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

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, 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 improve glycemic control and cardiometabolic health in weight-stable adults with type 2 diabetes. The primary endpoint is glycemic control. Since changes in medication doses can skew the interpretation of glycemic outcomes, glycemic control will be assessed hierarchically (in descending order of importance) using (a) attainment of nondiabetic glycemia without medications (as a proxy for diabetes remission), (b) medication effect scores, (c) mean glucose during an oral glucose tolerance test, and (d) 24-hour mean glucose from continuous glucose monitoring. As secondary aims, this study will also test whether consuming a large amount of fructose in whole food form affects liver fat, pancreatic fat, and cardiovascular disease risk factors.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Behavioral: High-Fruit Diet

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Department of Nutrition Sciences, University of Alabamam at Birmingham

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 20-70 years old
• BMI ≤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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High-Fruit Diet; Whole fruit-rich diet (~50% of calories from whole fruit)

Behavioral: High-Fruit Diet; In this supervised controlled feeding study, participants will consume a diet rich in whole fruit. During the Ramp-Up Phase (Weeks 1-4), participants will gradually increase the amount of whole fruit they consume, eventually reaching 50% of calories from whole fruit. In the Main Phase (Weeks 5-12), 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 throughout the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diabetes Remission Rate	Percentage of patients who can maintain non-diabetic levels 24-hour mean glucose without the aid of pharmacotherapy at week 12	Change from baseline to week 12
Medication Effect Score (MES)	% (or percentage). This quantity estimates the percentage by which all anithyperglycemic medications taken by a patient would lower HbA1c levels (i.e., percent of glycated hemoglobin molecules). Higher values indicate a higher dose and/or potency of medications.	Change from baseline to Week 12
Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT)	mg/dl	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES	mg/dl	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Insulin During a 3-hour OGTT	mU/l	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Mean C-peptide During a 3-hour OGTT	ng/ml	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Mean Amplitude of Glycemic Excursions From CGM	mg/dl	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)"
Fasting Glucose	mg/dl	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
HbA1c	percentage	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Liver Fat (Intrahepatic Lipid)	Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Pancreatic Fat	Percentage as measured using MRS and 3-point M-Dixon MRI methods	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Systolic and Diastolic Blood Pressure	mm Hg	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Heart Rate	beats per minute	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Time-in-range Metrics From CGM	Time during which glucose levels are between 70 and 300 mg/dl	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Lipids	Fasting total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Insulin Sensitivity	Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model.	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Dynamic Beta-Cell Responsivity	Phi_dynamic during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi_dynamic is a measure of beta-cell responsiveness during first-phase insulin secretion. It is a dimensionless index (arbitrary units), where higher values denote greater insulin secretion.	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.
Static Beta-Cell Responsivity	Phi_static during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (which is a set of 5 coupled differential equations; see reference under Citations). Phi_static is a measure of beta-cell responsiveness during second-phase insulin secretion. The units of measure are min^-1, and higher values denote greater insulin secretion.	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints). Change from week 0 to 12 reported.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Weight	kg	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints); assessed weekly
Waist Circumference	cm	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Visceral Fat	Visceral fat as measured using MRI (kg)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Subcutaneous Abdominal Fat	Subcutaneous abdominal fat as measured using MRI (kg)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Gut Microbiome Diversity	Diversity metrics (i.e., alpha and beta diversity)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Gut Microbiome Composition	Taxonomic composition and abundances	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Preference and Sensitivity to Sweet Tastes	As measured on a 0-100 mm visual analog scale (VAS), using a Sweetness Taste Test	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Diet Satisfaction	As measured on a 0-100 mm visual analog scale (VAS)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
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
Food Cravings	As measured on five-point scales by the Food Craving Inventory-II	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Fruit Liking Visual Analog Scales	As measured by VAS on a 0-100 mm scale	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
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	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
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	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Depression	As measured on a 0-27 point scale by the Patient Health Questionnaire-9	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Mood States	As measured on a 5-point scale by the Profile of Mood States Short-Form	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)
Intervention Satisfaction and Feedback	As measured by qualitative exit interview	Week 12

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Courtney M. Peterson, Ph.D., University of Alabama at Birmingham

Publications and helpful links

General Publications

• Cobelli C, Dalla Man C, Toffolo G, Basu R, Vella A, Rizza R. The oral minimal model method. Diabetes. 2014 Apr;63(4):1203-13. doi: 10.2337/db13-1198.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2019
• Primary Completion (Actual): September 5, 2023
• Study Completion (Actual): September 5, 2023

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: type 2 diabetes; liver fat; glycemic control; diabetes remission; whole fruit; intrahepatic lipid; controlled feeding trial
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: IRB-300001719; P30DK079626 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No