Cardioprotective Activities Of Whole Eggs On Vascular Endothelial Function In Prediabetic Adults

Study Overview
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Brief Summary
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Cardiovascular disease (CVD) is largely a lifestyle-related condition that is the #1 killer of adults in the United States. Our work is aimed at understanding how short-term increases in blood sugar, like those that accompany eating a meal, affect blood vessel function and the risk of CVD. This research is aimed at understanding how meals composed of eggs affect short-term increases in blood sugar from eating, which are connected with increased risk of CVD. In particular, the investigators are trying to identify a specific meal composed of either whole eggs, egg yolks, or egg whites, that best reduces acute increases in blood sugar brought on by meals that consist of majority carbohydrate. At the same time, the investigators are trying to explore the protective affects that eggs may have on blood vessel function and the reduction of CVD risk.

Detailed Description
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Cardiovascular disease (CVD) is the leading cause of death in the United States [1]. The inability of your blood vessels to properly enlarge and shrink, known as vascular endothelial dysfunction (VED), is an early event leading to CVD and can be caused by postprandial hyperglycemia (PPH) [1] or short-term increases in blood sugar that occur after you have eaten. Although we do not know how this occurs, research shows that temporary increases in blood sugar impair the blood vessel's ability to properly enlarge and shrink. We also know that impaired vessel function is an early event leading to CVD and that research shows that short-term increases in blood sugar impair blood vessel function, even in healthy people [2]. Because high blood levels of cholesterol increase CVD risk, this has triggered flawed guidelines to restrict cholesterol in our diet [3], including limiting egg consumption. The misguided fear towards eating eggs has been routinely challenged by large-scale studies failing to associate eggs with heart disease risk [4-8]. Research shows that eggs improve the functioning of insulin to reduce blood sugar [9]. They also contain bioactive peptides that may attenuate oxidative stress [10-11]. This provides rationale for their study as a dietary strategy to reduce PPH and VED. Thus, the objective of this study is to define the potential benefits of eggs and its components (egg yolk and egg whites) on blood vessel health in adults with prediabetes.

Official Title
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Cardioprotective Activities Of Whole Eggs On Vascular Endothelial Function In Prediabetic Adults

Conditions
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Prediabetes, Cardiovascular Disease

Intervention / Treatment
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* Other: Glucose (100g)
* Other: Glucose (75g)
* Other: Whole Eggs
* Other: Egg Whites
* Other: Egg Yolks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fasting glucose 100-125 mg/dL, non-dietary supplement user, no medications affecting vasodilation, inflammation, or energy metabolism, no CVD, nonsmokers, individuals having blood pressure <130/85 mmHg and total cholesterol <240 mg/dL. Exclusion Criteria: unstable weight (±2 kg), vegetarian or egg allergy, alcohol intake >3 drinks/d or >10 drinks/wk), or ≥7 h/wk of aerobic activity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oral Glucose Tolerance Test<br>We will perform fasting measurements of flow-mediated dilation (FMD) using ultrasound, and draw a blood sample, prior to administration of the test meal. Following these baseline measurements, participants will ingest glucose (100 g). FMD will be performed intermittently post-ingestion at 30, 60, 90, 120, 150, and 180 minutes. Blood samples will be collected at 0 min (immediately prior to eating) and at 30, 60, 90, 120, 150, and 180 minutes following the ingestion of the meal. After each blood sample is obtained, the catheter will be flushed with saline in order to prevent the formation of clots and to minimize the likelihood of having to insert a needle again. Subjects will remain supine in a comfortable position for the entire duration of the test. | Other: Glucose (100g)<br>* Ingestion of glucose (100g)<br>|
| Experimental: Glucose with Whole Eggs<br>We will perform fasting measurements of flow-mediated dilation (FMD) using ultrasound, and draw a blood sample, prior to administration of the test meal. Following these baseline measurements, participants will ingest glucose (75 g) with 1.5 whole eggs (cooked). FMD will be performed intermittently post-ingestion at 30, 60, 90, 120, 150, and 180 minutes. Blood samples will be collected at 0 min (immediately prior to eating) and at 30, 60, 90, 120, 150, and 180 minutes following the ingestion of the meal. After each blood sample is obtained, the catheter will be flushed with saline in order to prevent the formation of clots and to minimize the likelihood of having to insert a needle again. Subjects will remain supine in a comfortable position for the entire duration of the test. | Other: Glucose (75g)<br>* Ingestion of glucose (75g)<br>Other: Whole Eggs<br>* Ingestion of 1.5 whole eggs<br>|
| Experimental: Glucose with Egg Whites<br>We will perform fasting measurements of flow-mediated dilation (FMD) using ultrasound, and draw a blood sample, prior to administration of the test meal. Following these baseline measurements, participants will ingest glucose (75 g) with 7 egg whites (cooked). FMD will be performed intermittently post-ingestion at 30, 60, 90, 120, 150, and 180 minutes. Blood samples will be collected at 0 min (immediately prior to eating) and at 30, 60, 90, 120, 150, and 180 minutes following the ingestion of the meal. After each blood sample is obtained, the catheter will be flushed with saline in order to prevent the formation of clots and to minimize the likelihood of having to insert a needle again. Subjects will remain supine in a comfortable position for the entire duration of the test. | Other: Glucose (75g)<br>* Ingestion of glucose (75g)<br>Other: Egg Whites<br>* Ingestion of 7 egg whites<br>|
| Experimental: Glucose with Egg Yolks<br>We will perform fasting measurements of flow-mediated dilation (FMD) using ultrasound, and draw a blood sample, prior to administration of the test meal. Following these baseline measurements, participants will ingest glucose (75 g) with 2 egg yolks (cooked). FMD will be performed intermittently post-ingestion at 30, 60, 90, 120, 150, and 180 minutes. Blood samples will be collected at 0 min (immediately prior to eating) and at 30, 60, 90, 120, 150, and 180 minutes following the ingestion of the meal. After each blood sample is obtained, the catheter will be flushed with saline in order to prevent the formation of clots and to minimize the likelihood of having to insert a needle again. Subjects will remain supine in a comfortable position for the entire duration of the test. | Other: Glucose (75g)<br>* Ingestion of glucose (75g)<br>Other: Egg Yolks<br>* Ingestion of 2 egg yolks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular Endothelial Function | Flow mediated dilation (FMD) evaluated on the basis as change from baseline to calculate FMD area under the curve from 0-180 min, i.e. i.e. Area Under the Curve (AUC) of change from baseline in FMD from 0 min to 180 min (i.e., AUC (FMD 0 min- 0 min, FMD 30 min-0 min, FMD 60 min-0 min, etc) | Area under the curve of brachial artery FMD for 3 hours (0, 30, 60, 90, 120 min) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose | Glucose concentrations evaluated on the basis as change from baseline to calculate glucose area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in glucose from 0 min to 180 min (i.e., AUC (glucose 0 min- 0 min, glucose 30 min-0 min, glucose 60 min-0 min, etc) | Area under the curve for plasma glucose for 3 hours (0, 30, 60, 90, 120 min) | 
| Oxidative Stress Biomarker (Malondialdehyde; MDA) | MDA concentrations evaluated on the basis as change from baseline to calculate MDAarea under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in MDA from 0 min to 180 min (i.e., AUC (MDA 0 min- 0 min, MDA 30 min-0 min, MDA 60 min-0 min, etc) | Area under curve of MDA for 3 hours (0, 30, 60, 90, 120, 150, 180 min) | 
| Insulin | Insulin concentrations evaluated on the basis as change from baseline to calculate insulin area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in insulin from 0 min to 180 min (i.e., AUC (Insulin 0 min- 0 min, insulin 30 min-0 min, insulin 60 min-0 min, etc) | Area under the curve for plasma insulin for 3 hours (0, 30, 60, 90, 120 min) | 
| Cholecystokinin (CCK) | CCK concentrations evaluated on the basis as change from baseline to calculate CCK area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in CCK from 0 min to 180 min (i.e., AUC (CCK 0 min- 0 min, CCK 30 min-0 min, CCK 60 min-0 min, etc) | Area under the curve for 3 hours (0, 30, 60, 90, 120 minutes) | 
| Methylglyoxal (MGO) | MGO concentrations evaluated on the basis as change from baseline to calculate MGO area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in MGO from 0 min to 180 min (i.e., AUC (MGO 0 min- 0 min, MGO 30 min-0 min, MGO 60 min-0 min, etc) | Area under the curve for methylglyoxal for 3 hours (0, 30, 60, 90, 120 min) | 
| 8-isoprostaglandin-F2a | 8-isoprostaglandin-F2a concentrations evaluated on the basis as change from baseline to calculate 8-isoprostaglandin-F2a area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in 8-isoprostaglandin-F2a from 0 min to 180 min (i.e., AUC (8-isoprostaglandin-F2a 0 min- 0 min, 8-isoprostaglandin-F2a 30 min-0 min, 8-isoprostaglandin-F2a 60 min-0 min, etc) | Area under the curve for 8-isoprostaglandin-F2a for 3 hours (0, 30, 60, 90, 120 min) | 
| Arachidonic Acid (AA) | Arachidonic acid concentrations evaluated on the basis as change from baseline to calculate arachidonic acid area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in arachidonic acid from 0 min to 180 min (i.e., AUC (arachidonic acid 0 min- 0 min, arachidonic acid 30 min-0 min, arachidonic acid 60 min-0 min, etc) | Area under the curve for arachidonic acid for 3 hours (0, 30, 60, 90, 120 min) | 
| 8-isoprostaglandin-F2a/Arachidonic Acid | 8-isoprostaglandin-F2a/arachidonic acid concentrations evaluated on the basis as change from baseline to calculate 8-isoprostaglandin-F2a/arachidonic acid area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in 8-isoprostaglandin-F2a/arachidonic acid from 0 min to 180 min (i.e., AUC (8-isoprostaglandin-F2a/arachidonic acid 0 min- 0 min, 8-isoprostaglandin-F2a/arachidonic acid 30 min-0 min, 8-isoprostaglandin-F2a/arachidonic acid 60 min-0 min, etc) | Area under the curve for 8-isoprostaglandin-F2a/arachidonic acid for 3 hours (0, 30, 60, 90, 120 min) | 
| Nitric Oxide Metabolites (Nitrites/Nitrates) (NOx) | Biomarker of nitric oxide homeostasis is based on the assessment of total nitrite and nitrate concentrations. Changes relative to baseline were used to calculate area under the curve of total nitric oxide metabolites from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in nitric oxide homeostasis from 0 min to 180 min (i.e., AUC (NOx 0 min- 0 min, NOx 30 min-0 min, NOx 60 min-0 min, etc) | Area under the curve for NOx for 3 hours (0, 30, 60, 90, 120 min) | 
| Arginine (Arg) | Arginine concentrations evaluated on the basis as change from baseline to calculate arginine area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in arginine from 0 min to 180 min (i.e., AUC (arginine 0 min- 0 min, arginine 30 min-0 min, arginine 60 min-0 min, etc) | Area under the curve for arginine for 3 hours (0, 30, 60, 90, 120 min) | 
| Asymmetric Dimethylarginine/Arginine (ADMA/Arg) | ADMA/Arg concentrations evaluated on the basis as change from baseline to calculate ADMA/Arg area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in ADMA/Arg from 0 min to 180 min (i.e., AUC (ADMA/Arg 0 min- 0 min, ADMA/Arg 30 min-0 min, ADMA/Arg 60 min-0 min, etc) | Area under the curve for ADMA/Arg for 3 hours (0, 30, 60, 90, 120 min) | 
| Symmetric Dimethylarginine/Arginine (SDMA/Arg) | SDMA/Arg concentrations evaluated on the basis as change from baseline to calculate SDMA/Arg area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in SDMA/Arg from 0 min to 180 min (i.e., AUC (SDMA/Arg 0 min- 0 min, SDMA/Arg 30 min-0 min, SDMA/Arg 60 min-0 min, etc) | Area under the curve for SDMA/Arg for 3 hours (0, 30, 60, 90, 120 min) | 
| Angiotensin-II | Angiotensin-II concentrations evaluated on the basis as change from baseline to calculate angiotensin-II area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in angiotensin-II from 0 min to 180 min (i.e., AUC (angiotensin-II 0 min- 0 min, angiotensin-II 30 min-0 min, angiotensin-II 60 min-0 min, etc) | Area under the curve for angiotensin-II for 3 hours (0, 30, 60, 90, 120 min) | 
| Endothelin-I | Endothelin-I concentrations evaluated on the basis as change from baseline to calculate endothelin-I area under the curve from 0-180 min, i.e. Area Under the Curve (AUC) of change from baseline in endothelin-I from 0 min to 180 min (i.e., AUC (endothelin-I 0 min- 0 min, endothelin-I 30 min-0 min, endothelin-I 60 min-0 min, etc) | Area under the curve for endothelin-I for 3 hours (0, 30, 60, 90, 120 min) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CVD, Hyperglycemia, Postprandial, Vascular Function