title: The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study.
abstract: BACKGROUND
  Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved.
  
  
  METHODS
  In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses.
  
  
  RESULTS
  Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens.
  
  
  CONCLUSIONS
  Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day.
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.|First Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Belinova
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kahleova
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Malinska
authors.affiliation: Laboratory of Immunoanalysis, University Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Topolcan
authors.affiliation: Laboratory of Immunoanalysis, University Hospital in Pilsen, Pilsen, Czech Republic.
authors.forename: Jindra
authors.initials: J
authors.lastname: Windrichova
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Olena
authors.initials: O
authors.lastname: Oliyarnyk
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kazdova
authors.affiliation: Department of Steroid Hormones and Proteohormones, Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.affiliation: Department of Diabetology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Terezie
authors.initials: T
authors.lastname: Pelikanova
mesh_terms: D000328:Adult; D000368:Aged; D001835:Body Weight; D031204:Caloric Restriction / Q000379:methods*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D006815:Hunger / Q000502:physiology; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D062407:Meals / Q000502:physiology / Q000523:psychology; D008875:Middle Aged; D010191:Pancreatic Polypeptide / Q000097:blood; D019894:Peptide YY / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054439:Ghrelin; D020738:Leptin; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D052216:Glucagon-Like Peptide 1