Inappropriate glucagon response after oral compared with isoglycemic intravenous glucose administration in patients with type 1 diabetes

TY - JOUR

T1 - Inappropriate glucagon response after oral compared with isoglycemic intravenous glucose administration in patients with type 1 diabetes

AU - Hare, Kristine J

AU - Vilsbøll, Tina

AU - Holst, Jens Juul

AU - Knop, Filip K

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Hyperglucagonemia following oral glucose ingestion in patients with type 1 diabetes (and type 2 diabetes) has been claimed to result from impaired intraislet insulin inhibition of glucagon. We looked at plasma glucagon responses to the oral glucose tolerance test (OGTT) and isoglycemic intravenous glucose infusion (IIGI) in patients with type 1 diabetes. Nine patients without residual β-cell function [age: 25 ± 9 yr; body mass index (BMI): 24 ± 2 kg/m2; fasting plasma glucose (FPG): 9.5 ± 2.1 mM; Hb A1c: 8.4 ± 1.2% (mean ± SD)] and eight healthy subjects (age: 28 ± 5 yr; BMI: 24 ± 3 kg/m2; FPG: 5.3 ± 0.2 mM; Hb A1c: 5.0 ± 0.1%) were examined on two separate occasions: 4-h 50-g OGTT and IIGI. Isoglycemia during IIGIs was obtained using 53 ± 5 g of glucose in patients with type 1 diabetes and 30 ± 3 g in control subjects (P < 0.001), resulting in gastrointestinal-mediated glucose disposal [100% x (glucoseOGTT - glucoseIIGI/glucoseOGTT)] of -6 ± 9 and 40 ± 6% (P < 0.01), respectively. Equal glucagon suppression during the two glucose stimuli was observed in healthy subjects, whereas patients with type 1 diabetes exhibited less inhibition in response to OGTT compared with IIGI (AUC: 1,519 ± 129 vs. 1,240 ± 86 pM·4 h; P = 0.03). This difference was even more pronounced during the initial 40 min with paradoxical hypersecretion of glucagon during OGTT and suppression during IIGI (AUC: 37 ± 13 vs. -33 ± 16 pM·40 min; P = 0.02). These results suggest that the inappropriate glucagon response to glucose in patients with type 1 diabetes occurs as a consequence of the oral administration way, suggesting a role of the gastrointestinal tract, possibly via glucagonotropic signaling from gut hormones (e.g., glucose-dependent insulinotropic polypeptide), in type 1 diabetic hyperglucagonemia.

AB - Hyperglucagonemia following oral glucose ingestion in patients with type 1 diabetes (and type 2 diabetes) has been claimed to result from impaired intraislet insulin inhibition of glucagon. We looked at plasma glucagon responses to the oral glucose tolerance test (OGTT) and isoglycemic intravenous glucose infusion (IIGI) in patients with type 1 diabetes. Nine patients without residual β-cell function [age: 25 ± 9 yr; body mass index (BMI): 24 ± 2 kg/m2; fasting plasma glucose (FPG): 9.5 ± 2.1 mM; Hb A1c: 8.4 ± 1.2% (mean ± SD)] and eight healthy subjects (age: 28 ± 5 yr; BMI: 24 ± 3 kg/m2; FPG: 5.3 ± 0.2 mM; Hb A1c: 5.0 ± 0.1%) were examined on two separate occasions: 4-h 50-g OGTT and IIGI. Isoglycemia during IIGIs was obtained using 53 ± 5 g of glucose in patients with type 1 diabetes and 30 ± 3 g in control subjects (P < 0.001), resulting in gastrointestinal-mediated glucose disposal [100% x (glucoseOGTT - glucoseIIGI/glucoseOGTT)] of -6 ± 9 and 40 ± 6% (P < 0.01), respectively. Equal glucagon suppression during the two glucose stimuli was observed in healthy subjects, whereas patients with type 1 diabetes exhibited less inhibition in response to OGTT compared with IIGI (AUC: 1,519 ± 129 vs. 1,240 ± 86 pM·4 h; P = 0.03). This difference was even more pronounced during the initial 40 min with paradoxical hypersecretion of glucagon during OGTT and suppression during IIGI (AUC: 37 ± 13 vs. -33 ± 16 pM·40 min; P = 0.02). These results suggest that the inappropriate glucagon response to glucose in patients with type 1 diabetes occurs as a consequence of the oral administration way, suggesting a role of the gastrointestinal tract, possibly via glucagonotropic signaling from gut hormones (e.g., glucose-dependent insulinotropic polypeptide), in type 1 diabetic hyperglucagonemia.

KW - Adult

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptides

KW - Glucose

KW - Glucose Tolerance Test

KW - Humans

KW - Infusions, Intravenous

KW - Male

KW - Young Adult

U2 - 10.1152/ajpendo.00700.2009

DO - 10.1152/ajpendo.00700.2009

M3 - Journal article

C2 - 20103744

SN - 0193-1849

VL - 298

SP - E832-7

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

IS - 4

ER -