ABSTRACT: 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.