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

TY - JOUR

T1 - Glucagon suppression during OGTT worsens while suppression during IVGTT sustains alongside development of glucose intolerance in patients with chronic pancreatitis

AU - Knop, F K

AU - Vilsbøll, T

AU - Larsen, Steen

AU - Madsbad, S

AU - Holst, Jens Juul

AU - Krarup, Troels Magelund

N1 - Copyright 2010 Elsevier B.V. All rights reserved.

PY - 2010/9/24

Y1 - 2010/9/24

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Glucagon

KW - Glucose Intolerance

KW - Glucose Tolerance Test

KW - Humans

KW - Male

KW - Middle Aged

KW - Pancreatitis, Chronic

U2 - 10.1016/j.regpep.2010.05.011

DO - 10.1016/j.regpep.2010.05.011

M3 - Journal article

C2 - 20573586

SN - 0167-0115

VL - 164

SP - 144

EP - 150

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 2-3

ER -