A high-protein breakfast induces greater insulin and glucose-dependent insulinotropic peptide responses to a subsequent lunch meal in individuals with type 2 diabetes

J Nutr. 2015 Mar;145(3):452-8. doi: 10.3945/jn.114.202549. Epub 2014 Dec 24.


Background: The previous meal modulates the postprandial glycemic responses to a subsequent meal; this is termed the second-meal phenomenon.

Objective: This study examined the effects of high-protein vs. high-carbohydrate breakfast meals on the metabolic and incretin responses after the breakfast and lunch meals.

Methods: Twelve type 2 diabetic men and women [age: 21-55 y; body mass index (BMI): 30-40 kg/m(2)] completed two 7-d breakfast conditions consisting of 500-kcal breakfast meals as protein (35% protein/45% carbohydrate) or carbohydrate (15% protein/65% carbohydrate). On day 7, subjects completed an 8-h testing day. After an overnight fast, the subjects consumed their respective breakfast followed by a standard 500-kcal high-carbohydrate lunch meal 4 h later. Blood samples were taken throughout the day for assessment of 4-h postbreakfast and 4-h postlunch total area under the curve (AUC) for glucose, insulin, C-peptide, glucagon, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide 1 (GLP-1).

Results: Postbreakfast glucose and GIP AUCs were lower after the protein (17%) vs. after the carbohydrate (23%) condition (P < 0.05), whereas postbreakfast insulin, C-peptide, glucagon, and GLP-1 AUCs were not different between conditions. A protein-rich breakfast may reduce the consequences of hyperglycemia in this population. Postlunch insulin, C-peptide, and GIP AUCs were greater after the protein condition vs. after the carbohydrate condition (second-meal phenomenon; all, P < 0.05), but postlunch AUCs were not different between conditions. The overall glucose, glucagon, and GLP-1 responses (e.g., 8 h) were greater after the protein condition vs. after the carbohydrate condition (all, P < 0.05).

Conclusions: In type 2 diabetic individuals, compared with a high-carbohydrate breakfast, the consumption of a high-protein breakfast meal attenuates the postprandial glucose response and does not magnify the response to the second meal. Insulin, C-peptide, and GIP concentrations demonstrate the second-meal phenomenon and most likely aid in keeping the glucose concentrations controlled in response to the subsequent meal. The trial was registered at www.clinicaltrials.gov/ct2/show/NCT02180646 as NCT02180646.

Keywords: GIP; GLP-1; glucagon; high carbohydrate; postprandial glucose; second-meal phenomenon; type 2 diabetes.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Mass Index
  • Breakfast*
  • C-Peptide / blood
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diet therapy*
  • Diet
  • Diet Records
  • Dietary Carbohydrates / administration & dosage*
  • Dietary Proteins / administration & dosage*
  • Energy Intake
  • Female
  • Gastric Inhibitory Polypeptide / blood*
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / diet therapy
  • Insulin / blood*
  • Lunch*
  • Male
  • Middle Aged
  • Postprandial Period / drug effects
  • Single-Blind Method
  • Young Adult


  • Blood Glucose
  • C-Peptide
  • Dietary Carbohydrates
  • Dietary Proteins
  • Insulin
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon

Associated data

  • ClinicalTrials.gov/NCT02180646