Incretin, insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial

Abstract

Aims/hypothesis 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/interpretation 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 glucoselowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research.

Nonfat milk attenuates acute hyperglycemia in individuals with android obesity: A randomized control trial

“…For example, the consumption of whey protein with a high glycemic meal decreased postprandial serum glucose in patients with diabetes (Jakubowicz et al., 2014). We recruited obese yet young, apparently healthy participants that exhibited fairly normal postprandial metabolic and vascular responses.…”

“…We found no significant differences in glycemic responses between the trials involving nonfat milk and those with the control drink that included the same amount of protein. These results confirm previous findings that at least some of the beneficial effects of milk on glycemic responses can be attributed to its protein quantity (Akhavan et al., 2010, 2014; Ballard et al., 2013; Elwood et al., 2010; Fekete et al., 2016; Gannon et al., 1992; Jakubowicz et al., 2014; Manders et al., 2014). …”

“…Importantly, previous studies investigating the effects of milk and milk protein on postprandial hyperglycemia employed less carbohydrate and more protein (Akhavan et al., 2010; Jakubowicz et al., 2014), allowing for a greater potential of protein to limit increases in blood glucose. The present findings indicate that a single serving of milk was effective in attenuating the glycemic effect of high‐carbohydrate meals at least in individuals with highly elevated android obesity.…”

“…Recent research has demonstrated favorable effects in glycemic management when dairy products are combined with high‐carbohydrate meals (Fekete et al., 2016; Panahi, El Khoury, Luhovyy, Goff, & Anderson, 2013; Panahi et al., 2013). The majority of relevant findings in this area attribute attenuated hyperglycemia to the insulinotropic properties of dairy proteins (Akhavan, Luhovyy, Brown, Cho, & Anderson, 2010; Fekete et al., 2016; Floyd, Fajans, Conn, Knopf, & Rull, 1966; Jakubowicz et al., 2014; Manders et al., 2014; Schmid, Schusdziarra, Schulte‐Frohlinde, Maier, & Classen, 1989; Schmid et al., 1992). In fact, milk‐derived proteins elicit dose‐dependent decreases in postprandial hyperglycemia when consumed with a high‐carbohydrate meal (Akhavan et al., 2010).…”

Protein ‘pre-loads’ in type 2 diabetes: what do we know and what do we need to find out?

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Abbreviations

CCKCholecystokinin GLP-1 Glucagon-like peptide-1To the Editor: We read with interest the Short Communication from Jakubowicz et al, published recently in Diabetologia [1]. The authors reported that acute administration of 50 g whey protein, in liquid form, 30 min before a high carbohydrate breakfast, substantially reduced postprandial glycaemia as compared with placebo in patients with type 2 diabetes, and there were concomitant increases in both glucagon-like peptide-1 (GLP-1) and insulin.

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