Clinical trial NCT04316429: The Impact of Consumption of Eggs in the Context of Plant-Based Diets on Endothelial Function, Diet Quality, and Cardio-Metabolic Risk Factors in Adults at Risk for Type 2 Diabetes
Official title: The Impact of Consumption of Eggs in the Context of Plant-Based Diets on
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Cardiovascular Diseases
Lead sponsor: Griffin Hospital
Sponsor class: OTHER
First posted: 2020-03-20
Enrollment: 35
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: To provide a sound basis for the statistical comparison of outcome measures for treatment assignments, participants will be randomized to 1 of 2 sequence permutations of an egg-included vegan diet and a vegan diet, which will begin after a 4-week run in phase. Each permutation will include a 6-week treatment phase, followed by a 4-week washout phase, followed by 6-week treatment phase (20 weeks total for each study participant, including the run-in phase).
Primary purpose: PREVENTION

Brief summary: Purpose To assess the impact of inclusion of 2 eggs daily for 6 weeks in an otherwise vegan diet compared to a vegan diet on cardio-metabolic risk and dietary pattern in adults at risk for type 2 diabetes.

Hypotheses In comparison with a vegan diet, the inclusion of 2 eggs daily in an otherwise vegan diet will improve or have neutral effects on endothelial function and other markers of cardio-metabolic risk in adults at risk for type 2 diabetes.

(2) In comparison with a vegan diet, the inclusion of 2 eggs daily in an otherwise vegan diet will improve diet quality and nutrient intake in adults at risk for type 2 diabetes.

(2) In comparison with a vegan diet, the inclusion of 2 eggs daily in an otherwise vegan diet will improve diet quality and nutrient intake in adults at risk for type 2 diabetes.

Detailed description: Specific Aims of the Proposed Project:

1. To assess the impact of inclusion of 2 eggs daily for 6 weeks in an otherwise vegan diet, compared to a vegan diet, on endothelial function in adults at risk for T2DM. Specifically, to demonstrate superior or neutral effects on endothelial function with the inclusion of eggs in the context of otherwise vegan diets.
2. To assess the impact of the inclusion of eggs daily for 6 weeks in an otherwise vegan diet, compared to a vegan diet, on dietary pattern and cardio-metabolic risk factors in adults at risk for T2DM. Specifically, to determine the effects on egg intake in the context of an otherwise vegan diet on diet quality and nutrient intake, lipid profile, blood pressure, insulin sensitivity and anthropometric measures.

Design:

Proposed is a randomized, single-blind, controlled, crossover trial designed with 2 treatment assignments (vegan diet plus eggs and vegan diet ) to compare the effects of 6 weeks of each treatment assignment on endothelial function, nutrient intake, diet quality, and cardio-metabolic risk factors in individuals at risk for T2DM. After a 4-week run-period of an ad libitum vegan diet, participants will be randomized to 1 of 2 possible sequence permutations and then undergo repeated measures following inclusion of 2 eggs per day in their otherwise vegan diet, or a vegan diet for 6 weeks, with a 4-week washout period between treatment assignments. The participants will continue their vegan diets during the 4-week washout period.

Background In the United States (U.S.), diabetes is a public health problem of epidemic proportions, affecting more than 30 million individuals. Only 23.1 million of these individuals are diagnosed. An estimated 84.1 million adults aged 18 years and older have prediabetes. Nearly 1 out 10 individuals with prediabetes is aware that he or she has this condition. Fifteen to thirty percent of individuals with prediabetes are likely to develop Type 2 diabetes mellitus (T2DM) within 5 years. The total medical costs, including lost work and wages, for individuals diagnosed with diabetes are estimated to be $245 billion. When compared with individuals without diabetes, individuals with diabetes have a medical cost that is more than two times higher. When compared with those without diabetes, the risk of death in individuals with diabetes is more than 50% higher. Between 90% and 95% of all diagnosed cases of diabetes are T2DM. The complications of diabetes include stroke, hypertension, cardiovascular disease (CVD), blindness, kidney disease, nervous system damage, limb amputations, and biochemical imbalances that can cause acute life-threatening events. \[1\] When compared with those without diabetes, the rates of cardiovascular mortality are 2 to 4 times higher among adults with diabetes.

Obese individuals are more than seven times more likely to develop T2DM when compared with healthy weight individuals. The cells become more resistant to insulin when there is more body fat. Increased insulin resistance contributes to high blood pressure, increased low density lipoprotein (LDL) cholesterol and triglycerides, and reduced levels of high-density lipoprotein (HDL) cholesterol. High blood insulin levels are associated with increased body fat. They disrupt normal metabolism of fats, increasing blood cholesterol and triglyceride levels; interfere with intercellular communication, including blood pressure-regulating signals; and stimulate the sympathetic nervous system, increasing the cardiac contractility and arterial resistance. Weight gain of as little as 10 pounds over 15 years could double an individual's insulin resistance and increase the risk of diabetes. When fat is primarily stored in the abdomen, the risk of diabetes is increased compared with when the fat is stored elsewhere. Abdominal fat wrap around organs such as the liver that play a vital role in glycemic control. Accumulation of fat around the liver blocks the action of insulin, which is needed to lower blood sugar; as a result, glucose accumulates in the blood stream.

Hyperglycemia has been linked to CVD. \[Hyperglycemia stimulates a pro-atherogenic phenotype in the vessel wall of endothelial cells, vascular smooth muscle cells, inflammatory cells, fibroblasts, and platelets, leading to an atherosclerotic response. Diets with a low glycemic load have been shown to improve serum lipid profiles, reduce C-reactive protein (CRP) levels, and aid in weight management. \[8\] Low glycemic index diets have been associated with higher levels of HDL cholesterol, reduced CRP concentrations, and decreased risk of developing diabetes and CVD. \[9\] While glycemic control remains the basis of diabetes care, the co-management of cardio-metabolic risk factors and prevention of long-term consequences are also recognized as essential to improve long-term survival.

Lifestyle intervention is the cornerstone for management and prevention of T2DM. Previous studies have shown that a reduction of as little as five to seven percent in body weight can lead to significantly improved cardio-metabolic risk factors among those at risk for T2DM. Patients with T2DM or at risk for T2DM are typically advised to consume foods with a low glycemic index (i.e., a relative ranking of carbohydrates in foods based on their impact on blood glucose levels). When steps are taken to ensure adequate consumption of nutrients, plant-based diets are recommended to reduce risk of T2DM. Without careful planning, it can be difficult for those consuming plant-based diets that exclude animal foods to consume optimal amounts of protein and other nutrients Vitamin B12 is present only in animal foods while iron, zinc, copper and selenium are more bioavailable when obtained from animal food sources. Eggs are rich in vitamins and minerals such as vitamin A, B2, B5, B12, phosphorus, selenium, iron and choline and contain the highest quality protein. Additionally, eggs are satiating and therefore have the potential to regulate calorie intake and reduce body weight. Hence, the inclusion of eggs in plant-based diets has the potential to improve diet quality by increasing intake of a variety of nutrients and ensuring the correct balance of nutritious foods. While some observational studies have identified associations between egg consumption and greater risk of T2DM, experimental trials in contrast have shown that eggs may improve insulin sensitivity and some cardio-metabolic risk factors in individuals with T2DM. In order to recommend eggs as part of a plant-based diet for this population, it is imperative to establish their effects on diet quality and cardio-metabolic health in the context of plant-based diets.

Eligibility criteria: Inclusion Criteria:

* 1) Male, 25-75 years or postmenopausal female 2) Non-smoker; 3) At risk for T2DM as defined by meeting at least one of the criteria listed:

  1. Metabolic syndrome, i.e. meet three out of five of the following criteria:

     1. blood pressure \>130/85 mmHg or currently taking antihypertensive medication;
     2. fasting plasma glucose (FPG) \>100 mg/dL (6.1 mmol/L);
     3. serum triglycerides level (TG)\>150 mg/dL (1.69 mmol/L);
     4. high-density lipoprotein (HDL) cholesterol \< 40 mg/dL (1.04 mmol/L) in men, and \< 50 mg/dL (1.29 mmol/L) in women;
     5. overweight (BMI ≥25kg/m²) with waist circumference of more than 40 inches (102 cm) for men and more than 35 inches (88 cm) for women.
  2. Fasting blood glucose \>100mg/dL and \<126mg/dL or hemoglobin A1C 5.7-6.4 %.

Exclusion Criteria:

* 1) Allergy to eggs; 2) Anticipated inability to complete the study protocol for any reason; 3) Current eating disorder; 4) Unstable use of lipid-lowering or antihypertensive medications (i.e., change in dose during the three months prior to enrollment) and/or unwilling to refrain from taking medication for 12 hours prior to endothelial function scanning; 5) Regular use of high doses of vitamin E (\>400IU/day) or vitamin C (\>500mg/day); fish oil, flaxseed oil, omega-3 fatty acid and/or fiber supplement, unless willing to discontinue supplementation for the study duration; 6) Use of insulin, glucose-sensitizing medication, or vasoactive medication (including glucocorticoids, antineoplastic agents, some psychoactive agents, or bronchodilators); 7) Unstable use of antidepressant medications (i.e., change in dose during the three months prior to enrollment; 8) Diagnosed diabetes; 9) Diagnosed sleep apnea; unless treated and have been stable with their medications for at least 3 months 10) Established cardiovascular disease (including symptomatic coronary artery disease (CAD), myocardial infarction, peripheral vascular disease, congestive heart failure, carotid stenosis); 11) Coagulopathy, known bleeding diathesis, or history of clinically significant hemorrhage; current use of warfarin or other regular use of anticoagulation; 12) Substance abuse (chronic alcoholism, other chemical dependency); 13) Any unstable medical condition that would limit the ability of a subject to participate fully in the trial (e.g., cancer, AIDS, tuberculosis, psychotic disorder); 14) For women: Use of hormone replacement therapy

Primary outcomes:
measure: Change in Endothelial Function (EF) Assessment:
timeFrame: 20 weeks
Secondary outcomes:
measure: Change in Diet quality: Automated Self-Administered 24-Hour Recall (ASA24)
timeFrame: 20 weeks
measure: Change in Serum Lipids
timeFrame: 20 weeks
measure: Change in Body composition
timeFrame: 20 weeks
measure: Change in Body weight
timeFrame: 20 weeks
measure: Waist circumference
timeFrame: 20 weeks
measure: Insulin Sensitivity
timeFrame: 20 weeks
measure: Office Blood Pressure
timeFrame: 20 weeks
measure: Change in Physical Activity
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Derby
country: United States
facility: Yale-Griffin Prevention Research Center
state: Connecticut
Study officials:
affiliation: Yale-Griffin Prevention Reserach Center
name: Valentine Yanchou Njike, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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