Glucose intolerance in acromegaly is driven by low insulin secretion; results from an intravenous glucose tolerance test

<bold>Purpose: </bold>Insulin sensitivity (S-i) and its role in glucose intolerance of acromegaly has been extensively evaluated. However, data on insulin secretion is limited. We aimed to assess stimulated insulin secretion using an intravenous glucose tolerance test (IVGTT) in active acromegaly. <bold>Methods: </bold>We performed an IVGTT in 25 patients with active acromegaly (13 normal glucose tolerance [NGT], 6 impaired glucose tolerance [IGT] and 6 diabetes mellitus [DM]) and 23 controls (8 lean NGT, 8 obese NGT and 7 obese IGT). Serum glucose and insulin were measured at 20 time points along the test to calculate S-i and acute insulin response (AIRg). Medical treatment for acromegaly or diabetes was not allowed. <bold>Results: </bold>In acromegaly, patients with NGT had significantly (p for trend < 0.001) higher AIRg (3383 +/- 1082 pmol*min/L) than IGT (1215 +/- 1069) and DM (506 +/- 600). AIRg was higher in NGT (4764 +/- 1180 pmol*min/L) and IGT (3183 +/- 3261) controls with obesity than NGT (p = 0.01) or IGT (p = 0.17) acromegaly. S-i was not significantly lower in IGT (0.68 [0.37, 0.88] 10(6)*L/pmol*min) and DM (0.60 [0.42, 0.84]) than in NGT (0.81 [0.58, 1.55]) patients with acromegaly. NGT (0.33 [0.30, 0.47] 10(6)*L/pmol*min) and IGT (0.37 [0.21, 0.66]) controls with obesity had lower S-i than NGT (p = 0.001) and IGT (p = 0.43) acromegaly. <bold>Conclusion: </bold>We demonstrated that low insulin secretion is the main driver behind glucose intolerance in acromegaly. Compared to NGT and IGT controls with obesity, patients with NGT or IGT acromegaly had higher S-i. Together, these findings suggest that impaired insulin secretion might be a specific mechanism for glucose intolerance in acromegaly.