Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly

Objective: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. Design and Methods: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. Results: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P < 0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r = 0.83, P < 0.01 and r = 0.65, P < 0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. Conclusion: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.