Acylated and unacylated ghrelin during OGTT in Prader-Willi syndrome: support for normal response to food intake

Background: 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. Objective: 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. Method: 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). Results: 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. Conclusions: 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.

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