Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK.
Int J Obes (Lond). 2012 Dec;36(12):1564-70. doi: 10.1038/ijo.2011.274. Epub 2012 Jan 24.
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.
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).
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.
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.
普拉德-威利综合征（PWS）是一种遗传性神经发育障碍，在儿童时期有几个营养阶段，从喂养不良开始，经过正常饮食而不肥胖，到贪食和危及生命的肥胖，发病年龄不一。我们研究了食欲激素的差异是否可以解释患有 PWS 的幼儿异常进食行为的发展。
在这项横断面研究中，我们招募了 7 个月至 5 岁的 PWS 患儿（n=42）和对照组（n=9）。母亲接受了有关饮食行为的访谈，并计算了体重指数（BMI）。采集空腹血样检测胰岛素、瘦素、血糖、肽 YY（PYY）、胃饥饿素和胰多肽（PP）。
无论年龄如何，PWS 患儿的进食行为与任何激素或胰岛素抵抗水平之间均无显著关系。PWS 患儿的空腹血浆瘦素水平显著升高（平均值±标准差：22.6±12.5 与 1.97±0.79ng/ml，P=0.005），而 PP 水平显著降低（22.6±12.5 与 69.8±43.8pmol/l，P<0.001），与对照组相比，这与年龄、BMI、胰岛素抵抗或 IGF-1 水平无关。然而，两组间的血浆胰岛素、胰岛素抵抗或胃饥饿素水平无显著差异，尽管 PYY 随年龄而非 BMI 下降更快。
即使在 5 岁以下，PWS 也与食欲抑制性 PP 水平降低有关，这与年龄较大的儿童和成人相似。在这些患有 PWS 的幼儿中并未出现高胃饥饿素血症或低胰岛素血症。这些食欲激素的变化与向特征性贪食阶段过渡的时间无关。然而，这些食欲激素效应通路（例如，副交感神经和中枢神经系统）的异常和/或延迟发育或敏感性可能与低 PP 水平以及后来的高胃饥饿素血症或低胰岛素血症相互作用，导致 PWS 患者贪食。
