A retrospective in-depth analysis of continuous glucose monitoring datasets for patients with hepatic glycogen storage disease: Recommended outcome parameters for glucose management

Abstract

Continuous glucose monitoring (CGM) systems have great potential for real-time assessment of glycemic variation in patients with hepatic glycogen storage disease (GSD). However, detailed descriptions and in-depth analysis of CGM data from hepatic GSD patients during interventions are scarce. This is a retrospective in-depth analysis of CGM parameters, acquired in a continuous, real-time fashion describing glucose management in 15 individual GSD patients. CGM subsets are obtained both in-hospital and at home, upon nocturnal dietary intervention (n = 1), starch loads (n = 11) and treatment of GSD Ib patients with empagliflozin (n = 3). Descriptive CGM parameters, and parameters reflecting glycemic variation and glycemic control are considered useful CGM outcome parameters. Furthermore, the combination of first and second order derivatives, cumulative sum and Fourier analysis identified both subtle and sudden changes in glucose management; hence, aiding assessment of dietary and medical interventions. CGM data interpolation for nocturnal intervals reduced confounding by physical activity and diet. Based on these analyses, we conclude that in-depth CGM analysis can be a powerful tool to assess glucose management and optimize treatment in individual hepatic GSD patients.

Keywords: Fourier analysis; continuous glucose monitoring; diabetes mellitus; empagliflozin; glycogen storage disease; person-centered outcomes.

FIGURE 1

CGM subset I from the Dexcom Clarity Clinical Portal of the in‐hospital evaluation of P‐I‐1. The 5 days of in‐patient evaluation of P‐I‐1. Day 1 the current treatment of Nutridrink Juicy Style was evaluated. Days 2 and 3 the Maltodextrin (metaX—Institut für Diätetik GmbH) intervention is evaluated. Days 4 and 5 the UCCS intervention was evaluated. P, patient; UCCS, uncooked cornstarch

FIGURE 2

In‐depth data analysis of CGM subset III of GSD Ib patients treated with empagliflozin. A. P‐III‐1. B. P‐III‐2. C. P‐III‐3. P‐III‐1:1 = Empagliflozin 5 mg 1dd1 2 = Empagliflozin 5 mg 2dd; 3 = UCCS; P‐III‐2:1 = Empagliflozin 5 mg 1dd; 2 = UCCS 25 g 6dd; 3 = Empagliflozin 7.5 mg 1dd; 4 = Empagliflozin 5 mg 1dd and 2.5 mg 1dd; 5 = Empagliflozin 5 mg 2dd; 6 = Empagliflozin 5 mg 2dd (second dose giver at 20:00 instead of 16:00). P‐III‐3:1 = Empagliflozin 10 mg 2dd; 2 = Empagliflozin 15 mg 1dd and 10 mg 1dd. In blue the complete data is described, the data in black represent the interval between 1:00‐5:00 am. a. CGM concentrations; b. Descriptive data (mean, maximum, minimum, variation) between 1:00‐5:00 am; c. First order derivative of CGM concentrations; d. Second order derivate of CGM concentrations; e. Cumulative sum analysis method A (in blue, left axis) and cumulative sum analysis method B (in green, right axis); f. Fourier analysis spectrogram of CGM profile between 1:00‐5:00 am. The y‐axis displays the frequency of the sinusoidal CGM pattern in cycles per hour. The color displays the amplitude of the frequency (waterfall plot JOT color scheme). CGM, continuous glucose monitoring; dd, times per day; GSD, glycogen storage disease; P, patient; UCCS, uncooked cornstarch