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

BackgroundOwing to its role in glucose homeostasis, liver glycogen concentration ([LGly]) can be a marker of altered metabolism seen in disorders which impact 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. 13C-magnetic resonance spectroscopy (13C-MRS) is used extensively in research to non-invasively assess liver metabolites in adult health and disease, but similar measurements in children are lacking.ObjectiveThe main objectives were to quantify the depletion of [LGly] after overnight fasting, and the subsequent response to feeding.DesignIn a randomized, open-label, incomplete block design study, healthy, normal-weight children (8-12y) attended 2 evening visits, each separated by ≥5 days and directly followed by a morning visit. An individually tailored, standardized meal was consumed 3-hours prior to evening assessments. Participants then remained fasted until the morning visit. [LGly] was assessed once in the fed (20:00hrs) and fasted state (08:00hrs) using 13C-MRS. After the 8:00hrs assessment, 200ml of a mixed-macronutrient drink containing 15.5g (402kJ) or 31g carbohydrate (804kJ), or water only, was consumed, with 13C-MRS measurements then performed hourly for 4h. Each child was randomized to 2 of 3 drink options across the 2 mornings. Data are expressed as mean (SD).ResultsTwenty-four children (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-1 overnight; depletion rate 0.14(0.15) mmol·l-1·min-1. Incremental responses of [LGly] to test drinks differed (P<0.001), with incremental net AUC of [LGly] over 4h (i.netAUC240min) being higher for 15.5g (-67.1(205.8) mmol·l-1·240min; P<0.01) and 31g carbohydrate (101.6(180.9) mmol·l-1·240min; P<0.005) compared to water (-253.1(231.2) mmol·l-1·240min).ConclusionAfter overnight fasting, [LGly] decreased by 22.9(25.1)%, and [LGly] i.netAUC240min was higher after subsequent consumption of 15.5g and 31g carbohydrate, compared to water.Clinical Trial Registry number: NCT04278209 (www.clinicaltrials.gov