title: Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3-36 in healthy overweight/obese humans.
abstract: Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3-36 and ghrelin in overweight/obese healthy humans.
authors.affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Sine H
authors.initials: SH
authors.lastname: Knudsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Karstoft
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D004435:Eating / Q000502:physiology; D005260:Female; D054439:Ghrelin / Q000378:metabolism*; D006262:Health; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D062407:Meals / Q000502:physiology*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D050177:Overweight / Q000378:metabolism / Q000503:physiopathology*; D010446:Peptide Fragments / Q000378:metabolism*; D019894:Peptide YY / Q000378:metabolism*; D012528:Satiety Response / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)
keywords: appetite; glucotoxicity; gut hormones; hunger; obesity