Liver glycogen stores via 13C magnetic resonance spectroscopy in healthy children: randomized, controlled study

Abstract

Background: Owing to its role in glucose homeostasis, liver glycogen concentration ([LGly]) can be a marker of altered metabolism seen in disorders that impact the health of children. However, there is a paucity of normative data for this measure in children to allow comparison with patients, and time-course assessment of [LGly] in response to feeding has not been reported. In addition, carbon-13 magnetic resonance spectroscopy (¹³C-MRS) is used extensively in research to assess liver metabolites in adult health and disease noninvasively, but similar measurements in children are lacking.

Objectives: The main objectives were to quantify the depletion of [LGly] after overnight fasting and the subsequent response to feeding.

Methods: In a randomly assigned, open-label, incomplete block design study, healthy, normal-weight children (8-12 y) attended 2 evening visits, each separated by ≥5 d and directly followed by a morning visit. An individually tailored, standardized meal was consumed 3-h prior to evening assessments. Participants then remained fasted until the morning visit. [LGly] was assessed once in the fed (20:00) and fasted state (08:00) using ¹³C-MRS. After the 8:00 assessment, 200 ml of a mixed-macronutrient drink containing 15.5 g (402 kJ) or 31 g carbohydrates (804 kJ), or water only, was consumed, with ¹³C-MRS measurements then performed hourly for 4 h. Each child was randomly assigned to 2 of 3 drink options across the 2 mornings. Data are expressed as mean (SD).

Results: Twenty-four children including females and males (13F:11M) completed the study [9.9 (1.1) y, BMI percentile 45.7 (25.9)]. [LGly] decreased from 377.9 (141.3) to 277.3 (107.4) mmol/L overnight; depletion rate 0.14 (0.15) mmol/L min. Incremental responses of [LGly] to test drinks differed (P < 0.001), with incremental net area under the curve of [LGly] over 4 h being higher for 15.5 g [-67.1 (205.8) mmol/L·240 min; P < 0.01] and 31 g carbohydrates [101.6 (180.9) mmol/L·240 min; P < 0.005] compared with water [-253.1 (231.2) mmol/L·240 min].

Conclusions: After overnight fasting, [LGly] decreased by 22.9 (25.1)%, and [LGly] incremental net area under the curve over 4 h was higher after subsequent consumption of 15.5 g and 31 g carbohydrates, compared to water. Am J Clin Nutr 20XX;xx:xx-xx.

Trial registration: ClinicalTrials.gov NCT04278209.

Keywords: carbohydrate metabolism; fasting; feeding; gastric emptying; muscle glycogen concentration.