Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial
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.
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.
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.
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.
- Elahi D (1996) In praise of the hyperglycemic clamp. A method for assessment of beta-cell sensitivity and insulin resistance. Diabetes Care 19:278–286 CrossRef
- Bonuccelli S, Muscelli E, Gastaldelli A et al (2009) Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms. Am J Physiol Endocrinol Metab 297:E532–E537 CrossRef
- Fehse F, Trautmann M, Holst JJ et al (2005) Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 90:5991–5997 CrossRef
- Balas B, Baig MR, Watson C et al (2007) The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab 92:1249–1255 CrossRef
- Gunnarsson PT, Winzell MS, Deacon CF et al (2006) Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice. Endocrinology 147:3173–3180 CrossRef
- Frid AH, Nilsson M, Holst JJ, Bjorck IM (2005) Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr 82:69–75
- Gribble FM, Manley SE, Levy JC (2001) Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166). Diabetes Care 24:1221–1225 CrossRef
- Kitabchi AE, Kaminska E, Fisher JN et al (2000) Comparative efficacy and potency of long-term therapy with glipizide or glyburide in patients with type 2 diabetes mellitus. Am J Med Sci 319:143–148 CrossRef
- Cozma LS, Luzio SD, Dunseath GJ, Langendorg KW, Pieber T, Owens DR (2002) Comparison of the effects of three insulinotropic drugs on plasma insulin levels after a standard meal. Diabetes Care 25:1271–1276 CrossRef
- Jakubowicz D, Froy O (2013) Biochemical and metabolic mechanisms by which dietary whey protein may combat obesity and type 2 diabetes. J Nutr Biochem 24:1–5 CrossRef
- Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial
Volume 57, Issue 9 , pp 1807-1811
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- 1. Diabetes Unit, E. Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 62 Halochamim, 58100, Holon, Israel
- 2. Institute of Biochemistry, Food Science and Nutrition, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, 1 Herzel, 76100, Rehovot, Israel
- 3. Department of Clinical Sciences, Faculty of Medicine, Lund University, Sölvegatan 19, 221 84, Lund, Sweden
- 4. Epidemiology and Research Unit, E. Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, 62 Halochamim, 58100, Holon, Israel