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

March 27, 2014 updated by: Daniela Jakubowicz, Tel Aviv University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
    • Tel Aviv
      • Holon, Tel Aviv, Israel, 58100
        • Diabetes Unit E. Wolfson Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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,

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose response
Time Frame: During 4 hours meal challenge

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
During 4 hours meal challenge

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin GLP-1, GIP and DPP4
Time Frame: During 4 hours after meal challange

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
During 4 hours after meal challange

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tel Aviv University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

April 3, 2012

First Submitted That Met QC Criteria

April 3, 2012

First Posted (Estimate)

April 5, 2012

Study Record Updates

Last Update Posted (Estimate)

March 31, 2014

Last Update Submitted That Met QC Criteria

March 27, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0175-11-WOMC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes Mellitus

Clinical Trials on Whey before Breakfast

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe