1% (L1) or 0.1% (L2). The percentage of time these thresholds are exceeded in a given individual is referred to as time in fluctuation (TIF). In a separate CGM dataset of 736 T1D individuals, we calculated TIF-L1 and TIF-L2, and compared them against corresponding values of MAG and CONGA. RESULTS: The extremum percentiles of RoC observed in health are 0.1%: -80 mg/dL/h, 1%: -50 mg/dL, 99%: +56 mg/dL/h, and 99.9%: +89 mg/dL/h. The T1D individuals spend significantly more TIF at rates exceeding these thresholds (TIF-L1: median, 16.7% [interquartile range, 12.7-21.5], TIF-L2: 5.0% [3.1-7.8]) than healthy individuals (TIF-L1: 1.4% [0.6-2.8], TIF-L2: 0.0% [0.0-0.2]). Both MAG and CONGA are highly correlated with TIF-L1 and TIF-L2 (r > .95 in each pairwise comparison). CONCLUSIONS: Individuals with T1D spend significant time with glucose RoC exceeding those observed in health. Existing GV-timing metrics are strongly correlated with time with abnormal RoC. Incorporation of a GV-timing metric in clinical practice is recommended.