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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03758742
• Other study ID #: IRB-300001719
• Status: Completed
• Phase: N/A
• Start date: September 10, 2019
• Est. completion date: February 5, 2024

Study information

• Verified date: March 2024
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: February 5, 2024
• Est. primary completion date: September 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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.

Locations

Country	Name	City	State
United States	Department of Nutrition Sciences, University of Alabamam at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body weight	kg	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Other	Waist circumference	cm	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Other	Pancreatic fat	Percentage as measured using MRS and 3-point M-Dixon MRI methods	Change from baseline to Weeks 4 and 12
Other	Visceral fat	kg as measured using MRI	Change from baseline to Weeks 4 and 12
Other	Subcutaneous abdominal fat	kg as measured using MRI	Change from baseline to Weeks 4 and 12
Other	Gut microbiome diversity	Diversity metrics (i.e., alpha and beta diversity)	Change from baseline to Weeks 4 and 12
Other	Gut microbiome composition	Taxonomic composition and abundances	Change from baseline to Weeks 4 and 12
Other	Transcriptome	Fold change in gene expression within blood cells (includes pathway analyses)	Change from baseline to Weeks 4 and 12
Other	Preference and sensitivity to sweet tastes	As measured on a 0-100 mm visual analog scale (VAS), using a Sweetness Taste Test	Change from baseline to Weeks 4 and 12
Other	Caloric intake	kcal/day as measured using 7-day food records	Change from baseline to Week 4 and follow-up Month 12
Other	Macronutrient composition	Percentage of calories as measured using 7-day food records	Change from baseline to Week 4 and follow-up Month 12
Other	Diet satisfaction	As measured on a 0-100 mm visual analog scale (VAS)	Change from baseline to Weeks 4 and 12
Other	Food intake	Percent intake of individual food categories as measured using 7-day food records	Change from baseline to Week 4 and follow-up Month 12
Other	Habitual fruit consumption	As estimated using a series of semi-quantitative food frequency questions from the Diet History Questionnaire	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Other	Food cravings	As measured on five-point scales by the Food Craving Inventory-II	Change from baseline to Weeks 4 and 12
Other	Fruit type preferences	As measured by VAS on a 0-100 mm scale	Change from baseline to Weeks 4 and 12
Other	Food attitudes and behaviors	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	Change from baseline to Weeks 4 and 12
Other	General health status	Healthy days (along various dimensions) as measured by the Centers for Disease Control and Prevention's (CDC) Health-Related Qualify of Life questionnaire	Change from baseline to Weeks 4 and 12
Other	Depression	As measured on a 0-27 point scale by the Patient Health Questionnaire-9	Change from baseline to Weeks 4 and 12
Other	Mood states	As measured on a 5-point scale by the Profile of Mood States Short-Form	Change from baseline to Weeks 4 and 12
Other	Intervention satisfaction and feedback	As measured by qualitative exit interview	Week 12
Primary	Diabetes remission rate	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.	Change from baseline (Week 0) to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	Diabetes medication usage	As quantified by the Medication Effect Score	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	Fasting glucose	mg/dl	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	HbA1c	percentage	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	2-hour glucose tolerance	mg/dl	Change from baseline to Weeks 4 and 12
Primary	Mean glucose during a 3-hour Oral Glucose Tolerance Test (OGTT)	mg/dl	Change from baseline to Weeks 4 and 12
Primary	Mean insulin during a 3-hour OGTT	mU/l	Change from baseline to Weeks 4 and 12
Primary	Mean C-peptide during a 3-hour OGTT	ng/ml	Change from baseline to Weeks 4 and 12
Primary	Fasting insulin	mU/l	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	Fasting C-peptide	ng/ml	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Primary	Insulin sensitivity	Insulin sensitivity (dl/kg/min/µU/ml) during a 3-hour OGTT, as measured by the Oral Minimal Model	Change from baseline to Weeks 4 and 12
Primary	Insulin secretion	Beta-cell responsivity index during a 3-hour OGTT, as measured by the Oral Minimal Model	Change from baseline to Weeks 4 and 12
Primary	Beta-cell function	Insulinogenic index as measured during the first 15 minutes of a 3-hour OGTT	Change from baseline to Weeks 4 and 12
Primary	Mean 24-hour glucose levels, peak glucose levels, and mean amplitude of glycemic excursions (MAGE), as measured using continuous glucose monitoring	mg/dl	Change from baseline to Weeks 4 and 12
Secondary	Intrahepatic lipid (liver fat)	Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI)	Change from baseline to Weeks 4 and 12
Secondary	Fasting lipids	Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Secondary	Systolic and diastolic blood pressure	mm Hg	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Secondary	Heart rate	beats per minute	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Secondary	Number of cardiovascular medications used	Number for each category of medication (e.g., anti-hypertensive medications)	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12
Secondary	Dosage of cardiovascular medications used	Dosages for each category of medication (e.g., anti-hypertensive medications)	Change from baseline to Weeks 4 and 12 and follow-up Months 6, 9, and 12