Dietary Oxysterols and β-Cell Function Among African Americans

Morehouse School of Medicine24 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Type 2 Diabetes

Interventions

Plant-based diet with no oxysterolsBEHAVIORAL

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.

Standard ADA Diet (SADA)BEHAVIORAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Participants must be: 1. HbA1c: 5.7% - 7.0%: This HbA1c range reflects mild to moderate β-cell dysfunction. 2. Self-identified AA: This group has higher rates of T2D than the general population. 3. Adults over18 years old: This age group is at higher risk of T2D. 4. Ability to read, understand and communicate effectively in English: All information about the study and instructions for the study protocol will be in English. 5. 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. 6. On stable medication dosages for the three months prior to recruitment: This is to avoid bias or confounding with new medications or dosages changes. 7. 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. 8. Mentally competent and able to follow the study protocol and provide informed consent 9. 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: 1. 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. 2. Be taking statin medications or any other cholesterol lowering drugs or supplements: These medications may artificially lower serum cholesterol and oxysterol levels. 3. 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. 4. 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. 5. 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. 6. 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: 7. 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.: 8. Be taking biotin supplements: This interferes with the test for fasting C-Peptide. 9. 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. 10. 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.

Locations (1)

Morehouse School of Medicine

Atlanta, Georgia, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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%.

Time frame: 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.

Time frame: 12 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 12 weeks

Central Contacts

Jennifer Rooke, MD, MPH

CONTACT

404-317-7268 jrooke@msm.edu

Data from ClinicalTrials.gov

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