title: A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1.
  
  
  METHODS
  Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays.
  
  
  RESULTS
  Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets.
  
  
  CONCLUSIONS
  Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ACTRN12612000600842.
  
  
  BACKGROUND
  The study was funded by Meyer Nutriceuticals.
authors.affiliation: Discipline of Medicine, Royal Adelaide Hospital North Terrace, Adelaide, SA 5000, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: H L
authors.initials: HL
authors.lastname: Checklin
authors.forename: J M
authors.initials: JM
authors.lastname: Wishart
authors.forename: J E
authors.initials: JE
authors.lastname: Stevens
authors.forename: K L
authors.initials: KL
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
authors.forename: J H
authors.initials: JH
authors.lastname: Meyer
authors.forename: C K
authors.initials: CK
authors.lastname: Rayner
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007082:Ileum / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007850:Lauric Acids / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D013608:Tablets, Enteric-Coated / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007850:Lauric Acids; D013608:Tablets, Enteric-Coated; C030358:lauric acid; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008687:Metformin