Dietary Oxysterols and β-Cell Function Among African Americans

Study Overview
=================
Brief Summary
-----------------
African Americans (AAs) have a higher risk of developing type 2 diabetes than the general population. AAs are also more likely to eat foods that contain cholesterol oxides/oxysterols. Dietary oxysterols can harm the cells that produce insulin and decrease insulin production. This pilot study seeks to determine if removing dietary oxysterols with a plant-based diet will improve insulin production and decrease the risk of type 2 diabetes among AAs.

Detailed Description
-----------------
African Americans (AAs) have almost twice the incidence and prevalence of Type 2 diabetes (T2D) compared to the general population. T2D occurs when pancreatic β-cell dysfunction prevents secretion of sufficient insulin to overcome insulin resistance. While the causes of β-cell dysfunction are not fully understood, the role of cytotoxic oxidative stress is well documented. Serum oxysterols are biomarkers of oxidative stress. Oxysterols form endogenously or exogenously when cholesterol in food is exposed to light, heat, and processing. Dietary oxysterols are cytotoxic, they are absorbed and carried in the blood by lipoprotein carriers or circulate freely in serum. 7-Ketocholesterol (7-KC), the most common oxysterol in food and serum is a biomarker of cholesterol oxidation. High serum levels of 7-KC are associated with an increased risk of T2D. AAs who consume Southern dietary pattern foods such as fried and processed meats have a higher consumption of dietary oxysterols than the general population. Our central hypothesis is that the higher consumption of dietary oxysterols among AAs contributes to β-cell dysfunction and higher rates of T2D. The aim of this pilot study is to determine the effect of lowering dietary oxysterols on serum 7-KC and β-cell function among AAs with prediabetes and early T2D (HbA1c 5.7% - 7.0%). The expected outcome is that decreased exposure to dietary oxysterols will decrease serum oxysterols and β-cells oxidative stress which will improve β-cell function and glycemic control. The knowledge gained from this study may lead to improved T2D prevention and treatment strategies that may decrease the burden of T2D in all communities and eliminate the racial disparity among AAs.

Official Title
-----------------
Dietary Oxysterols and β-Cell Function Among African Americans

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Behavioral: Plant-based diet with no oxysterols
* Behavioral: Standard ADA Diet (SADA)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be: HbA1c: 5.7% - 7.0%: This HbA1c range reflects mild to moderate β-cell dysfunction. Self-identified AA: This group has higher rates of T2D than the general population. Adults over18 years old: This age group is at higher risk of T2D. Ability to read, understand and communicate effectively in English: All information about the study and instructions for the study protocol will be in English. Committed to eating the allocated study diet for 12 weeks: This is important to ensure that the study protocol is followed, and the data collected from participants is meaningful/valid. On stable medication dosages for the three months prior to recruitment: This is to avoid bias or confounding with new medications or dosages changes. Able to safely store a week's supply of prepared meals: Participants will receive packages of prepared food that has to stored and last them for the following week. Mentally competent and able to follow the study protocol and provide informed consent Currently eating the Standard American diet: The baseline diet of the participants will be assessed and correlated their baseline serum 7-KC levels and HOMA2 Index of β-cell function. Exclusion Criteria: Participants cannot: Be pregnant or lactating: Fetuses and breast-feeding infants are a protected vulnerable group. The risk of involving them in research must outweigh the benefits, Hormonal levels and other factors in pregnant and lactating woman may confound study results. Be taking statin medications or any other cholesterol lowering drugs or supplements: These medications may artificially lower serum cholesterol and oxysterol levels. Be currently on a vegan, vegetarian, or any type of plant-based diet for the 3 months prior to recruitment: Participants currently on these diets may not see significant changes on the dietary interventions of the study protocol. Be a current smoker: Smoking is a risk factor for oxidative stress - this could be an effect modifier or a confounding faction for this study. Be on medications or supplements to lower blood glucose or treat diabetes: This will be an effect modifier or confounding factor. We will not know the effect of the dietary intervention if the participants are also on medications for diabetes. Be status post blood transfusion in the previous 3 months: This will interfere with the test for HbA1c levels. This is one of our primary outcomes: Have a hemoglobin or any other blood disorder: This will interfere with the test for HBA1c which measures glycation of hemoglobin in red blood cells.: Be taking biotin supplements: This interferes with the test for fasting C-Peptide. Be on dialysis or have any stage of renal failure: Dialysis patients need special diets and more intense monitoring than is planned for the participants in this study. Have food allergies: Participants will be screened for food allergies. This is to prevent food sensitivities or adverse reactions to the prepared meals in the study.

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This pilot study is a longitudinal prospective randomized clinical trial with two parallel arms. Participants in both arms of the study will receive prepared meals based on ADA dietary guidelines for 12 weeks. One group will be given a plant-based ADA diet that contains no oxysterols (PB-ADAØ). The other group will be given the Standard ADA diet (SADA). The dietary 7-KC content of both diets will be estimated from oxysterol food composition databases. Sample meals from both groups will be analyzed to determine the 7-KC food content and the accuracy of the estimates.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A - Standard ADA dietary guidelines (SADA)<br>Participants in this group will be given prepared meals based on standard ADA dietary guidelines for 12 weeks. | Behavioral: Standard ADA Diet (SADA)<br>* This group will be given 3 prepared meals a day with macronutrient content: 60% of calories from carbohydrates, 15% protein, and 25% fat. Calories: 25 kcal/kg ideal body weight (IBW). The goal is weight maintenance, but weight loss may occur. 1-5% weight loss will be acceptable and not deemed a potential confounder. Participants will be screened for food allergies and intolerances prior to receiving their research diets. All meals will include culturally familiar foods to enhance adherence. The dietary intervention will be conducted over 4 3-month periods (12 months). Meals will be packaged labeled and distributed to participants once per week. Participants will consume their meals at home.<br>* Other names: ADA Diet;|
| Experimental: Group B - Plant Based ADA diet with no oxysterols (PB-ADAØ).<br>Participants in this group will be given prepared meals based on ADA guidelines but with no dietary cholesterol oxides/oxysterols - Plant-based ADA diet | Behavioral: Plant-based diet with no oxysterols<br>* This group will be given 3 prepared plant-based meals a day with macronutrient content: 60% of calories from carbohydrates, 15% protein, and 25% fat. Calories: 25 kcal/kg ideal body weight (IBW). The goal is weight maintenance, but weight loss may occur. 1-5% weight loss will be acceptable and not deemed a potential confounder. Participants will be screened for food allergies and intolerances prior to receiving their research diets. All meals will include culturally familiar foods to enhance adherence. The dietary intervention will be conducted over 4 3-month periods (12 months). Meals will be packaged labeled and distributed to participants once per week. Participants will consume their meals at home.<br>* Other names: Cholesterol Oxide-free plant-based diet;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Homeostasis Model Assessment of β-cell function (HOMA-B) Index | The HOMA-B index will be calculated using the HOMA2 Calculator with fasting C-peptide and fasting blood glucose levels. This study will compare the effect of the standard American Diabetes Association (ADA) diet that contains oxysterols and a plant-based ADA diet that does not contain oxysterols on the HOMA-B index of African Americans (AAs) with prediabetes and early diabetes. | 12 Weeks | 
| Glycated Hemoglobin (HbA1c) | HbA1c is a measure of glycemic control. This study will compare the effect of the standard ADA diet that contains oxysterols and a plant-based ADA diet without oxysterols on the HbA1c of AAs with HbA1c levels between 5.7% and 7.0%. | 12 weeksC-peptide levels are elevated in renal failure It is produced in equim C | 
| Serum 7-Ketocholesterol (7-KC) | 7-KC is one of the most abundant oxysterols in food and serum. This study will compare the effect of a standard ADA diet with oxysterols and a plant-based ADA diet without oxysterols on serum 7-KC levels. 7-KC will be measured by tandem liquid chromatography /mass spectrometry at the Emory Lipidomics lab. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index | This index will be calculated using the HOMA2 Calculator with fasting insulin and fasting blood glucose levels. The impact of the 2 different study diets on the HOMA-IR will be determined. | 12 Weeks | 
| Fasting Insulin | Insulin is a hormone produced by beta cells in the pancreas, it regulates serum glucose levels. The impact of the 2 different study diets on fasting insulin will be determined. | 12 weeks | 
| Fasting C-Peptide | C-peptide is a short chain of amino acids that is released as a byproduct of insulin production. It is produced in equimolar amounts as endogenous insulin but excreted at a more constant rate over a longer time. It is a sensitive, clinically validated assessment of of β-cell function. This study will measure the effect of the 2 study diets on fasting C-peptide. | 12 weeks | 
| Fasting Blood Glucose | Glucose is the main sugar found in blood. Elevated fasting blood glucose is a sign of diabetes. This study will measure the effects of the 2 study diets on fasting blood glucose. | 12 weeks | 
| Total cholesterol (TC) | TC is a measure of the total amount of cholesterol in blood. This study will determine the effect of the 2 study diets on serum TC levels. | 12 weeks | 
| High Density Lipoproteins (HDL) | HDL is the lipoprotein carrier that carries cholesterol from the cell to the liver to be excreted. This study will measure the effect of the 2 study diets on serum HDL levels. | 12 weeks | 
| Low Density Lipoproteins (LDL) | LDL is the liproprotein carrier that carries cholesterol from the liver to the cells of the body. This study will measure the effect of the 2 study diets on serum LDL levels. | 12 weeks | 
| Oxided Low Density Lipoproteins (Ox-LDL) | Ox-LDL form when LDLs carry cholesterol oxides/oxysterols. Ox-LDLs are cytotoxic and better indicators of cardiovascular risk than native LDL levels. This study will measure the effect of the 2 study diets on serum LDL levels. | 12 weeks | 
| Aspartate Amino Transferase (AST) | AST is an enzyme that is released from the liver when it is injured. It is an indicator of liver function. This study will measure the effect of the 2 study diets on AST levels. | 12 weeks | 
| Alanine Amino Transferase (ALT) | ALT is an enzyme that is released from the liver when it is injured. It is an indicator of liver function. This study will measure the effect of the 2 study diets on ALT levels. | 12 weeks | 
| Glomerular Filtration Rate (GFR) | GFR is an index of kidney function. This study will measure the effect of the 2 study diets on GFR. In addition, it is important to measure kidney function in this study because C-peptide levels are elevated in renal failure | 12 weeks | 
| Blood Urea Nitrogen (BUN) | BUN is a breakdown product of protein that is cleared from the blood by the kidneys. It is an indicator of kidney function. This study will measure the effect of the 2 study diets on BUN. | 12 weeks | 
| Creatinine | Creatinine is a by-product of normal muscle breakdown that is cleared from the blood by the kidneys. It is an indicator of kidney function. This study will measure the effect of the 2 study diets on serum creatinine levels. | 12 weeks | 
| White Blood Cell (WBC) Count | The WBC count is a measure of the number of WBCs the body. WBCs are immune cells and markers of inflammation. This study will measure the effect of the 2 study diets on WBC counts. | 12 weeks | 
| Hemoglobin (Hb) | Hb is a protein in red blood cells that carries oxygen from the lungs to the body. This study will measure the effect of the 2 study diets on Hb levels. In addition, it is important to know Hb levels because Hb abnormalities affect HbA1c levels. | 12 weeks | 
| Platelet Count | The platelet count is the number of platelets in blood. Platelets are involved in clotting, which is dysfunctional in diabetes. This study will measure the effect of the 2 study diets on platelet counts. | 12 weeks | 
| Calcium | This is measure of serum calcium levels. A plant-based diet may cause low calcium levels. This study will measure the effect of the 2 study diets on serum calcium levels. | 12 weeks | 
| Vitamin B12 | This is a measure of vitamin B-12 levels. People on plant-based diets may have lower vitamin B12 levels. This study will measure the effect of the 2 study diets on vitWBC amin B12 levels. | 12 weeks | 
| Blood pressure (BP) | BP is the pressure of circulating blood against the walls of blood vessels. It is an indicator of cardiovascular health. It will be measured at baseline, 6-weeks and post intervention. This study will measure the effect of the 2 study diets on BP. | 12 weeks | 
| Body composition using the Dual X-ray Absorptiometry (DEXA) Body Composition scan | The DEXA scan provides an analysis of body fat, muscle mass and bone density. This study will measure the effect of the 2 study diets on body composition. | 12 weeks | 
| Body Mass Index (BMI) | BMI is defined as the body weight divided by the square of the body height. This is expressed in units of kg/m². It will be used to classify study particpants according to body mass into underweight, normal, overweight or obese groups. This study will measure the effect of the 2 study diets on BMI. | 12 weeks | 
| Waist circumference (WC) | WC is the measurement taken around the abdomen at the level of the umbilicus (belly button). This measures abdominal obesity which may be a better indicator of health risk than BMI. This study will measure the effect of the 2 study diets on WC. | 12 weeks | 
| World Health Organization (WHO-5) Index of Well Being | The WHO-5 Well-Being Index is a short self-reported measure of current mental wellbeing. This study will measure the effect of the 2 study diets on this indicator of well being. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Beta-cell dysfunction oxysterols African Americans