Glucose Variability: Timing, Risk Analysis, and Relationship to Hypoglycemia in Diabetes

Glucose control, glucose variability (GV), and risk for hypoglycemia are intimately related, and it is now evident that GV is important in both the physiology and pathophysiology of diabetes. However, its quantitative assessment is complex because blood glucose (BG) fluctuations are characterized by both amplitude and timing. Additional numerical complications arise from the asymmetry of the BG scale. In this Perspective, we focus on the acute manifestations of GV, particularly on hypoglycemia, and review measures assessing the amplitude of GV from routine self-monitored BG data, as well as its timing from continuous glucose monitoring (CGM) data. With availability of CGM, the latter is not only possible but also a requirement-we can now assess rapid glucose fluctuations in real time and relate their speed and magnitude to clinically relevant outcomes. Our primary message is that diabetes control is all about optimization and balance between two key markers-frequency of hypoglycemia and HbA(1c) reflecting average BG and primarily driven by the extent of hyperglycemia. GV is a primary barrier to this optimization, including to automated technologies such as the "artificial pancreas." Thus, it is time to standardize GV measurement and thereby streamline the assessment of its two most important components-amplitude and timing.