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.

Desacyl ghrelin is influenced by changes in insulin concentration during an insulin tolerance test.

OBJECTIVE: Ghrelin, a gut-brain peptide, regulates energy homeostasis and glucose metabolism and is present in acylated and nonacylated form in the circulation. Although desacyl ghrelin (DAG), the predominant form of ghrelin, is associated with insulin sensitivity and improved metabolic state, not much is known about its direct regulation by insulin. We aimed to assess changes in DAG in response to the rapid increase in insulin concentration during an insulin tolerance test (ITT) in normal weight and obese subjects. DESIGN: We performed an observational single center study. An ITT was assessed in eight subjects (four males), median age of 29.9 years (range 19.6-42.0). DAG concentrations were measured at 20, 40, 60 and 90 min after insulin infusion. Homeostatic Model Assessment (HOMA) was calculated from fasting insulin and glucose. Body mass index (BMI) and waist circumference were assessed. RESULTS: Three subjects were obese (BMI ≥ 30 kg/m(2)), one subject was overweight (BMI = 25-30 kg/m(2)) and four subjects had normal weight (BMI = 18.5-25 kg/m(2)). Median DAG decreased after insulin infusion (90 pg/mL, p = 0.028), especially in normal weight subjects. Baseline DAG was lower in subjects with higher BMI (ρ = -0.76, p = 0.028) and higher fasting insulin (ρ = -0.76, p = 0.030). DAG changes correlated with fasting insulin levels (ρ = -0.85, p = 0.007), HOMA (ρ = -0.86, p = 0.007), BMI (ρ = -0.83, p = 0.010) and waist circumference (ρ = -0.93, p < 0.001). CONCLUSION: DAG levels rapidly decreased in response to insulin administration in normal subjects, but not in insulin-resistant obese who are in a state of relative DAG deficiency.