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13C-magnetic resonance spectroscopy; a viable technique to study overnight liver glycogen depletion and response to feeding in 8–12-year-old children

Published online by Cambridge University Press:  30 August 2022

E.J. Simpson
Affiliation:
School of Life Sciences, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK,
A.M.H. Horstman
Affiliation:
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
S.J. Bawden
Affiliation:
Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
A. Spicer
Affiliation:
Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
N. Darwish
Affiliation:
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
P. Gowland
Affiliation:
Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
D. Breuillé
Affiliation:
Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
I.A. Macdonald
Affiliation:
School of Life Sciences, Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK, Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland.
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Abstract

Type
Abstract
Copyright
Copyright © The Authors 2022

Owing to its role in maintaining glucose homeostasis, liver glycogen content can be an important marker of altered metabolism seen in disorders which impact health of children. Although 13C-magnetic resonance spectroscopy (13C-MRS) has been used extensively in research to non-invasively assess liver metabolites in adult health and disease, similar measurements in children are lacking. There is a paucity of normative data for liver glycogen concentration ([LGly]) in children to allow comparison with patient cohorts, and time-course assessment of [LGly] in response to feeding has not been reported. The present study quantified the depletion of [LGly] after an overnight fast, and subsequent response to consuming a mixed-macronutrient test drink (Milo®; Nestlé S.A.), using a randomised, controlled, open-label, crossover design. Sixteen (9F:7M) healthy, normal-weight prepubescent children (8–12y) were recruited. Following screening, a 4-day dietary record and accelerometery recording were made to estimate daily energy requirement and indicate dietary preferences. Participants subsequently attended the University on 4 occasions; 2 evening visits, each separated by ≥5days, and each directly followed by a morning visit. An individually tailored meal providing 35% daily energy requirement (60% of energy as carbohydrate, 20% protein, 20% fat) was consumed 3 h prior to evening assessments, with participants remaining fasted from this meal until the morning visit. [LGly] was assessed once in the fed (20:00hrs) and fasted state (08:00hrs) using 13C-MRS; Spectra acquired on a Philips 3T Achieva MRI system with a single-loop carbon surface coil (with integral proton decouple coils) placed over the liver for 15-minute acquisition (4096 averages). The glycogen peak area was normalised to an external reference and quantified by comparison with signal from a volume with known glycogen concentration. On morning visits, 200 ml Milo® containing 16 g carbohydrate (402kJ), or water was consumed within 10 min, with 13C-MRS measurements made hourly for the next 4 h. Data are expressed as the mean (SD). Fifteen children completed the study (10.0 (1.1) y, BMI percentile 34.4 (25.0), with 1 male dropping out after screening.

Children aged 8–12y tolerated the MR scanning protocol well, making it an acceptable technique to use in this age group. [LGly] decreased from 687.2 (161.4) to 503.9 (144.5) mmol⋅l-1 overnight (-24.7 (22.5) %), with between visit coefficient of variation for fasting [LGly] being 174.0 (13.8) %. The mean incremental responses of [LGly] to the test drink and water were significantly different (time-trend difference P < 0.001), with net iAUC being -85.7 (303.4) and -383.4 (369.8) mmol⋅l-1⋅240 min respectively (P < 0.01). Comparison with adult data (Reference Taylor and Magnusson1,Reference Bawden and Stephenson2) indicated that [LGly] may be higher in children, but percentage depletion overnight was of a similar magnitude (Reference Taylor and Magnusson1). These data indicate that consumption of 16 g of carbohydrate after an overnight fast maintained fasting [LGly] for 2 h and delayed the decrease in [LGly] seen with continued fasting.

References

Taylor, R, Magnusson, l, et al. (1996) Clin Invest 97, 126132.CrossRefGoogle Scholar
Bawden, SJ, Stephenson, MC, et al. (2014) Food & function 5, 22372242.CrossRefGoogle Scholar