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

Not Applicable

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Behavioral: High-Fruit Diet

Registration Number: NCT03758742

Lead Sponsor: University of Alabama at Birmingham

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, 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High-Fruit Diet	High-Fruit Diet	Whole fruit-rich diet (\~50% of calories from whole fruit)

Primary Outcome Measures

Name	Time	Method
Medication Effect Score (MES)	Change from baseline to Week 12	% (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.
Mean Glucose During a 3-hour Oral Glucose Tolerance Test (OGTT)	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.	mg/dl
Diabetes Remission Rate	Change from baseline to week 12	Percentage of patients who can maintain non-diabetic levels 24-hour mean glucose without the aid of pharmacotherapy at week 12
Mean 24-hour Glucose Levels as Measured by Continuous Glucose Monitoring (CGM), Adjusted for Any Changes in Medication Doses Via the MES	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.	mg/dl

Secondary Outcome Measures

Name	Time	Method
Insulin Sensitivity	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.	Insulin sensitivity (dl/kg/min/μU/ml) during a 3-hour OGTT, as measured by the Oral Minimal Model.
Dynamic Beta-Cell Responsivity	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.	Phi_dynamic during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (a set of 5 differential equations. See Cobelli et al, Diabetes (2014)). Phi_dynamic is a measure of beta-cell responsiveness during first-phase insulin secretion. It is a dimensionless index (no units), where higher values denote greater insulin secretion.
Static Beta-Cell Responsivity	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.	Phi_static during a 3-hour OGTT, as measured by the Oral C-Peptide Minimal Model (a set of 5 differential equations. See Cobelli et al, Diabetes (2014)). Phi_static is a measure of beta-cell responsiveness during second-phase insulin secretion. Higher values denote greater insulin secretion.
Mean Insulin During a 3-hour OGTT	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.	mU/l
Mean C-peptide During a 3-hour OGTT	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.	ng/ml
Mean Amplitude of Glycemic Excursions From CGM	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)"	mg/dl
Fasting Glucose	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	mg/dl
HbA1c	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	percentage
Liver Fat (Intrahepatic Lipid)	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	Percentage as measured using Magnetic Resonance Spectroscopy (MRS) and 3-point M-Dixon Magnetic Resonance Imaging (MRI)
Pancreatic Fat	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	Percentage as measured using MRS and 3-point M-Dixon MRI methods
Systolic and Diastolic Blood Pressure	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	mm Hg
Heart Rate	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	beats per minute
Time-in-range Metrics From CGM	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	Time during which glucose levels are between 70 and 300 mg/dl
Lipids	Changes from weeks 0 to 12 (primary timepoint) and weeks 0 to 4 and 4 to 12 (secondary timepoints)	Fasting total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl)