Effect of Whole Fruit on Glycemic Control in Adults With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT03758742
• Recruitment Status: Recruiting
• First Posted: November 29, 2018
• Last Update Posted: September 18, 2019
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Courtney M Peterson, University of Alabama at Birmingham

Study Description

Brief Summary:

Diabetes costs the U.S. healthcare system more than any other disease, and nearly half of Americans will develop either diabetes or prediabetes in their lifetime. It is therefore critical to find new strategies to treat or reverse diabetes.

One such approach is adopting a healthy diet, which can dramatically improve blood sugar levels in adults with type 2 diabetes and even induce diabetes remission. Despite this, not much is known about which food groups are most effective at improving blood sugar levels in patients with diabetes.

Interestingly, of the various food groups that comprise the Mediterranean diet, epidemiologic data suggests that whole fruit may be one of the most efficacious at both preventing type 2 diabetes and improving blood sugar in patients with type 2 diabetes. However, few clinical trials have investigated the effects of whole fruit on blood sugar control. This study will therefore be the first to determine the effects of increasing whole fruit as a food group in type 2 diabetes patients. This supervised controlled feeding trial will test whether consuming a diet rich in whole fruit for 12 weeks can induce diabetes remission and can improve blood sugar, liver fat, and cardiovascular health in adults with type 2 diabetes. Thereafter, participants will be followed for up to one year. As a secondary aim, this study will also test whether consuming a large amount of fructose in whole food form negatively affects liver fat and cardiovascular health.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Behavioral: High-Fruit Diet	Not Applicable

Detailed Description:

Pre-registration notes: The primary endpoint is glycemic control, which will be analyzed hierarchically in descending order of importance as:

1. Diabetes remission rate (endpoint #1)
2. Medication effect score (endpoint #2)
3. Fasting glucose and HbA1c (endpoints #3-4)
4. Oral glucose tolerance test and continuous glucose monitoring measures (endpoints #5-14)

while the secondary endpoints (endpoints #15-20) will all be evaluated with equal importance.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 21 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Whole Fruit on Glycemic Control in Adults With Type 2 Diabetes
• Actual Study Start Date: September 10, 2019
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: May 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: High-Fruit Diet

Behavioral: High-Fruit Diet; Participants will consume a diet rich in whole fruit. During Phase I (Weeks 1-4; supervised controlled feeding), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In Phase II (Week 5-12; supervised controlled feeding), participants will consume a whole fruit-rich, eucaloric diet that provides 50% of calories in the form of whole fruit. The non-fruit portion of the diet will be styled as a Mediterranean Diet. Participants will be required to approximately keep their weight stable during Phases I and II. In the Follow-Up Phase (Months 4-12; free-living), participants will be instructed to continue consuming at least one-third of their diet as whole fruit and to make healthy food choices.

Outcome Measures

Primary Outcome Measures :

1. Diabetes remission rate [ Time Frame: Change from baseline (Week 0) to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   Remission rate will be measured in two ways. At the end of Phase II, it will be quantified as the percentage of patients who achieve non-diabetic levels of fasting glucose without the aid of any anti-hyperglycemic pharmacologic therapy or ongoing procedures.. During the Follow-up period, it will be quantified as the percentage of patients who achieve non-diabetic levels of both fasting glucose and HbA1c without the aid of any anti-hyperglycemic pharmacologic therapy or ongoing procedures.
2. Diabetes medication usage [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   As quantified by the Medication Effect Score
3. Fasting glucose [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   mg/dl
4. HbA1c [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   percentage
5. 2-hour glucose tolerance [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   mg/dl
6. Mean glucose during a 3-hour Oral Glucose Tolerance Test (OGTT) [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   mg/dl
7. Mean insulin during a 3-hour OGTT [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   mU/l
8. Mean C-peptide during a 3-hour OGTT [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   ng/ml
9. Fasting insulin [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   mU/l
10. Fasting C-peptide [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
    ng/ml
11. Insulin sensitivity [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral Minimal Model
12. Insulin secretion [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    Beta-cell responsivity index during a 3-hour OGTT, as measured by the Oral Minimal Model
13. Beta-cell function [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    Insulinogenic index as measured during the first 15 minutes of a 3-hour OGTT
14. Mean 24-hour glucose levels, peak glucose levels, and mean amplitude of glycemic excursions (MAGE), as measured using continuous glucose monitoring [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    mg/dl

Secondary Outcome Measures :

1. Intrahepatic lipid (liver fat) [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI)
2. Fasting lipids [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)
3. Systolic and diastolic blood pressure [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   mm Hg
4. Heart rate [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   beats per minute
5. Number of cardiovascular medications used [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   Number for each category of medication (e.g., anti-hypertensive medications)
6. Dosage of cardiovascular medications used [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   Dosages for each category of medication (e.g., anti-hypertensive medications)

Other Outcome Measures:

1. Body weight [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   kg
2. Waist circumference [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
   cm
3. Pancreatic fat [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   Percentage as measured using MRS and 3-point M-Dixon MRI methods
4. Visceral fat [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   kg as measured using MRI
5. Subcutaneous abdominal fat [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   kg as measured using MRI
6. Gut microbiome diversity [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   Diversity metrics (i.e., alpha and beta diversity)
7. Gut microbiome composition [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   Taxonomic composition and abundances
8. Transcriptome [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   Fold change in gene expression within blood cells (includes pathway analyses)
9. Preference and sensitivity to sweet tastes [ Time Frame: Change from baseline to Weeks 4 and 12 ]
   As measured on a 0-100 mm visual analog scale (VAS), using a Sweetness Taste Test
10. Caloric intake [ Time Frame: Change from baseline to Week 4 and follow-up Month 12 ]
    kcal/day as measured using 7-day food records
11. Macronutrient composition [ Time Frame: Change from baseline to Week 4 and follow-up Month 12 ]
    Percentage of calories as measured using 7-day food records
12. Diet satisfaction [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured on a 0-100 mm visual analog scale (VAS)
13. Food intake [ Time Frame: Change from baseline to Week 4 and follow-up Month 12 ]
    Percent intake of individual food categories as measured using 7-day food records
14. Habitual fruit consumption [ Time Frame: Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12 ]
    As estimated using a series of semi-quantitative food frequency questions from the Diet History Questionnaire
15. Food cravings [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured on five-point scales by the Food Craving Inventory-II
16. Fruit type preferences [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured by VAS on a 0-100 mm scale
17. Food attitudes and behaviors [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured by a modified version of the National Cancer Institute (NCI) 2007 Food Attitudes and Behaviors Survey, which covers constructs including attitudes and beliefs, fruit and vegetable consumption, eating behaviors, and food preferences
18. General health status [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    Healthy days (along various dimensions) as measured by the Centers for Disease Control and Prevention's (CDC) Health-Related Qualify of Life questionnaire
19. Depression [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured on a 0-27 point scale by the Patient Health Questionnaire-9
20. Mood states [ Time Frame: Change from baseline to Weeks 4 and 12 ]
    As measured on a 5-point scale by the Profile of Mood States Short-Form
21. Intervention satisfaction and feedback [ Time Frame: Week 12 ]
    As measured by qualitative exit interview

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 20-65 years old
• BMI between 27.0-45.0 kg/m^2
• First diagnosed with type 2 diabetes within the past 6 years
• HbA1c between 6.0-9.5%%

Exclusion Criteria:

• On insulin
• Diagnosis of diabetes before age 18
• Estimated glomerular filtration rate < 45 ml/min per 1.732 m^2
• Heart attack in the past 6 months or severe or unstable heart failure
• On weight loss medication
• Change in the dosage of a chronic medication that may affect study endpoints within the past 3 months
• Clinically significant laboratory abnormality (e.g. abnormal hemoglobin levels)
• Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones
• Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise safety or data validity
• Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years
• Lost or gained more than 5 kg of weight in the past 6 months
• Pregnant, planning to become pregnant in the next 12 months, or breastfeeding
• Major psychiatric condition that would affect the ability to participate in the study
• Not able to eat the provided study meals
• Behavioral factors or circumstances that may impede adhering to the dietary intervention
• Not able to do the MRI/MRS abdominal scan, such as due to claustrophobia, implanted metal objects, or a body girth of 60 cm or greater

Contacts and Locations

Contacts

Contact: Courtney M. Peterson, Ph.D.; 205-934-0122; cpeterso@uab.edu

Contact: Cody J. Hanick, M.S.; 205-934-5458; chanick@uab.edu

Locations

United States, Alabama

Department of Nutrition Sciences, University of Alabamam at Birmingham; Recruiting

Birmingham, Alabama, United States, 35233

Contact: Courtney Peterson, Ph.D. 205-934-0122 cpeterso@uab.edu

Contact: Cody Hanick, M.S. (262) 923-0672 chanick@uab.edu

Principal Investigator: Courtney Peterson, Ph.D.

Sub-Investigator: Cody Hanick, M.S.

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

• Principal Investigator: Courtney M. Peterson, Ph.D.; University of Alabama at Birmingham

More Information

• Responsible Party: Courtney M Peterson, Assistant Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03758742
• Other Study ID Numbers: IRB-300001719
• First Posted: November 29, 2018
• Last Update Posted: September 18, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Courtney M Peterson, University of Alabama at Birmingham:

diabetes; whole fruit; diabetes remission; glycemic control; liver fat; intrahepatic lipid; controlled feeding trial

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases