The Effect of Whey Protein Consumed as a Pre-meal on Postprandial Lipemia in Healthy and Subjects With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
Cardiovascular disease (CVD) is one of the most important and frequent causes of death. Postprandial lipidemia (PPL) is an independent risk factor for CVD, besides the traditional risk factors e.g. hypertension, high LDL-cholesterol, family disposition of CVD and type 2 diabetes (T2D). A high PPL is associated with an increased risk of myocardial infarction and stroke. Reduction of increased PPL, as a part of CVD prevention, is therefore pivotal. Especially in groups with increased risk of CVD, like the metabolic syndrome (MeS) and T2D. Identification of a simple diet-related method will possibly result in reduction of CVD in healthy as well as high-risk subjects. The aim of this project is to investigate the effect whey protein consumed as pre-meal prior to a fat-rich meal on responses of triglycerides and apolipoprotein B48 (ApoB48) in subjects with type 2 diabetes compared to healthy subjects. Secondarily the aim is to study the responses of glucose, insulin, glucagon, amino acids, inflammatory markers, incretins, rate of gastric emptying and metabolomics. Also satiety feeling will be measured. Investigators hypothesize that whey protein consumed 15 minutes prior to a fat-rich isocaloric meal reduces triglyceride- and ApoB48 responses more in type 2 diabetic subjects compared to healthy subjects. The investigators research will hopefully contribute to a better understanding of how PPL can be modified in a simple manner. It will promote innovation to the food industry for development and production of healthy food products, which can be applied in the fight against CVD in the background population in general and high-risk people in particular. Thus, the results of this project can impart knowledge of great importance both to the national and international food industry as well as the healthcare systems.

Detailed Description
-----------------
Using a randomised, cross-over design 12 healthy subjects and 12 subjects with type 2 diabetes will consume a test meal prior to a fat-rich meal. The test meals contain 2 different meal types; on where whey protein is consumed as a pre-meal and another where water is the pre-meal. In the second meal type whey protein is instead consumed as a part of the fat-rich meal. Blood samples are collected before consumption of the pre-meal and after consumption of the fat-rich isocaloric meal during 360 minutes. The fat-rich isocaloric meal is a breakfast containing 1043 kcal (15 E% protein, 65 E% fat and 20 E% carbohydrates). The main-meal is composed of white bread, rye bread, butter, cheese (45 %), salami, egg, bacon, milk (1.5 % fat) and coffee (decaffeinated) and should be consumed over 15 min. Visual Analog Scale (VAS) will be used for determination of subjective satiety feeling.

Official Title
-----------------
Whey Protein, Postprandial Lipemia and Cardiovascular Disease: Evaluation of the Effect of a Pre-meal of Whey Protein on Postprandial Lipiemia in Subjects With the Metabolic Syndrome and Type 2 Diabetes

Conditions
-----------------
Healthy, Type 2 Diabetes

Intervention / Treatment
-----------------
* Dietary Supplement: 20 g whey protein


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria - general: Weight stable for the last three month. BMI<40 Inclusion Criteria for subjects with type 2 diabetes: Diagnosed type 2 diabetes (HbA1c > 48 mmol/l) Stable dose of Metformin, Sulfonylurea (SU), insulin and SGLT inhibitors are accepted. Exclusion Criteria - general: Type 1 diabetes Type 2 diabetes (HbA1c ≥ 48 mmol/L) Fasting plasma triglycerides > 5.0 mmol/L Blood pressure > 160/100 mmHg Cardiovascular, liver, kidney or metabolic disease Corticosteroid treatment Pregnancy or lactation Alcohol or drug abuse Legal incapacity Exclusion Criteria for subjects with type 2 diabetes: Treatment with DPP-4 inhibitors, GLP-1 agonists and basal bolus insulin. Fasting blood glucose ≥ 14 mmol/l. Exclusion Criteria for healthy subjects: Prediabetes, defined from the WHO criteria (IGF ≥ 6.1 mmol/l).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20 g whey protein<br>20 g whey protein dissolved in 200 milliliter (mL) water is consumed as a pre-meal 15 min prior to the main meal. Additionally, 200 mL water is consumed as a part of the main meal. | Dietary Supplement: 20 g whey protein<br> <br> * Other names: Brand name: LACPRODAN® SP-9225 Instant (Lot nr.: D150214);|
| Placebo Comparator: Water<br>200 milliliter (mL) water consumed as pre-meal 15 min prior to the main meal. 20 g whey protein dissolved in 200 mL water is consumed as a part of the main meal. | Dietary Supplement: 20 g whey protein<br> <br> * Other names: Brand name: LACPRODAN® SP-9225 Instant (Lot nr.: D150214);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on triglyceride response of whey protein as pre-meal after a high-fat meal in healthy subjects and subjects with type 2 diabetes measured as incremental Area Under the Curve (iAUC -15 - 360 min). |  | Prior to the pre meal (-15 min), prior to the main meal (0 min) and 60, 90, 120, 180, 240 and 360 min post main meal | 
| Effect on apolipoprotein B48 of whey protein as pre-meal after a high-fat meal in healthy subjects and subjects with type 2 diabetes measured as incremental Area Under the Curve (iAUC -15 - 360 min). |  | Prior to the pre meal (-15 min), prior to the main meal (0 min) and 120, 240 and 360 min post main meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose responses measured as incremental Area Under the Curve (AUC -15 - 360 min) |  | Prior to the pre meal -15 min, -10 min, prior to the main meal (0 min) and 15, 30, 60, 90, 120, 240 and 360 min post main meal | 
| Insulin responses measured as incremental Area Under the Curve (AUC -15 - 360 min) |  | Prior to the pre meal -15 min, -10 min, prior to the main meal (0 min) and 15, 30, 60, 90, 120, 240 and 360 min post main meal | 
| Glucagon responses measured as incremental Area Under the Curve (AUC -15 - 360 min) |  | Prior to the pre meal -15 min, -10 min, prior to the main meal (0 min) and 15, 30, 60, 90, 120, 240 and 360 min post main meal | 
| Glucagon-like peptide 1 (GLP-1) responses measured as incremental Area Under the Curve (AUC -15 - 360 min) |  | Prior to the pre meal -15 min, -10 min, prior to the main meal (0 min) and 15, 30, 60, 90, 120, 240 and 360 min post main meal | 
| Gastric inhibitory peptide (GIP) responses measured as incremental Area Under the Curve (AUC -15 - 360 min). |  | Prior to the pre meal -15 min, -10 min, prior to the main meal (0 min) and 15, 30, 60, 90, 120, 240 and 360 min post main meal | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Whey proteins, Postprandial lipemia, Pre-meal, Type 2 diabetes