Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis

Abstract

Aims To examine plasma glucagon responses to oral and intravenous ( iv) glucose in patients with chronic pancreatitis (CP) and either normal glucose tolerance (NGT), secondary impaired glucose tolerance (IGT) or secondary diabetes mellitus (DM). Methods Eleven patients with CP and NGT, 6 patients with CP and secondary IGT, 7 patients with CP and secondary non-insulin requiring DM, and 8 healthy subjects were examined with an oral glucose tolerance test (OGTT) and an iv glucose tolerance test (IVGTT). Results In the CP groups, significant differences (increasing with the degree of glucose intolerance) in glucagon responses during the first hour of OGTT compared to IVGTT were observed (CP + NGT: − 13 ± 22 vs. − 88 ± 17, p = 0.02; CP + IGT: 3 ± 17 vs. − 87 ± 19, p = 0.01; CP + DM: 94 ± 27 vs. − 78 ± 16 1 h × pmol/l (mean ± SEM), p < 0.001). Glucagon was suppressed equally following OGTT and IVGTT in the healthy subjects (− 103 ± 22 vs. − 131 ± 19 1 h × pmol/l; p = NS). IVGTT suppressed glucagon similarly in all groups except for a slightly impaired suppression in the CP + DM-group compared to healthy subjects. Conclusions These results suggest that along with the development of secondary glucose intolerance in patients with CP, the suppression of glucagon by oral glucose is gradually lost and substituted by a paradoxical stimulation of secretion, while the suppression by iv glucose is maintained. This might indicate a glucagon stimulatory mechanism of gastrointestinal origin in CP patients.