Analytical Performance of the FreeStyle Libre 2 Glucose Sensor in Healthy Male Adults

Abstract

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.

Keywords: CGM; MARD; glycemic control; oral glucose tolerance test; sensor accuracy.

Figure 1

Graphical overview of the study design: On day 1 (initial assessment), participants were instructed and CGM sensors were applied onto their attachment site. On day 4, after a carbohydrate-rich nutrition for the last three days and an 8–12 h fast, they were asked to ingest a glucose drink to start the OGTT. Simultaneous ISFG and CPG were taken at T0, T30, T60, T90, and T120. Abbreviations: CGM = continuous glucose measurement, ISFG = interstitial fluid glucose, CPG = capillary glucose, OGTT = oral glucose tolerance test, T0 = fasting baseline, T30, T60, T90, T120 = 30, 60, 90, 120 min post OGTT.

Figure 2

Fulfillment of accuracy criteria: Dots (N = 149) depict matched glucose pairs meeting the ISO 15197:2013 criteria, and triangles (N = 71) lie outside the boundaries of the ISO 15197:2013. Note: Boundaries are as follows: If reference glucose CPG is <100 mg/dL, ISFG must fall within ±15 mg/dL of reference glucose or within ±15% when the reference glucose values are greater than 100 mg/dL. Approximately 95% of matched glucose pairs shall fall within these boundaries to satisfy the ISO 15197:2013 criteria. In this case, 67.7% met the necessary requirements. Abbreviations: CPG = capillary blood glucose, ISFG = interstitial fluid glucose.

Figure 3

Consensus Error Grid analysis of the Freestyle Libre 2 Sensor (220 matched glucose pairs). ISFG measurements (interstitial fluid glucose; serves as test glucose concentration) were plotted against CPG measurements (capillary glucose; serves as reference glucose concentration). According to ISO 15197:2013, 99% of matched glucose pairs should fall in zones A and B. Dashed lines depict the boundaries of the zones, implying different degrees of risk for clinical decision-making. Red dots are values falling into zone A (no effect on clinical action), whereas blue dots are values falling into zone B (altered clinical action with little or no effect on clinical outcomes). Zone C: altered clinical action that is likely to affect clinical outcomes. Zone D: altered clinical action that could have significant medical risks. Zone E: altered clinical action that could have dangerous consequences.

Figure 4

Bland–Altman plot of sensor and capillary glucose levels. The solid red line represents the mean difference between the sensor and capillary glucose values (11.1 mg/dL); the dashed lines indicate 1.96 × SD of the difference. Abbreviations: CPG = capillary blood glucose, ISFG = interstitial fluid glucose.

Figure 5

Glucose dynamics of ISFG and CPG in the OGTT over time at discrete timepoints. Paired t-test revealed significant differences (p < 0.001) at each timepoint with ISFG systematically under-reporting the CPG measurements. Abbreviations: ISFG = interstitial fluid glucose, CPG = capillary blood glucose, T0 = fasting baseline, T30, 60, 90, 120 = 30, 60, 90, 120 min post oral glucose tolerance test.