Type 2 Diabetes Mellitus Clinical Trial
Official title:
Effect of Whey Protein Concentrate on Postprandial Glycemic Insulin, Active and Intact GLP-1and GIP, and DPP-4 Response in Type 2 Diabetic Patients
The aim of the present study is to examine the therapeutic effect of whey protein concentrate (WPC 80) in adult subjects with in type 2 diabetes. Whey protein will be administered before breakfast and its effects on posprandial glucose, insulin, c-peptide, intact and total GIP and GLP-1, and DPP-4 plasma levels will be assessed.
Milk and dairy product consumption has been associated with lower risk of metabolic
disorders and cardiovascular diseases (1). A population-based prospective study (CARDIA)
revealed that dairy consumption was inversely associated with the prevalence of all
components of the insulin resistance syndrome (IRS) in overweight individuals (2).
Whey accounts for about 20% of whole milk protein, while casein accounts for the rest. Whey
protein is a source of bioactive components and branch chained amino acids (BCAAs) which
could play a further role in the control of food intake and management of glucose
metabolism, obesity and diabetes (1,3,4).
Whey protein appears to have insulinotropic and glucose lowering properties in healthy
adults (6-9), and also in individuals with type 2 diabetes (10,11). The magnitude of
postprandial blood glucose reduction following ingestion of whey protein is comparable to
that observed with pharmaceutical interventions such as sulfonylureas (12) or nateglinide
(13). These findings imply an important role for whey protein in the management of type 2
diabetes (10).
Whey protein seems to induce insulinotropic/β-cell-stimulating and glucose lowering effects
via bioactive peptides generated during gastrointestinal digestion of BCAAs contained in
β-lactoglobulin, the major whey protein (14).
These bioactive peptides stimulate the release of several gut hormones, especially the
incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1
(GLP-1), which potentiate insulin secretion from β-cells and are also associated with the
control of food intake (9, 15-17). Increased plasma levels of GIP and GLP-1 have been
reported following whey ingestion in patients with type 2 diabetes (10). The stimulatory
effect of whey protein on GLP-1 is especially important since it has been shown that
postprandial GLP-1 secretion is reduced in type 2 diabetes (18).
The bioactive peptides generated from whey protein may also serve as endogenous inhibitors
of dipeptidyl peptidase-4 (DPP-4) in the proximal gut, preventing incretin (GIP and GLP-1)
degradation (19, 20). Indeed, recently DPP-4 inhibitors have been found and identified in
Whey protein (21). All these may reduce postprandial blood glucose levels.
Incretin action is enhanced by whey protein ingestion, possibly through incretin degradation
via inhibition of DPP-4 (19,20). This is important in light of several incretin-based
therapies such as continuous administration of GLP-1 (19), treatment with
degradation-resistant GLP-1R agonists (Exendin-4) (15,23-25), and therapy with DPP-4
inhibitors (Sitagliptin, Liraglutide and others gliptines ) (15,23-27) all of which have
lead to substantial improvements in glucose control and β-cell function in subjects with
type 2 diabetes.
Whey protein stimulates GLP-1 secretion and prevents its inactivation by DPP 4. Thus, by
potentiating GLP-1 secretion and enhancing its action, (15), whey protein may represent a
valuable tool for treating type 2 diabetes.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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