Whey Protein on Posprandial Glucose, Insulin GLP-1, GIP and DPP4 in Type 2 Diabetes (WheyGLP-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Daniela Jakubowicz, Tel Aviv University
ClinicalTrials.gov Identifier:
NCT01571622
First received: April 3, 2012
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Type 2 Diabetes Mellitus
Dietary Supplement: Whey before Breakfast
Dietary Supplement: Water before breakfast

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Tel Aviv University:

Primary Outcome Measures:
  • Glucose response [ Time Frame: During 4 hours meal challenge ] [ Designated as safety issue: No ]

    In all 25 subjects, the effects of whey protein ingestion posprandial glucose, will be measured. Thirty minutes prior to breakfast, subjects will preloaded with one of 2 alternatives:

    1. (250 ml) water
    2. Whey Protein Concentrate (WPC 80 %), 45 gr dissolved in 250 ml of water


Secondary Outcome Measures:
  • Insulin GLP-1, GIP and DPP4 [ Time Frame: During 4 hours after meal challange ] [ Designated as safety issue: No ]

    In all 25 subjects, the effects of whey protein on posprandial insulin, C- peptide, GIP, GLP-1, and dipeptil dipeptidase-4 (DPP-4) after standardized breakfast will be measured. Thirty minutes prior to breakfast, subjects will preloaded with one of 2 alternatives:

    1. (250 ml) water
    2. Whey Protein Concentrate (WPC 80 %), 45 gr dissolved in 250 ml of water


Enrollment: 19
Study Start Date: April 2012
Study Completion Date: September 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Water before breakfast
Each patient will consume a high-GI breakfast (white bread). Each subject will be pretreated 30 min before breakfast with 250 ml of water
Dietary Supplement: Whey before Breakfast
After consumption of whey before breakfast samples will be taken every 30 minutes for quantification of glucose, insulin, GlP-1 and GIP
Dietary Supplement: Water before breakfast
After water before breakfast the blood samples will be taken every 30 min for quantification of glucose, insulin, GLP-1 and GIP,
Experimental: Whey before breakfast
Each patient will consume a high-GI breakfast (white bread). Each subject will be pretreated 30 min before breakfast with Whey Protein Concentrate (WPC 80 %) 45 gr dissolved in 250 ml of water\
Dietary Supplement: Whey before Breakfast
After consumption of whey before breakfast samples will be taken every 30 minutes for quantification of glucose, insulin, GlP-1 and GIP
Dietary Supplement: Water before breakfast
After water before breakfast the blood samples will be taken every 30 min for quantification of glucose, insulin, GLP-1 and GIP,

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Type 2 diabetic patients
  2. Duration of diabetes: 1-10 years
  3. Subjects ≥ 40 and ≤70 years of age
  4. Metformin therapy and all oral antidiabetic medication will be allowed
  5. Overweight or obese (BMI: 25 to 35 kg/m2)
  6. Normal liver and kidney function
  7. Normal thyroid function
  8. Read and understood the informed consent form and signed it voluntarily

Exclusion Criteria:

  1. Liver, heart, kidney, lung, infectious, neurological, psychiatric, immunological or neoplastic diseases.
  2. Type 1 or insulin treated diabetes.
  3. Pregnancy or lactation
  4. Illicit drug abuse or alcoholism
  5. Subject treated with insulin or treatment with degradation-resistant GLP-1R agonists (Exendin-4) or similar and DPP4 inhibitors (Januvia)
  6. Subjects taking anoretic drugs
  7. Subjects on steroid treatment
  8. Subjects known by the principal investigator to be unable to cooperate for any reason.
  9. Known hypersensitivity to milk components
  10. Subjects after bariatric surgery.

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  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01571622

Locations
Israel
Diabetes Unit E. Wolfson Hospital
Holon, Tel Aviv, Israel, 58100
Sponsors and Collaborators
Tel Aviv University
Investigators
Principal Investigator: Daniela Jakubowicz, MD Diabetes Unit E. Wolfson Medical Center Tel Aviv University
  More Information

No publications provided

Responsible Party: Daniela Jakubowicz, Professor Daniela Jakubowicz MD, Tel Aviv University
ClinicalTrials.gov Identifier: NCT01571622     History of Changes
Other Study ID Numbers: 0175-11-WOMC
Study First Received: April 3, 2012
Last Updated: March 27, 2014
Health Authority: Israel: Ethics Commission

Keywords provided by Tel Aviv University:
Whey protein
type 2 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014