Exaggerated secretion of glucagon-like peptide-1 (GLP-1) could cause reactive hypoglycaemia.
The plasma concentrations of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1) are abnormally high after oral glucose in partially gastrectomised subjects with reactive hypoglycaemia, suggesting a causal relationship. Because of the glucose-dependency of its effects, it is impossible to induce hypoglycaemia in normal subjects in the basal state by exogenous GLP-1, regardless of dose. To further assess the role of the incretin hormones in reactive hypoglycaemia, we reproduced the glucose and hormone profiles of the patients with reactive hypoglycaemia in 8 healthy volunteers in 4 separate protocols: 1) i.v. infusion of glucose (25 g) alone, 2) glucose together with i.v. GLP-1 infusion, and 3) and 4) glucose together with i.v. infusion of the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), at two different infusion rates. The plasma glucose, GLP-1 and GIP concentrations (low dose) obtained were comparable with those of the patients. With GLP-1, infusion of a total of 33.4 +/- 1.3 g glucose was required to obtain plasma glucose concentrations similar to those obtained by glucose infusion alone; with low GIP, 28.0 +/- 1.2 g and with high GIP 38.4 +/- 3.5 g. Insulin concentrations increased 10-fold with GLP-1 compared with i.v. glucose alone, but less with high and low GIP. In contrast, C-peptide concentrations were similar after GLP-1 and high GIP. After termination of i.v. glucose the lowest glucose concentrations were 4.5 (3.7-4.9) (median, range) for glucose alone; 2.4 (1.9-2.8) mmol/l with GLP-1; 3.7 (2.6-4.0) with low GIP and 3.3 (2.1-4.2) with high GIP. Thus, the exaggerated GLP-1 response to nutrients in patients with accelerated gastric emptying could be responsible for their high incidence of postprandial reactive hypoglycaemia.
Toft-Nielsen
M
M
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.
Madsbad
S
S
Holst
J J
JJ
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D004377:Dumping Syndrome / Q000150:complications; D005260:Female; D005743:Gastrectomy; D005746:Gastric Emptying / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*
D001786:Blood Glucose; D002096:C-Peptide; D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose