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Pediatrics

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

International Journal of Obesity volume 36, pages 1564–1570 (2012)Cite this article

Subjects

Abstract

Objective:

Prader–Willi syndrome (PWS) is a genetic neurodevelopmental disorder with several nutritional phases during childhood proceeding from poor feeding, through normal eating without and with obesity, to hyperphagia and life-threatening obesity, with variable ages of onset. We investigated whether differences in appetite hormones may explain the development of abnormal eating behaviour in young children with PWS.

Subjects:

In this cross-sectional study, children with PWS (n=42) and controls (n=9) aged 7 months–5 years were recruited. Mothers were interviewed regarding eating behaviour, and body mass index (BMI) was calculated. Fasting plasma samples were assayed for insulin, leptin, glucose, peptide YY (PYY), ghrelin and pancreatic polypeptide (PP).

Results:

There was no significant relationship between eating behaviour in PWS subjects and the levels of any hormones or insulin resistance, independent of age. Fasting plasma leptin levels were significantly higher (mean±s.d.: 22.6±12.5 vs 1.97±0.79 ng ml−1, P=0.005), and PP levels were significantly lower (22.6±12.5 vs 69.8±43.8 pmol l−1, P<0.001) in the PWS group compared with the controls, and this was independent of age, BMI, insulin resistance or IGF-1 levels. However, there was no significant difference in plasma insulin, insulin resistance or ghrelin levels between groups, though PYY declined more rapidly with age but not BMI in PWS subjects.

Conclusion:

Even under the age of 5 years, PWS is associated with low levels of anorexigenic PP, as in older children and adults. Hyperghrelinaemia or hypoinsulinaemia was not seen in these young children with PWS. Change in these appetite hormones was not associated with the timing of the transition to the characteristic hyperphagic phase. However, abnormal and/or delayed development or sensitivity of the effector pathways of these appetitive hormones (for example, parasympathetic and central nervous system) may interact with low PP levels, and later hyperghrelinaemia or hypoinsulinaemia, to contribute to hyperphagia in PWS.

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Acknowledgements

Financial support from Baily Thomas Charitable Fund, the Health Foundation, NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for Cambridgeshire and Peterborough (AJH) and UK Medical Research Council (APG). We thank study participants, PWSA-UK and Addenbrookes Hospital consultants (particularly Miss Allen) for help with recruitment, Nicola Matache (Addenbrookes Hospital, Cambridge), Michael Patterson and Mohammad Ghatei (Section of Investigative Medicine, Imperial College London) for performing assays.

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  1. Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK

    A P Goldstone

  2. Department of Psychiatry, Section of Developmental Psychiatry, University of Cambridge, Cambridge, UK

    A J Holland, J V Butler & J E Whittington

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  1. A P Goldstone
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Correspondence to A P Goldstone.

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Goldstone, A., Holland, A., Butler, J. et al. Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome. Int J Obes 36, 1564–1570 (2012). https://doi.org/10.1038/ijo.2011.274

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