Kuppens R J, Delhanty P J D, Huisman T M, van der Lely A J, Hokken-Koelega A C S
Dutch Growth Research Foundation, Rotterdam, The Netherlands.
Subdivision of Endocrinology, Department of Pediatrics, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
Clin Endocrinol (Oxf). 2016 Sep;85(3):488-94. doi: 10.1111/cen.13036. Epub 2016 Feb 23.
Prader-Willi syndrome (PWS) is characterized by hyperphagia with impaired satiety. PWS patients have very high acylated ghrelin (AG) with normal unacylated ghrelin (UAG) levels, resulting in an elevated AG/UAG ratio, suggesting an intrinsic defect in the ghrelin regulation. Normally, food intake induces satiety and a drop in AG and UAG levels, but it is unknown if these levels also decline in PWS.
To evaluate whether the high AG levels in PWS decline in response to glucose intake during an oral glucose tolerance test (OGTT), and to investigate the effects of growth hormone (GH) treatment on this response.
Serum levels of AG, UAG and AG/UAG ratio during an OGTT were determined in 24 GH-treated patients with PWS (median age 19·0, range 14·2-25·9 years) and in 10 GH-stop patients (of whom five were in GH-treated group; 18·5, 14·5-20·3 years).
In GH-treated and GH-stop young adults with PWS, there was a sharp decline of AG levels and a decrease of UAG levels in the first 30 min after the glucose load, which resulted in a lower AG/UAG ratio. GH-treated patients had significantly lower AG levels than GH-stop patients at baseline and during the OGTT. All UAG levels and AG/UAG ratios were lower in the GH-treated patients, although not significantly.
In young adults with PWS, an oral glucose load significantly reduces AG and UAG levels, suggesting normal regulation of the ghrelin axis by food intake. GH treatment results in lower AG levels at baseline and during OGTT, suggesting a more favourable metabolic profile. Our findings might suggest that the impaired satiety is not the result of an abnormal response of the orexigenic ghrelin to food intake.
普拉德-威利综合征（PWS）的特征为食欲亢进且饱腹感受损。PWS患者的酰基化胃饥饿素（AG）水平非常高，而去酰基化胃饥饿素（UAG）水平正常，导致AG/UAG比值升高，提示胃饥饿素调节存在内在缺陷。正常情况下，食物摄入会引发饱腹感并使AG和UAG水平下降，但PWS患者中这些水平是否也会下降尚不清楚。
评估口服葡萄糖耐量试验（OGTT）期间PWS患者的高AG水平是否会因葡萄糖摄入而下降，并研究生长激素（GH）治疗对该反应的影响。
测定了24例接受GH治疗的PWS患者（中位年龄19.0岁，范围14.2 - 25.9岁）和10例停用GH的患者（其中5例曾接受GH治疗；年龄18.5岁，范围14.5 - 20.3岁）在OGTT期间的血清AG、UAG水平及AG/UAG比值。
在接受GH治疗和停用GH的PWS年轻成人中，葡萄糖负荷后最初30分钟内AG水平急剧下降，UAG水平降低，导致AG/UAG比值降低。接受GH治疗的患者在基线和OGTT期间的AG水平显著低于停用GH的患者。接受GH治疗的患者所有UAG水平和AG/UAG比值均较低，尽管差异无统计学意义。
在PWS年轻成人中，口服葡萄糖负荷显著降低AG和UAG水平，提示食物摄入对胃饥饿素轴有正常调节作用。GH治疗导致基线和OGTT期间AG水平较低，提示代谢状况更有利。我们的研究结果可能表明，饱腹感受损并非促食欲胃饥饿素对食物摄入异常反应的结果。
