A Prospective Study on Continuous Glucose Monitoring in Glycogen Storage Disease Type Ia: Toward Glycemic Targets

Alessandro Rossi, Annieke Venema, Petra Haarsma, Lude Feldbrugge, Rob Burghard, David Rodriguez-Buritica, Giancarlo Parenti, Maaike H Oosterveer, Terry G J Derks, Alessandro Rossi, Annieke Venema, Petra Haarsma, Lude Feldbrugge, Rob Burghard, David Rodriguez-Buritica, Giancarlo Parenti, Maaike H Oosterveer, Terry G J Derks

Abstract

Context: Although previous research has shown the benefit of continuous glucose monitoring (CGM) for hepatic glycogen storage diseases (GSDs), current lack of prospectively collected CGM metrics and glycemic targets for CGM-derived outcomes in the hepatic GSD population limits its use.

Objective: To assess CGM metrics for glycemic variation and glycemic control in adult patients with GSDIa as compared to matched healthy volunteers.

Design: Prospective CGM data were collected during the ENGLUPRO GSDIa trial (NCT04311307) in which a Dexcom G6 device was used. Ten adult patients with GSDIa and 10 age-, sex- and body mass index-matched healthy volunteers were enrolled. Capillary blood glucose was concurrently measured during 2 standardized 2-hour time intervals. Descriptive [eg, glycemic variability (GV), time below range, time in range (TIR), time above range (TAR)] and advanced (ie, first- and second-order derivatives, Fourier analysis) CGM outcomes were calculated. For each descriptive CGM outcome measure, 95% CIs were computed in patients with GSDIa and healthy volunteers, respectively.

Results: CGM overestimation was higher under preprandial and level 1 hypoglycemia (ie, capillary glucose values ≥ 3.0 mmol/L and < 3.9 mmol/L) conditions. GV and TAR were higher while TIR was lower in patients with GSDIa compared to healthy volunteers (P < 0.05). Three patients with GSDIa showed descriptive CGM outcomes outside the calculated 95% CI in GSDIa patients. Advanced CGM analysis revealed a distinct pattern (ie, first- and second-order derivatives and glucose curve amplitude) in each of these 3 patients within the patients group.

Conclusions: This is the first study to prospectively compare CGM outcomes between adult patients with GSDIa and matched healthy volunteers. The generation of a set of CGM metrics will provide guidance in using and interpreting CGM data in GSDIa and will be useful for the definition of glycemic targets for CGM in patients with GSDIa. Future studies should investigate the prognostic value of CGM outcomes and their major determinants in patients with GSDIa.

Keywords: continuous glucose monitoring; diet; glycogen storage disease type Ia; management; monitoring; precision medicine.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Bland-Altman plots. Difference between continuous glucose monitoring (CGM) values and capillary blood glucose (CBG) measured by the Freestyle Freedom Lite (Abbott, Chicago, IL, USA) device, expressed as absolute (A, C, E, G, I, and K, in mmol/L) and relative (B, D, F, H, J, and L, in %) values. Y-axis shows the absolute (A, C, E, G, I, and K) or relative (B, D, F, H, J, and L) difference between CBG and CGM values at each study time point. X-axis shows the average glucose value at each study time point. Bias (black thick line), 95% CI (grey thin lines), and regression line (diagonal line, various colors) are shown. (A and B) Data were collected under preprandial/fasted [n = 200 (ie, 10 time points × 20 participants)] and fed [n = 200 (ie, 10 time points × 20 participants)] conditions. (C and D) Data were collected under preprandial/fasted conditions [n = 200 (ie, 10 times points × 20 participants)]. (E and F). Data were collected under postprandial conditions [n = 200 (ie, 10 times points × 20 participants). (G and H) Data were collected under level 1 hypoglycemia (ie, capillary glucose values ≥ 3.0 mmol/L and P < 0.01). (B) Bias: −14.50 ± 14.70; Slope: −0.363 ± 0.629 (P > 0.05). (C) Bias: −0.96 ± 0.70; Slope: −0.28 ± 0.06 (P < 0.001). (D) Bias: −17.6 ± 13.1; Slope: −2.0 ± 1.1 (P = 0.06). (E) Bias: −0.74 ± 1.01; Slope: −0.17 ± 0.06 (P < 0.01). (F) Bias: −11.4 ± 15.5; Slope: −0.6 ± 0.9 (P = 0.50). (G) Bias: −1.08 ± 0.79; Slope: −1.71 ± 0.22 (P < 0.001). (H) Bias: −24.2 ± 18.1; Slope: −38.1 ± 5.6 (P < 0.001). (I) Bias: −0.16 ± 0.05; Slope: −0.83 ± 0.97 (P < 0.01). (J) Bias: −0.19 ± 0.86; Slope: −13.82 ± 16.82 (P = 0.82). (K) Bias: −0.03 ± 0.06; Slope: −0.87 ± 0.74 (P = 0.60). (L) Bias: −1.56 ± 0.95; Slope: −15.07 ± 12.10 (P = 0.10).
Figure 1.
Figure 1.
Bland-Altman plots. Difference between continuous glucose monitoring (CGM) values and capillary blood glucose (CBG) measured by the Freestyle Freedom Lite (Abbott, Chicago, IL, USA) device, expressed as absolute (A, C, E, G, I, and K, in mmol/L) and relative (B, D, F, H, J, and L, in %) values. Y-axis shows the absolute (A, C, E, G, I, and K) or relative (B, D, F, H, J, and L) difference between CBG and CGM values at each study time point. X-axis shows the average glucose value at each study time point. Bias (black thick line), 95% CI (grey thin lines), and regression line (diagonal line, various colors) are shown. (A and B) Data were collected under preprandial/fasted [n = 200 (ie, 10 time points × 20 participants)] and fed [n = 200 (ie, 10 time points × 20 participants)] conditions. (C and D) Data were collected under preprandial/fasted conditions [n = 200 (ie, 10 times points × 20 participants)]. (E and F). Data were collected under postprandial conditions [n = 200 (ie, 10 times points × 20 participants). (G and H) Data were collected under level 1 hypoglycemia (ie, capillary glucose values ≥ 3.0 mmol/L and P < 0.01). (B) Bias: −14.50 ± 14.70; Slope: −0.363 ± 0.629 (P > 0.05). (C) Bias: −0.96 ± 0.70; Slope: −0.28 ± 0.06 (P < 0.001). (D) Bias: −17.6 ± 13.1; Slope: −2.0 ± 1.1 (P = 0.06). (E) Bias: −0.74 ± 1.01; Slope: −0.17 ± 0.06 (P < 0.01). (F) Bias: −11.4 ± 15.5; Slope: −0.6 ± 0.9 (P = 0.50). (G) Bias: −1.08 ± 0.79; Slope: −1.71 ± 0.22 (P < 0.001). (H) Bias: −24.2 ± 18.1; Slope: −38.1 ± 5.6 (P < 0.001). (I) Bias: −0.16 ± 0.05; Slope: −0.83 ± 0.97 (P < 0.01). (J) Bias: −0.19 ± 0.86; Slope: −13.82 ± 16.82 (P = 0.82). (K) Bias: −0.03 ± 0.06; Slope: −0.87 ± 0.74 (P = 0.60). (L) Bias: −1.56 ± 0.95; Slope: −15.07 ± 12.10 (P = 0.10).
Figure 2.
Figure 2.
Overnight continuous glucose monitoring (CGM) values in all glycogen storage disease type Ia patients (dark grey) and healthy volunteers (light grey). Mean (thick line) and 95%CI (shaded area) are shown. X-axis shows the time period (ie, 1:00-5:00 am). Y-axis shows the CGM values.
Figure 3.
Figure 3.
Overnight continuous glucose monitoring (CGM) course in participant 007 (light grey), compared to the average CGM values of the remaining 9 glycogen storage disease type Ia patients (dark grey). Mean (thick line) and 95%CI (shaded area) are shown. X-axis shows the time period (ie, 1:00-5:00 am). Y-axis shows the CGM values.

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