Incretin and islet hormone responses to meals of increasing size in healthy subjects.
BACKGROUND
Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through the stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known.


OBJECTIVE
The objective of the study was to explore the adaptation of incretin and islet hormones after mixed meals of increasing size in healthy subjects.


METHODS
Twenty-four healthy lean subjects ingested a standard breakfast after an overnight fast followed, after 4 hours, by a lunch of a different size (511, 743, and 1034 kcal) but with identical nutrient composition together with 1.5 g paracetamol. Glucose, insulin, C-peptide, glucagon, intact GLP-1, and glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured after the meals.


METHODS
Area under the 180-minute curve (AUC) for insulin, C-peptide, glucagon, GLP-1, and GIP and model-derived β-cell function and paracetamol appearance were calculated.


RESULTS
Glucose profiles were similar after the two larger meals, whereas after the smaller meal, there was a postpeak reduction below baseline to a nadir of 3.8 ± 0.1 mmol/L after 75 minutes (P < .001). The AUC for GLP-1, GIP, insulin, and C-peptide were significantly higher by increasing the caloric load as was β-cell sensitivity to glucose. In contrast, the AUC glucagon was the same for all three meals, although there was an increase in glucagon after the postpeak glucose reduction in the smaller meal. The 0- to 20-minute paracetamol appearance was increased by increasing meal size.


CONCLUSIONS
Mixed lunch meals of increasing size elicit a caloric-dependent insulin response due to increased β-cell secretion achieved by increased GIP and GLP-1 levels. The adaptation at larger meals results in identical glucose excursions, whereas after a lower caloric lunch, the insulin response is high, resulting in a postpeak suppression of glucose below baseline.
Department of Clinical Sciences (W.A., B.O., B.A.), Lund University, 221 84 Lund, Sweden; and Metabolic Unit (G.P., R.B., A.M.), Institute of Biomedical Engineering, Consiglio Nazionale delle Ricerche, 35127 Padova, Italy.
Wathik
W
Alsalim
Bilal
B
Omar
Giovanni
G
Pacini
Roberto
R
Bizzotto
Andrea
A
Mari
Bo
B
Ahrén
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D062407:Meals; D019518:Postprandial Period / Q000502:physiology*; D055815:Young Adult
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon