Effect of oral glucose on acylated and total ghrelin secretion in acromegalic patients.

Objective: The pathophysiology of ghrelin secretion in acromegaly is unclear. Our aim was to study circulating fasting ghrelin levels and their response to oral glucose in acromegalic patients and normal control subjects.

Design And Patients: 9 acromegalic patients (4 male, 5 female; 59.4+/-3.6 years; 28.6+/-1.0 kg/m2) and 9 age and BMI matched healthy control subjects (4 male, 5 female; 59.1+/-1.4 years; 26.5+/-0.8 kg/m2) were included. We obtained blood samples for glucose, insulin, GH, total ghrelin and acylated ghrelin at times 0, 30, 60, 90 and 120 minutes after 75 g of oral glucose.

Results: Fasting GH and IGF-I were statistically different between patients and controls: GH (microg/l): 6.7+/-1.4 vs. 0.8+/-0.4, p<0.01; IGF-I (ng/ml): 414+/-75 vs. 86+/-6, p<0.01. Fasting total ghrelin (pg/ml) were similar in the patient and in the control group, 916+/-132 vs. 844+/-169, p=ns. In both groups total ghrelin levels decreased during oral glucose, and nadir total ghrelin was lower than fasting ghrelin: patients: 916+/-132 vs. 747+/-95, p<0.05; controls: 844+/-169 vs. 625+/-90, p<0.05). The AUCs of total ghrelin (pg/ml*min) were not different between the two groups: 98953+/-13052 vs. 83773+/-13096, p=ns). Fasting acylated ghrelin (pg/ml) were similar in the patient and the control group 65+/-13 pg/ml vs.74+/-14 pg/ml, p=ns. In both groups acylated ghrelin levels decreased during oral glucose, and nadir acylated ghrelin levels were lower than basal acylated ghrelin levels: patients: 65+/-13 vs. 42+/-6, p<0.05; controls: 74+/-14 pg/ml vs. 37+/-4 pg/ml, p<0.05). The AUCs of acylated ghrelin (pg/ml*min) were not different between the two groups: patients: 6173+/-992 vs. controls 8648+/-2742, p=ns). In acromegalic patients there was a negative correlation between fasting, both total and acylated, ghrelin and both fasting and post oral glucose insulin levels.

Conclusions: These data suggest that circulating total and acylated ghrelin in acromegaly is regulated by insulin and not by GH hypersecretion.