title: Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial.
abstract: OBJECTIVE
  Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes.
  
  
  METHODS
  In a randomised, open-label crossover clinical trial, we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin. These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. Participants were randomised using a coin flip. The primary endpoints of the study were plasma concentrations of glucose, intact GLP-1 and insulin during the 30 min following meal ingestion.
  
  
  RESULTS
  In each group, 15 patients were analysed. The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey pre-load with a uniform reduction during both early and late phases. Insulin and C-peptide responses were both significantly higher (by 105% and 43%, respectively) with whey pre-load. Notably, the early insulin response was 96% higher after whey. Similarly, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey pre-load. Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups.
  
  
  CONCLUSIONS
  In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early prandial and late insulin secretion, augmented tGLP-1 and iGLP-1 responses and reduced postprandial glycaemia in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research.
authors.affiliation: Diabetes Unit, E. Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 62 Halochamim, 58100, Holon, Israel, daniela.jak@gmail.com.
authors.forename: Daniela
authors.initials: D
authors.lastname: Jakubowicz
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Mona
authors.initials: M
authors.lastname: Boaz
authors.forename: Zohar
authors.initials: Z
authors.lastname: Landau
authors.forename: Yosefa
authors.initials: Y
authors.lastname: Bar-Dayan
authors.forename: Tali
authors.initials: T
authors.lastname: Ganz
authors.forename: Maayan
authors.initials: M
authors.lastname: Barnea
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008894:Milk Proteins / Q000627:therapeutic use*; D000067816:Whey Proteins
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D008894:Milk Proteins; D000067816:Whey Proteins; D052216:Glucagon-Like Peptide 1